NLRP3
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Also known as AGTAVPRLAIIAVPFCASFCUNALP3PYPAF1MWSCLR1.1
Summary
NLRP3 (NLR family pyrin domain containing 3, HGNC:16400) is a protein-coding gene on chromosome 1q44, encoding NACHT, LRR and PYD domains-containing protein 3 (Q96P20). Sensor component of the NLRP3 inflammasome, which mediates inflammasome activation in response to defects in membrane integrity, leading to secretion of inflammatory cytokines IL1B and IL18 and pyroptosis.
This gene encodes a pyrin-like protein containing a pyrin domain, a nucleotide-binding site (NBS) domain, and a leucine-rich repeat (LRR) motif. This protein interacts with the apoptosis-associated speck-like protein PYCARD/ASC, which contains a caspase recruitment domain, and is a member of the NLRP3 inflammasome complex. This complex functions as an upstream activator of NF-kappaB signaling, and it plays a role in the regulation of inflammation, the immune response, and apoptosis. The SARS-CoV 3a protein, a transmembrane pore-forming viroporin, has been shown to activate the NLRP3 inflammasome via the formation of ion channels in macrophages. Mutations in this gene are associated with familial cold autoinflammatory syndrome (FCAS), Muckle-Wells syndrome (MWS), chronic infantile neurological cutaneous and articular (CINCA) syndrome, neonatal-onset multisystem inflammatory disease (NOMID), keratoendotheliitis fugax hereditarian, and deafness, autosomal dominant 34, with or without inflammation. Multiple alternatively spliced transcript variants encoding distinct isoforms have been identified for this gene. Alternative 5’ UTR structures are suggested by available data; however, insufficient evidence is available to determine if all of the represented 5’ UTR splice patterns are biologically valid.
Source: NCBI Gene 114548 — RefSeq curated summary.
At a glance
- Gene–disease (curated): cryopyrin-associated periodic syndrome (Definitive, GenCC) — +5 more curated relationships
- GWAS associations: 33
- Clinical variants (ClinVar): 1,254 total — 26 pathogenic, 28 likely-pathogenic
- Phenotypes (HPO): 109
- Druggable target: yes — 11 molecules with ChEMBL bioactivity
- MANE Select transcript:
NM_001243133
Identifiers
Gene identifiers
| Field | Value |
|---|---|
| HGNC ID | HGNC:16400 |
| Approved symbol | NLRP3 |
| Name | NLR family pyrin domain containing 3 |
| Location | 1q44 |
| Locus type | gene with protein product |
| Status | Approved |
| Aliases | AGTAVPRL, AII, AVP, FCAS, FCU, NALP3, PYPAF1, MWS, CLR1.1 |
| Ensembl gene | ENSG00000162711 |
| Ensembl biotype | protein_coding |
| OMIM | 606416 |
| Entrez | 114548 |
Gene structure
Transcript identifiers
Ensembl transcripts: 14 — 12 protein_coding, 1 retained_intron, 1 nonsense_mediated_decay
ENST00000336119, ENST00000348069, ENST00000366496, ENST00000391827, ENST00000391828, ENST00000474792, ENST00000532083, ENST00000642259, ENST00000643234, ENST00000697350, ENST00000697408, ENST00000898449, ENST00000898450, ENST00000959505
RefSeq mRNA: 6 — MANE Select: NM_001243133
NM_001079821, NM_001127461, NM_001127462, NM_001243133, NM_004895, NM_183395
CCDS: CCDS1632, CCDS1633, CCDS44346, CCDS44347
Canonical transcript exons
ENST00000336119 — 10 exons
| Exon | Start | End |
|---|---|---|
| ENSE00001125186 | 247435970 | 247436140 |
| ENSE00001778855 | 247418053 | 247419077 |
| ENSE00001871011 | 247448405 | 247448817 |
| ENSE00003901633 | 247416173 | 247416193 |
| ENSE00003970516 | 247434103 | 247434273 |
| ENSE00003970517 | 247443972 | 247444142 |
| ENSE00003970522 | 247423847 | 247425599 |
| ENSE00003970523 | 247423230 | 247423349 |
| ENSE00003970524 | 247429585 | 247429755 |
| ENSE00003970525 | 247444651 | 247444821 |
Expression profiles
Bgee: expression breadth ubiquitous, 172 present calls, max score 92.47.
FANTOM5 (CAGE): breadth broad, TPM avg 7.3612 / max 1270.8184, expressed in 376 samples.
FANTOM5 promoters (9 alternative TSS)
| Promoter ID | TPM avg | Samples expressed |
|---|---|---|
| 9587 | 5.7753 | 256 |
| 9586 | 1.4208 | 257 |
| 9588 | 0.0434 | 14 |
| 9589 | 0.0298 | 16 |
| 9593 | 0.0290 | 10 |
| 9592 | 0.0231 | 8 |
| 9594 | 0.0219 | 12 |
| 202040 | 0.0118 | 6 |
| 9590 | 0.0062 | 2 |
Top tissues by expression
289 total, by Bgee expression score (0-100, higher = more expressed):
| Tissue | Anatomy ID | Expression score | Quality |
|---|---|---|---|
| monocyte | CL:0000576 | 92.47 | gold quality |
| mononuclear cell | CL:0000842 | 91.72 | gold quality |
| leukocyte | CL:0000738 | 91.42 | gold quality |
| granulocyte | CL:0000094 | 86.88 | gold quality |
| blood | UBERON:0000178 | 83.96 | gold quality |
| bone marrow cell | CL:0002092 | 82.08 | gold quality |
| gall bladder | UBERON:0002110 | 76.13 | gold quality |
| bone marrow | UBERON:0002371 | 75.79 | gold quality |
| male germ line stem cell (sensu Vertebrata) in testis | CL:0000089 ∩ UBERON:0000473 | 75.71 | gold quality |
| right lung | UBERON:0002167 | 75.19 | gold quality |
| vermiform appendix | UBERON:0001154 | 74.52 | gold quality |
| upper lobe of left lung | UBERON:0008952 | 74.07 | gold quality |
| spleen | UBERON:0002106 | 73.68 | gold quality |
| upper lobe of lung | UBERON:0008948 | 72.38 | gold quality |
| omental fat pad | UBERON:0010414 | 71.66 | gold quality |
| peritoneum | UBERON:0002358 | 71.58 | gold quality |
| smooth muscle tissue | UBERON:0001135 | 71.28 | gold quality |
| right coronary artery | UBERON:0001625 | 70.70 | gold quality |
| adipose tissue of abdominal region | UBERON:0007808 | 70.18 | gold quality |
| C1 segment of cervical spinal cord | UBERON:0006469 | 70.08 | gold quality |
| caecum | UBERON:0001153 | 68.93 | gold quality |
| left uterine tube | UBERON:0001303 | 68.92 | gold quality |
| right frontal lobe | UBERON:0002810 | 68.38 | gold quality |
| rectum | UBERON:0001052 | 68.06 | gold quality |
| spinal cord | UBERON:0002240 | 67.24 | gold quality |
| mucosa of stomach | UBERON:0001199 | 67.15 | gold quality |
| prefrontal cortex | UBERON:0000451 | 67.04 | gold quality |
| left coronary artery | UBERON:0001626 | 66.53 | gold quality |
| lymph node | UBERON:0000029 | 66.23 | gold quality |
| cingulate cortex | UBERON:0003027 | 66.06 | gold quality |
Single-cell (SCXA)
Detected in 1 experiment(s), a significant marker in 1.
| Experiment | Marker? | Max mean expression |
|---|---|---|
| E-ANND-3 | no | 0.00 |
Regulation
Is transcription factor: no
Upstream regulators (CollecTRI, top): AP1, HESX1, IRF6, KLF5, NFKB, ZHX2
miRNA regulators (miRDB)
44 targeting NLRP3, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):
| miRNA | Max score | Avg score | miRNA target_count |
|---|---|---|---|
| HSA-MIR-1277-5P | 100.00 | 73.95 | 5056 |
| HSA-MIR-4282 | 99.99 | 75.36 | 6408 |
| HSA-MIR-223-3P | 99.99 | 70.14 | 1140 |
| HSA-MIR-3658 | 99.96 | 73.87 | 4379 |
| HSA-MIR-302E | 99.96 | 70.74 | 2669 |
| HSA-MIR-548AB | 99.95 | 71.31 | 3488 |
| HSA-MIR-559 | 99.95 | 72.28 | 3609 |
| HSA-MIR-548A-5P | 99.94 | 71.27 | 3482 |
| HSA-MIR-548AD-5P | 99.94 | 71.23 | 3502 |
| HSA-MIR-548AE-5P | 99.94 | 71.23 | 3502 |
| HSA-MIR-548AK | 99.94 | 71.24 | 3488 |
| HSA-MIR-548AM-5P | 99.94 | 71.24 | 3488 |
| HSA-MIR-548AP-5P | 99.94 | 71.14 | 3489 |
| HSA-MIR-548AQ-5P | 99.94 | 71.34 | 3426 |
| HSA-MIR-548AR-5P | 99.94 | 71.28 | 3515 |
| HSA-MIR-548AS-5P | 99.94 | 71.22 | 3482 |
| HSA-MIR-548AU-5P | 99.94 | 71.24 | 3488 |
| HSA-MIR-548AY-5P | 99.94 | 71.23 | 3502 |
| HSA-MIR-548B-5P | 99.94 | 71.23 | 3502 |
| HSA-MIR-548BB-5P | 99.94 | 71.27 | 3509 |
| HSA-MIR-548C-5P | 99.94 | 71.24 | 3488 |
| HSA-MIR-548D-5P | 99.94 | 71.23 | 3502 |
| HSA-MIR-548H-5P | 99.94 | 71.24 | 3488 |
| HSA-MIR-548I | 99.94 | 71.25 | 3481 |
| HSA-MIR-548J-5P | 99.94 | 71.14 | 3489 |
| HSA-MIR-548O-5P | 99.94 | 71.24 | 3488 |
| HSA-MIR-548W | 99.94 | 71.24 | 3488 |
| HSA-MIR-548Y | 99.94 | 71.28 | 3514 |
| HSA-MIR-22-3P | 99.93 | 68.13 | 917 |
| HSA-MIR-1305 | 99.91 | 71.43 | 3443 |
Literature-anchored findings (GeneRIF, showing 40)
- New mutations of CIAS1 that are responsible for Muckle-Wells syndrome and familial cold urticaria: a novel mutation underlies both syndromes. (PMID:11992256)
- Chronic infantile neurological cutaneous and articular syndrome is caused by mutations in CIAS1, a gene highly expressed in polymorphonuclear cells and chondrocytes. (PMID:12032915)
- Mutations in the NALP3/CIAS1/PYPAF1 gene are associated with familial cold urticaria and Muckle-Wells syndrome. (PMID:12355493)
- De novo CIAS1 mutations in neonatal-onset multisystem inflammatory disease. We found 6 heterozygous missense substitutions in CIAS1. Germline mutations. (PMID:12483741)
- a single heterozygous missense mutation (T1058C=L353P) in exon 3 of CIAS1 in all four families that is responsible for the large majority of FCAS cases (PMID:12522564)
- there is a cryopyrin signaling pathway activated through the induced proximity of ASC, which is negatively regulated by pyrin (PMID:12615073)
- mutated in CINCA syndrome (PMID:14630794)
- CIAS1/cryopyrin may act as a key regulator of inflammation, induced to dampen NF-kappa B-dependent proinflammatory signals. (PMID:14662828)
- cryopyrin disease-associated mutants are constitutively active and able to induce NF-kappaB activation and IL-1beta secretion at least in part by an increased ability to interact with ASC (PMID:15020601)
- NALP3 forms a protein complex that processes IL-1 beta in macrophages from a patient with the Muckle-Wells autoinflammatory disorder. (PMID:15030775)
- Missense mutations of CIAS1/PYPAF1/NALP3 gene occurred in 7 unrelated Spanish families with recurrent autoinflammatory diseases. (PMID:15593220)
- data suggest that both pyrin and cryopyrin are capable of assembling independent inflammasome complexes with ASC and procaspase-1, and activating caspase-1 via ASC oligomerization (PMID:16037825)
- Our approach yielded 26 candidate genes differentially expressed between patients (Osteoarthritis) and controls. BLP2 and CIAS1 seem to be trans-regulated, as the absence of allelic expression imbalances suggests. (PMID:16642435)
- Faf1 interacts with PYPAF1 and negatively regulates NF-kB activation induced by co-expression of PYAF1 and ASC. (PMID:17046979)
- monocytes undergo rapid cell death in a cathepsin B-dependent manner upon activation of cryopyrin, which is also a specific phenomenon induced by disease-associated mutation of CIAS1 (PMID:17164343)
- NALP 1 and 3 show distinct but separate expression profiles in human tissues suggesting a site-specific role in the inflammatory response (PMID:17164409)
- Anakinra therapy was well tolerated and has sustained efficacy on dermatologic and rheumatic manifestations in these patients with CIAS-1/NALP3 mutations. (PMID:17178985)
- identification of a novel CIAS1 mutation, F525C; mutation was shown to affect a highly conserved residue of the protein and to segregate with familial cold autoinflammatory syndrome throughout an extended family (PMID:17284928)
- most mutations mapped to an inner surface of the hexameric ring in the cryopyrin, consistent with the hypothesis that the mutations disrupt a closed form of cryopyrin, thus potentiating inflammasome assembly (PMID:17393462)
- The PRBC group had a significantly different expression profile included up-regulation of the cryopyrin protein. PRBCs activate inflammatory genes in circulating leukocytes. (PMID:17592301)
- study provides evidence that activation of NALP3, but not of the IPAF inflammasome, is blocked by inhibiting K(+) efflux from cells (PMID:17599094)
- A review of cryopyrinopathies caused by cryopyrin mutations. (PMID:17697637)
- results showed that the requirements of ATP stimulation for IL-1beta release observed in healthy individuals are bypassed in patients bearing CIAS1 mutations (PMID:17763411)
- functional expression of NLRP3 in osteoblasts provides potential mechanism underlying apoptotic cell death of these cells after challenge with intracellular bacterial pathogens & may be significant contributory factor to bone loss at sites of infection. (PMID:17907925)
- this report identifies cryopyrin as an important host regulator of programmed pathogen-induced necrosis in animals, a process we term pyronecrosis. (PMID:18005730)
- Effect of CIAS1 mutations in promoting necrosis-like cell death demonstrates that CIAS1 mosaicism plays an important role in mutation-negative Cias1-associated periodic syndrome. (PMID:18063752)
- The phenotype-genotype analysis of a Brazilian cohort of patients with cryopyrin-associated periodic syndromes (CAPS) is described. The following missense mutations were found in the cryopyrin gene, T436I, G755R, and C148Y. (PMID:18080732)
- We report a case of Muckle-Wells syndrome (MWS) caused by a novel mutation in the CIAS1/NALP3 gene. (PMID:18084703)
- Muckle-Wells syndrome (MWS) and familial cold autoinflammatory syndrome (FCAS) are rare periodic fevers associated with CIAS1 mutations. (PMID:18174231)
- The researchers found a mutation in exon 3 in the CIAS1 gene in a patient with the CINCA syndrome. (PMID:18175851)
- Mutations observed in a Finnish patient with familial cold autoinflammatory syndrome responsive to anakinra. (PMID:18189199)
- The NALP3 and TUCAN single-nucleotide polymorphisms may explain the increased IL-1beta levels and inflammatory symptoms observed, but further studies are needed to reveal a functional relationship. (PMID:18311798)
- These findings support the use of monogenic loci as candidates for investigating the genetic component of complex disease and provide preliminary evidence of association between SNPs in autoinflammatory genes and psoriatic JIA (PMID:18576390)
- in this report, there were confirmed three 5’-untranslated region splice forms with two separate transcriptional start sites, and identified potential promoter regions and six new DNA promoter variants. (PMID:18719602)
- Common variants in NLRP2 and NLRP3 genes are strong prognostic factors for the outcome of HLA-identical sibling allogeneic stem cell transplantation. (PMID:18772453)
- significant KPNA1-, NLRP1- and NLRP3-gene expression phenotypes associated with human genotypes of Crohn’s disease, Huntington’s disease and rheumatoid arthritis (PMID:19001869)
- These results suggest that the NLRP3 region is also implicated in the susceptibility of more common inflammatory diseases such as Crohn’s disease. (PMID:19098911)
- Genetic variations are associated with autoinflammatory disorders and increased susceptibility to microbial infection (PMID:19120479)
- promotes gout, an inflammatory disorder associated with hyperactivation of macrophages by uric acid from necrotic cells (PMID:19120481)
- P. gingivalis causes ASC- and NLRP3-dependent necrosis (PMID:19201894)
Cross-species orthologs
2 orthologs
| Organism | Symbol | Gene ID |
|---|---|---|
| mus_musculus | Nlrp3 | ENSMUSG00000032691 |
| rattus_norvegicus | Nlrp3 | ENSRNOG00000003170 |
Paralogs (20): NLRP2 (ENSG00000022556), NLRP1 (ENSG00000091592), NOD1 (ENSG00000106100), NLRC5 (ENSG00000140853), NLRP12 (ENSG00000142405), NLRP14 (ENSG00000158077), NLRP4 (ENSG00000160505), NLRX1 (ENSG00000160703), NOD2 (ENSG00000167207), NLRP7 (ENSG00000167634), NLRC3 (ENSG00000167984), NLRP5 (ENSG00000171487), NLRP13 (ENSG00000173572), NLRP6 (ENSG00000174885), CIITA (ENSG00000179583), NLRP8 (ENSG00000179709), NLRP11 (ENSG00000179873), NLRP10 (ENSG00000182261), NLRP9 (ENSG00000185792), PYDC2 (ENSG00000253548)
Protein
Protein identifiers
NACHT, LRR and PYD domains-containing protein 3 — Q96P20 (reviewed: Q96P20)
Alternative names: Angiotensin/vasopressin receptor AII/AVP-like, Caterpiller protein 1.1, Cold-induced autoinflammatory syndrome 1 protein, Cryopyrin, PYRIN-containing APAF1-like protein 1
All UniProt accessions (7): A0A2R8YEG7, A0A7I2PJH0, A0A7I2PMC6, A0A7I2PRX0, A0A7I2R3P8, A0A7I2UNQ2, A0A7I2YME5
UniProt curated annotations — full annotation on UniProt →
Function. Sensor component of the NLRP3 inflammasome, which mediates inflammasome activation in response to defects in membrane integrity, leading to secretion of inflammatory cytokines IL1B and IL18 and pyroptosis. In response to pathogens and other damage-associated signals that affect the integrity of membranes, initiates the formation of the inflammasome polymeric complex composed of NLRP3, CASP1 and PYCARD/ASC. Recruitment of pro-caspase-1 (proCASP1) to the NLRP3 inflammasome promotes caspase-1 (CASP1) activation, which subsequently cleaves and activates inflammatory cytokines IL1B and IL18 and gasdermin-D (GSDMD), promoting cytokine secretion and pyroptosis. Activation of NLRP3 inflammasome is also required for HMGB1 secretion; stimulating inflammatory responses. Involved in the homeostatic wound healing response to tissue injury, a multistep cascade that guides neutrophil migration to necrotic sites while avoiding collateral damage of healthy tissues. ATP released from necrotic cells triggers activation of NLRP3 inflammasome through P2RX7 signaling leading to neutrophil adhesion to the vascular endothelium close to the injury site. Under resting conditions, ADP-bound NLRP3 is autoinhibited. NLRP3 activation stimuli include extracellular ATP, nigericin, reactive oxygen species, crystals of monosodium urate or cholesterol, amyloid-beta fibers, environmental or industrial particles and nanoparticles, such as asbestos, silica, aluminum salts, cytosolic dsRNA, etc. Almost all stimuli trigger intracellular K(+) efflux. These stimuli lead to membrane perturbation and activation of NLRP3. Upon activation, NLRP3 is transported to microtubule organizing center (MTOC), where it is unlocked by NEK7, leading to its relocalization to dispersed trans-Golgi network (dTGN) vesicle membranes and formation of an active inflammasome complex. Associates with dTGN vesicle membranes by binding to phosphatidylinositol 4-phosphate (PtdIns4P). Shows ATPase activity. Independently of inflammasome activation, regulates the differentiation of T helper 2 (Th2) cells and has a role in Th2 cell-dependent asthma and tumor growth. During Th2 differentiation, required for optimal IRF4 binding to IL4 promoter and for IRF4-dependent IL4 transcription. Binds to the consensus DNA sequence 5’-GRRGGNRGAG-3’. May also participate in the transcription of IL5, IL13, GATA3, CCR3, CCR4 and MAF.
Subunit / interactions. Sensor component of NLRP3 inflammasomes; inflammasomes are supramolecular complexes that assemble in the cytosol in response to pathogens and other damage-associated signals and play critical roles in innate immunity and inflammation. The core of NLRP3 inflammasomes consists of a signal sensor component (NLRP3), an adapter (PYCARD/ASC), which recruits an effector pro-inflammatory caspase (CASP1 and, possibly, CASP4 and CASP5). Homodecamer; inactive NLRP3 forms homodecameric double-ring cages that hide pyrin domains within NACHT-LRR rings to avoid premature activation. Interacts (via pyrin domain) with PYCARD/ASC (via pyrin domain); interaction is direct. Interacts (via LRR repeat domain) with NEK7 (via N-terminus); the interaction is required for the formation of the complex NLRP3:PYCARD, oligomerization of PYCARD/ASC and activation of CASP1. Interacts (via LRR repeat domain) with NR4A1/Nur77 (via N-terminus); the interaction is direct, requires activation of NR4A1 by its ligands NBRE-containing dsDNA and lipopolysaccharide, and stimulates the association of NLRP3 with NEK7 for non-canonical NLRP3 inflammasome activation. Interacts with CARD8; leading to inhibit formation of the NLRP3 inflammasome. Interacts with MEFV; this interaction targets NLRP3 to degradation by autophagy, hence preventing excessive IL1B- and IL18-mediated inflammation. Interacts with EIF2AK2/PKR; this interaction requires EIF2AK2 activity, is accompanied by EIF2AK2 autophosphorylation and promotes inflammasome assembly in response to specific stimuli. Interacts with GBP5 (via DAPIN domain); this interaction promotes inflammasome assembly in response to microbial and soluble, but not crystalline, agents. Interacts with PML (isoform PML-1) (via the leucine-rich repeat (LRR) domain); PML-mediated increase in NLRP3 inflammasome activation does not depend upon this interaction. Interacts (via NACHT domain) with DHX33 (via DEAH box); NLRP3 activation in presence of cytosolic dsRNA is mediated by DHX33. Interacts (via NACHT and LRR domains) with ARRB2; this interaction is direct and inducible by polyunsaturated fatty acids (PUFAs). Interacts with PYDC5. Interacts (via NACHT domain) with DDX3X under both LPS-primed and inflammasome-activating conditions. Interacts with IRF4 (via the LRR domain); this interaction is direct and is required for optimal IRF4 binding to IL4 promoter and efficient IL4 transactivation during differentiation of Th2 helper T cells. Interacts with MAVS; promoting localization to mitochondria and activation of the NLRP3 inflammasome. Interacts with MARK4; promoting localization of NLRP3 to the microtubule organizing center (MTOC). Interacts with TRIM50; this interaction also promotes NLRP3 oligomerization and subsequent inflammasome activation. Interacts with IRGM; preventing NLRP3 inflammasome assembly and promoting NLRP3 degradation. Interacts (via KFERQ-like motifs) with HSPA8/HSC70; promoting NLRP3 degradation by the chaperone-mediated autophagy pathway. Interacts (via NACHT and LLR domains) with ABHD8; this interaction is enhanced in the presence of NLRP3 inflammasome inducers, such as ATP, nigericin, silica, or alum. Interaction with ABHD8 leads the recruitment of ZDHHC12, hence facilitating NLRP3 palmitoylation and degradation by the chaperone-mediated autophagy pathway (CMA), therefore attenuating NLRP3 inflammasome activation. (Microbial infection) Interacts with SARS coronavirus-2/SARS-CoV-2 N protein; the interaction is direct and promotes the binding of NLRP3 with PYCARD/ASC and facilitates NLRP3 inflammasome assembly. This interaction disrupts the association between NLRP3 and ABHD8, enhancing NLRP3 stability, ultimately leading to increased inflammasome activation. (Microbial infection) Interacts with M.pneumoniae CARDS toxin, which ADP-ribosylates NLRP3. (Microbial infection) Interacts with human cytomegalovirus protein US18; this interaction promotes inflammasome assembly.
Subcellular location. Cytoplasm. Cytosol. Inflammasome. Cytoskeleton. Microtubule organizing center. Golgi apparatus membrane. Endoplasmic reticulum. Mitochondrion. Secreted. Nucleus.
Tissue specificity. Predominantly expressed in macrophages. Also expressed in dendritic cells, B- and T-cells (at protein level). Expressed in LPS-treated granulocytes, but not in resting cells (at protein level). Expression in monocytes is very weak (at protein level). Expressed in stratified non-keratinizing squamous epithelium, including oral, esophageal and ectocervical mucosa and in the Hassall’s corpuscles in the thymus. Also, detected in the stratified epithelium covering the bladder and ureter (transitional mucosa) (at protein level). Expressed in lung epithelial cells (at protein level). Expressed in chondrocytes. Expressed at low levels in resting osteoblasts.
Post-translational modifications. Phosphorylation at Ser-198 by MAPK8/JNK1 increases inflammasome activation by promoting deubiquitination by BRCC3 and NLRP3 homooligomerization. Phosphorylation at Ser-806 by CSNK1A1 prevents inflammasome activation by preventing NEK7 recruitment. Phosphorylation at Ser-5 in the pyrin domain inhibits homomultimerization of NLRP3 and activation of the NLRP3 inflammasome: dephosphorylation by protein phosphatase 2A (PP2A) promotes assembly of the NLRP3 inflammasome. Phosphorylation at Ser-295 by PKD/PRKD1 promotes NLRP3 inflammasome assembly. Phosphorylation by ERK1/MAPK3 promotes NLRP3 inflammasome assembly. Phosphorylation by BTK (at Tyr-136, Tyr-140, Tyr-143 and Tyr-168) in the region that mediates binding to phosphatidylinositol phosphate, promotes relocalization of NLRP3 and assembly of the NLRP3 inflammasome. Phosphorylation at Tyr-861 inhibits NLRP3 inflammasome assembly: dephosphorylation by PTPN22 promotes inflammasome activation. Phosphorylated by LATS1 and LATS2 at Ser-265 following palmitoylation by ZDHHC1, promoting its relocalization to the microtubule organizing center (MTOC), where NLRP3 is activated by NEK7, leading to inflammasome assembly and activation. Ubiquitinated; undergoes both ‘Lys-48’- and ‘Lys-63’-linked polyubiquitination. Ubiquitination does not lead to degradation, but inhibits inflammasome activation. Deubiquitination is catalyzed by BRCC3 and associated with NLRP3 activation and inflammasome assembly. This process can be induced by the activation of Toll-like receptors (by LPS), through a non-transcriptional pathway dependent on the mitochondrial production of reactive oxygen species, and by ATP. Ubiquitinated by TRIM31 via ‘Lys-48’-linked ubiquitination, leading to its degradation by the proteasome. Ubiquitinated at Lys-689 by the SCF(FBXL2) complex, leading to its degradation by the proteasome. Ubiquitinated by TRIM35 via ’lys-48’ and ‘Lys-63’-linked ubiquitination leading to inhibition of NLRP3 inflammasome activation. Undergoes ‘Lys-27’-linked polyubiquitination by MARCHF5, leading to NLRP3-NEK7 complex formation and NLRP3 oligomerization. Palmitoylation by ZDHHC12 promotes NLRP3 degradation by the chaperone-mediated autophagy pathway (CMA) and therefore limits NLRP3 inflammasome activation. Following palmitoylation, HSPA8/HSC70 recognizes and binds the KFERQ-like motifs on NLRP3 and promotes NLRP3 recruitment to lysosomes, where it is degraded via the chaperone-mediated autophagy pathway in a LAMP2-dependent process. Palmitoylation at Cys-837 and Cys-838 by ZDHHC5 enhances its binding to NEK7 leading to inflammasome assembly and activation. Palmitoylation at Cys-130 and Cys-958 by ZDHHC1 facilitates phosphorylation at Ser-265 by LATS1 and LATS2, promoting its relocalization to the microtubule organizing center (MTOC), where NLRP3 is activated by NEK7, leading to inflammasome assembly and activation. Depalmitoylated by ABHD17A. Degraded via selective autophagy following interaction with IRGM. IRGM promotes NLRP3 recruitment to autophagosome membranes, promoting its SQSTM1/p62-dependent autophagy-dependent degradation. The disulfide bond in the pyrin domain might play a role in reactive oxygen species-mediated activation. (Microbial infection) ADP-ribosylated by M.pneumoniae CARDS toxin in vitro.
Disease relevance. Familial cold autoinflammatory syndrome 1 (FCAS1) [MIM:120100] A rare autosomal dominant systemic inflammatory disease characterized by recurrent episodes of maculopapular rash associated with arthralgias, myalgias, fever and chills, swelling of the extremities, and conjunctivitis after generalized exposure to cold. Rarely, some patients may also develop late-onset renal amyloidosis. The disease is caused by variants affecting the gene represented in this entry. Muckle-Wells syndrome (MWS) [MIM:191900] A hereditary periodic fever syndrome characterized by fever, chronic recurrent urticaria, arthralgias, progressive sensorineural deafness, and reactive renal amyloidosis. The disease may be severe if generalized reactive amyloidosis occurs. The disease is caused by variants affecting the gene represented in this entry. Chronic infantile neurologic cutaneous and articular syndrome (CINCA) [MIM:607115] Rare congenital inflammatory disorder characterized by a triad of neonatal onset of cutaneous symptoms, chronic meningitis, and joint manifestations with recurrent fever and inflammation. The disease is caused by variants affecting the gene represented in this entry. Keratoendothelitis fugax hereditaria (KEFH) [MIM:148200] An autosomal dominant corneal disease that periodically, and fleetingly, affects the corneal endothelium, stroma, and vision, eventually leading to central corneal stromal opacities in some patients. The disease is characterized by unilateral attacks of ocular pain, pericorneal injection, and photophobia. The acute symptoms vanish in 1-2 days but vision remains blurry for several weeks. The attacks start at the age of 3-12 years and can affect either eye. They generally decrease in frequency and get milder with age. The disease is caused by variants affecting the gene represented in this entry. Deafness, autosomal dominant, 34, with or without inflammation (DFNA34) [MIM:617772] A form of sensorineural hearing loss. Sensorineural deafness results from damage to the neural receptors of the inner ear, the nerve pathways to the brain, or the area of the brain that receives sound information. DFNA34 is a postlingual, slowly progressive form with variable severity and variable additional features. Some DFNA34 patients have autoinflammatory manifestations. The disease may be caused by variants affecting the gene represented in this entry.
Activity regulation. Under resting conditions, NLRP3 binds ADP and is autoinhibited. Inactive NLRP3 forms homodecameric double-ring cages that hide pyrin domains within NACHT-LRR rings to avoid premature activation. NLRP3 activation stimuli include extracellular ATP, nigericin, reactive oxygen species, crystals of monosodium urate or cholesterol, amyloid-beta fibers, environmental or industrial particles and nanoparticles, such as asbestos, silica, aluminum salts, cytosolic dsRNA, etc. Activated upon human coronavirus SARS-CoV-2 infection. Almost all stimuli trigger intracellular K(+) efflux. These stimuli lead to membrane perturbations that induce activation of NLRP3. Upon activation, NLRP3 is transported to microtubule organizing center (MTOC), where it is unlocked by NEK7, leading to its relocalization to dispersed trans-Golgi network (dTGN) vesicle membranes and recruitment of PYCARD/ASC for the formation of an active inflammasome complex. NEK7-activated NLRP3 forms a disk-shaped inflammasome. NLRP3 and PYCARD/ASC interact via their respective pyrin domains; interaction initiates speck formation (nucleation) which greatly enhances further addition of soluble PYCARD/ASC molecules to the speck in a prion-like polymerization process. Clustered PYCARD/ASC nucleates the formation of CASP1 filaments through the interaction of their respective CARD domains, acting as a platform for CASP1 polymerization and activation. Active CASP1 then processes IL1B and IL18 precursors, leading to the release of mature cytokines in the extracellular milieu and inflammatory response. NLRP3 inflammasome assembly is inhibited by IRGM, which impedes NLRP3 oligomerization. NLRP3 inflammasome is activated by cyclic di-AMP (c-di-AMP) and cyclic di-GMP (c-di-GMP), which enhance polymerization. NLRP3 inflammasome is inhibited by cyclic AMP (cAMP), which directly binds NLRP3; inhibition is relieved by calcium-sensing receptor CASR, which inhibits production of cAMP. Specifically inhibited by sulfonylurea MCC950 (also named CP-456,773, CRID3), a potent and specific small-molecule inhibitor of the NLRP3 inflammasome that acts by preventing ATP hydrolysis.
Domain organisation. The pyrin domain (also called DAPIN domain or PYD) is involved in PYCARD/ASC-binding. The FISNA domain is a critical mediator of NLRP3 conformational during NLRP3 activation. It becomes ordered in its key regions during activation to stabilize the active NACHT conformation and mediate most interactions in the NLRP3 disk. The LRR domain mediates the interaction with IRF4, PML, NEK7 and NR4A1/Nur77. The KFERQ-like motifs mediate binding to HSPA8/HSC70 following NLRP3 paylmitoylation by ZDHHC12.
Induction. By activators of Toll-like receptors, such as lipoteichoic acid (LTA) (TLR2), polyinosine-polycytidylic acid (poly(I:C), a synthetic analog of dsRNA) (TLR3) and bacterial lipopolysaccharides (LPS) (TLR4), and by TNF. Up-regulated in osteoblasts after exposure to invasive, but not invasion-defective, strains of Salmonella typhimurium (at protein level). In macrophages, up-regulated by endocannabinoid anandamide/AEA. (Microbial infection) In COVID-19 patient derived macrophages, expression is induced by SARS-CoV-2 spike protein, probably via TLR2 (at protein level).
Similarity. Belongs to the NLRP family.
Isoforms (6)
| UniProt ID | Names | Canonical? |
|---|---|---|
| Q96P20-1 | 2 | yes |
| Q96P20-2 | 1 | |
| Q96P20-3 | 3 | |
| Q96P20-4 | 4 | |
| Q96P20-5 | 5 | |
| Q96P20-6 | 6 |
RefSeq proteins (6): NP_001073289, NP_001120933, NP_001120934, NP_001230062, NP_004886, NP_899632 (=MANE)
Domains & families (InterPro)
| ID | Name | Type |
|---|---|---|
| IPR001611 | Leu-rich_rpt | Repeat |
| IPR004020 | DAPIN | Domain |
| IPR007111 | NACHT_NTPase | Domain |
| IPR011029 | DEATH-like_dom_sf | Homologous_superfamily |
| IPR027417 | P-loop_NTPase | Homologous_superfamily |
| IPR029495 | NACHT-assoc | Domain |
| IPR032675 | LRR_dom_sf | Homologous_superfamily |
| IPR041075 | NOD1/2_WH | Domain |
| IPR041267 | NLRP_HD2 | Domain |
| IPR050637 | NLRP_innate_immun_reg | Family |
Pfam: PF02758, PF05729, PF13516, PF14484, PF17776, PF17779
Catalyzed reactions (Rhea), 1 shown:
- ATP + H2O = ADP + phosphate + H(+) (RHEA:13065)
UniProt features (264 total): mutagenesis site 77, helix 49, strand 34, sequence variant 34, modified residue 20, repeat 9, sequence conflict 7, turn 6, cross-link 6, lipid moiety-binding region 5, short sequence motif 4, splice variant 4, domain 3, binding site 3, chain 1, region of interest 1, disulfide bond 1
Structure
Experimental structures (PDB)
24 structures.
| PDB | Method | Resolution (Å) |
|---|---|---|
| 3QF2 | X-RAY DIFFRACTION | 1.7 |
| 9GU4 | X-RAY DIFFRACTION | 2.7 |
| 8WSM | X-RAY DIFFRACTION | 2.7 |
| 9HG4 | X-RAY DIFFRACTION | 2.77 |
| 8RI2 | X-RAY DIFFRACTION | 2.8 |
| 7ALV | X-RAY DIFFRACTION | 2.83 |
| 9MGY | ELECTRON MICROSCOPY | 2.9 |
| 9SFG | X-RAY DIFFRACTION | 3.2 |
| 7VTP | ELECTRON MICROSCOPY | 3.23 |
| 8ERT | ELECTRON MICROSCOPY | 3.3 |
| 8ZEM | X-RAY DIFFRACTION | 3.32 |
| 8SWF | ELECTRON MICROSCOPY | 3.39 |
| 7ZGU | ELECTRON MICROSCOPY | 3.4 |
| 8EJ4 | ELECTRON MICROSCOPY | 3.4 |
| 8ETR | ELECTRON MICROSCOPY | 3.5 |
| 7PZD | ELECTRON MICROSCOPY | 3.6 |
| 9MIG | ELECTRON MICROSCOPY | 3.6 |
| 9DH3 | ELECTRON MICROSCOPY | 3.76 |
| 6NPY | ELECTRON MICROSCOPY | 3.8 |
| 7PZC | ELECTRON MICROSCOPY | 3.9 |
| 9MIE | ELECTRON MICROSCOPY | 3.93 |
| 8SXN | ELECTRON MICROSCOPY | 4.04 |
| 8SWK | ELECTRON MICROSCOPY | 4.32 |
| 2NAQ | SOLUTION NMR |
Predicted structure (AlphaFold)
| Model | pLDDT | Fraction very-high |
|---|---|---|
| AF-Q96P20-F1 | 81.16 | 0.47 |
Functional residue map
Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.
Ligand- & substrate-binding residues (3): 169; 226–234; 522
Post-translational modifications (31): 5, 13, 136, 140, 143, 161, 163, 168, 198, 198, 201, 265, 295, 334, 728, 735, 806, 861, 975, 1035 …
Disulfide bonds (1): 8–108
Mutagenesis-validated functional residues (77):
| Position | Phenotype |
|---|---|
| 24 | complete loss of pycard/asc filament nucleation; when associated with e-23. |
| 27 | impaired ability to homooligomerize into ordered polymers. complete loss of pycard/asc filament nucleation. |
| 31 | impaired ability to homooligomerize into ordered polymers. decreased pycard/asc filament nucleation. |
| 43 | impaired ability to homooligomerize into ordered polymers. |
| 43 | complete loss of pycard/asc filament nucleation. decreased pycard/asc filament nucleation. |
| 51 | does not affect ability to homooligomerize into ordered polymers. |
| 52 | decreased interaction with mapk4. |
| 64 | complete loss of pycard/asc filament nucleation. |
| 68 | does not affect ubiquitination by the scf(fbxl2) complex. |
| 73 | decreased ubiquitination by the scf(fbxl2) complex. |
| 77 | induces the formation of short but ordered homopolymers. |
| 80 | impaired ability to homooligomerize into ordered polymers. decreased pycard/asc filament nucleation. |
| 81 | impaired ability to homooligomerize into ordered polymers. decreased pycard/asc filament nucleation. |
| 82 | complete loss of pycard/asc filament nucleation. |
| 130 | decreased palmitoylation and activation of the nlrp3 inflammasome; when associated with a-958. |
| 136–143 | decreased phosphorylation by btk; when associated with f-168. |
| 143 | decreased ability to activate the nlrp3 inflammasome. |
| 147 | impaired ability to activate the nlrp3 inflammasome. |
| 152 | impaired ability to activate the nlrp3 inflammasome. |
| 155 | impaired ability to activate the nlrp3 inflammasome. |
| 157 | impaired ability to activate the nlrp3 inflammasome. |
| 166 | impaired ability to activate the nlrp3 inflammasome. |
| 168 | decreased phosphorylation by btk; when associated with 136-f–f-143. |
| 176 | impaired ability to activate the nlrp3 inflammasome. |
| 198 | abolished phosphorylation by mapk8/jnk1; decreased activation of the nlrp3 inflammasome. |
Function
Pathways and Gene Ontology
Reactome pathways
7 pathways
| ID | Pathway |
|---|---|
| R-HSA-5689901 | Metalloprotease DUBs |
| R-HSA-844456 | The NLRP3 inflammasome |
| R-HSA-9660826 | Purinergic signaling in leishmaniasis infection |
| R-HSA-9692916 | SARS-CoV-1 activates/modulates innate immune responses |
| R-HSA-9705671 | SARS-CoV-2 activates/modulates innate and adaptive immune responses |
| R-HSA-9707564 | Cytoprotection by HMOX1 |
| R-HSA-9860927 | Turbulent (oscillatory, disturbed) flow shear stress activates signaling by PIEZO1 and integrins in endothelial cells |
MSigDB gene sets: 911 (showing top):
GSE45365_NK_CELL_VS_CD8A_DC_DN, GOBP_REGULATION_OF_CELL_ACTIVATION, GOBP_RESPONSE_TO_ETHANOL, GOBP_GLUTAMATE_SECRETION, BUYTAERT_PHOTODYNAMIC_THERAPY_STRESS_DN, GOBP_CELLULAR_RESPONSE_TO_VIRUS, REACTOME_INNATE_IMMUNE_SYSTEM, GOBP_POSITIVE_REGULATION_OF_ADAPTIVE_IMMUNE_RESPONSE, GOBP_BEHAVIOR, GOBP_REGULATION_OF_ALPHA_BETA_T_CELL_ACTIVATION, GOBP_POSITIVE_REGULATION_OF_HEMOPOIESIS, GOBP_REGULATION_OF_BLOOD_PRESSURE, GOBP_RESPONSE_TO_ELECTRICAL_STIMULUS, GOBP_CIRCULATORY_SYSTEM_PROCESS, GOBP_NEGATIVE_REGULATION_OF_INTERLEUKIN_1_PRODUCTION
GO Biological Process (39): pattern recognition receptor signaling pathway (GO:0002221), negative regulation of acute inflammatory response (GO:0002674), positive regulation of type 2 immune response (GO:0002830), apoptotic process (GO:0006915), defense response (GO:0006952), inflammatory response (GO:0006954), signal transduction (GO:0007165), osmosensory signaling pathway (GO:0007231), detection of biotic stimulus (GO:0009595), negative regulation of interleukin-1 beta production (GO:0032691), positive regulation of interleukin-1 beta production (GO:0032731), positive regulation of interleukin-4 production (GO:0032753), NLRP3 inflammasome complex assembly (GO:0044546), innate immune response (GO:0045087), positive regulation of T-helper 2 cell differentiation (GO:0045630), positive regulation of transcription by RNA polymerase II (GO:0045944), regulation of inflammatory response (GO:0050727), negative regulation of inflammatory response (GO:0050728), positive regulation of inflammatory response (GO:0050729), obsolete positive regulation of NF-kappaB transcription factor activity (GO:0051092), protein homooligomerization (GO:0051260), protein maturation (GO:0051604), pyroptotic inflammatory response (GO:0070269), cellular response to lipopolysaccharide (GO:0071222), cellular response to virus (GO:0098586), negative regulation of non-canonical NF-kappaB signal transduction (GO:1901223), positive regulation of non-canonical NF-kappaB signal transduction (GO:1901224), positive regulation of T-helper 2 cell cytokine production (GO:2000553), immune system process (GO:0002376), acute inflammatory response (GO:0002526), positive regulation of cytokine production involved in immune response (GO:0002720), regulation of DNA-templated transcription (GO:0006355), response to virus (GO:0009615), positive regulation of interleukin-13 production (GO:0032736), positive regulation of interleukin-5 production (GO:0032754), defense response to Gram-positive bacterium (GO:0050830), defense response to virus (GO:0051607), cellular response to peptidoglycan (GO:0071224), positive regulation of T-helper 17 cell differentiation (GO:2000321)
GO Molecular Function (18): ATP binding (GO:0005524), ATP hydrolysis activity (GO:0016887), protein-macromolecule adaptor activity (GO:0030674), signaling adaptor activity (GO:0035591), identical protein binding (GO:0042802), peptidoglycan binding (GO:0042834), ADP binding (GO:0043531), sequence-specific DNA binding (GO:0043565), molecular adaptor activity (GO:0060090), phosphatidylinositol-4-phosphate binding (GO:0070273), DNA-binding transcription factor binding (GO:0140297), molecular sensor activity (GO:0140299), cysteine-type endopeptidase activator activity (GO:0140608), molecular condensate scaffold activity (GO:0140693), phosphatidylinositol phosphate binding (GO:1901981), nucleotide binding (GO:0000166), protein binding (GO:0005515), hydrolase activity (GO:0016787)
GO Cellular Component (15): Golgi membrane (GO:0000139), extracellular region (GO:0005576), nucleus (GO:0005634), cytoplasm (GO:0005737), mitochondrion (GO:0005739), endoplasmic reticulum (GO:0005783), microtubule organizing center (GO:0005815), cytosol (GO:0005829), membrane (GO:0016020), interphase microtubule organizing center (GO:0031021), NLRP3 inflammasome complex (GO:0072559), Golgi apparatus (GO:0005794), cytoskeleton (GO:0005856), endomembrane system (GO:0012505), canonical inflammasome complex (GO:0061702)
Reactome top-level categories
Rollup of top-7 pathways:
| Category | Pathways |
|---|---|
| Deubiquitination | 1 |
| Inflammasomes | 1 |
| Cell recruitment (pro-inflammatory response) | 1 |
| SARS-CoV-1-host interactions | 1 |
| SARS-CoV-2-host interactions | 1 |
| Cellular response to chemical stress | 1 |
| Response of endothelial cells to shear stress | 1 |
GO top-level categories
Rollup of top GO terms by namespace:
| Category | Terms |
|---|---|
| cellular anatomical structure | 6 |
| intracellular membrane-bounded organelle | 4 |
| cytoplasm | 4 |
| inflammatory response | 3 |
| interleukin-1 beta production | 2 |
| regulation of interleukin-1 beta production | 2 |
| regulation of inflammatory response | 2 |
| adenyl ribonucleotide binding | 2 |
| protein binding | 2 |
| protein-macromolecule adaptor activity | 2 |
| anion binding | 2 |
| binding | 2 |
| endomembrane system | 2 |
| innate immune response-activating signaling pathway | 1 |
| acute inflammatory response | 1 |
| regulation of acute inflammatory response | 1 |
| negative regulation of inflammatory response | 1 |
| regulation of type 2 immune response | 1 |
| type 2 immune response | 1 |
| positive regulation of immune response | 1 |
| programmed cell death | 1 |
| apoptotic signaling pathway | 1 |
| execution phase of apoptosis | 1 |
| response to stress | 1 |
| defense response | 1 |
| cell communication | 1 |
| cellular process | 1 |
| signaling | 1 |
| regulation of cellular process | 1 |
| cellular response to stimulus | 1 |
| intracellular signal transduction | 1 |
| cellular response to osmotic stress | 1 |
| response to biotic stimulus | 1 |
| detection of stimulus | 1 |
| negative regulation of interleukin-1 production | 1 |
| positive regulation of interleukin-1 production | 1 |
| positive regulation of cytokine production | 1 |
| interleukin-4 production | 1 |
| regulation of interleukin-4 production | 1 |
| canonical inflammasome complex assembly | 1 |
Protein interactions and networks
STRING
3440 interactions, top by confidence (×1000):
| Protein A | Protein B | Partner UniProt | Score |
|---|---|---|---|
| NLRP3 | PYCARD | Q9ULZ3 | 999 |
| NLRP3 | AIM2 | O14862 | 999 |
| NLRP3 | CASP1 | P29466 | 999 |
| NLRP3 | NLRC4 | Q9NPP4 | 999 |
| NLRP3 | TXNIP | Q9H3M7 | 995 |
| NLRP3 | NEK7 | Q8TDX7 | 994 |
| NLRP3 | MEFV | O15553 | 990 |
| NLRP3 | NLRP1 | Q9C000 | 986 |
| NLRP3 | NLRP6 | P59044 | 985 |
| NLRP3 | NLRP7 | Q8WX94 | 984 |
| NLRP3 | DHX33 | Q9H6R0 | 983 |
| NLRP3 | NLRP12 | P59046 | 983 |
| NLRP3 | MAVS | Q7Z434 | 983 |
| NLRP3 | CARD8 | Q9Y2G2 | 976 |
| NLRP3 | NAIP | Q13075 | 965 |
IntAct
93 interactions, top by confidence:
| A | B | Type | Score |
|---|---|---|---|
| NLRP3 | PYCARD | psi-mi:“MI:0407”(direct interaction) | 0.950 |
| PYCARD | NLRP3 | psi-mi:“MI:0915”(physical association) | 0.950 |
| NLRP3 | PYCARD | psi-mi:“MI:0915”(physical association) | 0.950 |
| NLRP3 | PYCARD | psi-mi:“MI:0403”(colocalization) | 0.950 |
| PYCARD | NLRP3 | psi-mi:“MI:0403”(colocalization) | 0.950 |
| PYCARD | NLRP3 | psi-mi:“MI:0407”(direct interaction) | 0.950 |
| PYCARD | CASP1 | psi-mi:“MI:0914”(association) | 0.860 |
| NLRP3 | NLRP3 | psi-mi:“MI:0915”(physical association) | 0.690 |
| NLRP3 | NLRP3 | psi-mi:“MI:0407”(direct interaction) | 0.690 |
| NLRP3 | NEK7 | psi-mi:“MI:0915”(physical association) | 0.680 |
| CARD8 | NLRP3 | psi-mi:“MI:0915”(physical association) | 0.640 |
| NLRP3 | CARD8 | psi-mi:“MI:0915”(physical association) | 0.640 |
| NLRP3 | CARD8 | psi-mi:“MI:0914”(association) | 0.640 |
BioGRID (264): NLRP3 (Affinity Capture-Western), MCFD2 (Co-fractionation), NLRP3 (Co-fractionation), NLRP3 (Co-fractionation), NLRP3 (Affinity Capture-Western), FBXL2 (Affinity Capture-Western), NLRP3 (Biochemical Activity), HIST1H1B (Affinity Capture-MS), HNRNPC (Affinity Capture-MS), RBBP7 (Affinity Capture-MS), SNRPB (Affinity Capture-MS), SPAST (Affinity Capture-MS), TOP1 (Affinity Capture-MS), LTBP4 (Affinity Capture-MS), SMARCA5 (Affinity Capture-MS)
ESM2 similar proteins: A1Z198, A6QLE5, B0FPE9, D4A523, D9I2F9, D9I2G1, D9I2G3, D9I2G4, D9I2H0, E9Q5G7, E9Q5R7, P59045, P59046, P59047, Q0GKD5, Q288C4, Q2LKU9, Q2LKV2, Q2LKV5, Q2LKW6, Q3TKR3, Q3UWY1, Q63035, Q647I9, Q66X01, Q66X03, Q66X05, Q66X19, Q66X22, Q6B966, Q7RTR0, Q7TPX8, Q86W24, Q86W25, Q86W26, Q86W28, Q8BU40, Q8BVP1, Q8C6J9, Q8CCN1
Diamond homologs: A0A386CAB9, A6QLE5, B0FPE9, D4A523, Q1MT80, Q2LKV2, Q86W26, Q8CCN1, Q8R4B8, Q96P20, Q9I9N6, A1Z198, A8Y3R9, D9I2F9, D9I2G1, D9I2G3, D9I2G4, D9I2H0, E9Q5R7, P10775, P13489, P29315, P59044, P59046, P59047, Q0GKD5, Q2LKU9, Q2LKV5, Q2LKW6, Q5RAV7, Q63035, Q6B966, Q86W24, Q86W25, Q8HXK9, Q8HZP9, Q91VI7, Q91WS2, Q9C000, Q9EPB4
SIGNOR signaling
20 interactions.
| A | Effect | B | Mechanism |
|---|---|---|---|
| KCNJ8 | “down-regulates activity” | NLRP3 | binding |
| FBXL2 | “down-regulates quantity by destabilization” | NLRP3 | binding |
| “Cullin 1-RBX1-Skp1” | “down-regulates quantity by destabilization” | NLRP3 | polyubiquitination |
| PTPN22 | “up-regulates activity” | NLRP3 | dephosphorylation |
| PAK1 | “up-regulates activity” | NLRP3 | phosphorylation |
| LYN | down-regulates | NLRP3 | phosphorylation |
| PELI2 | “up-regulates activity” | NLRP3 | ubiquitination |
| TRIM65 | “down-regulates activity” | NLRP3 | ubiquitination |
| TRIM31 | “down-regulates quantity by destabilization” | NLRP3 | ubiquitination |
| ARIH2 | “up-regulates activity” | NLRP3 | ubiquitination |
| PRKD1 | “up-regulates activity” | NLRP3 | phosphorylation |
| MicroRNA-223 | “down-regulates quantity by destabilization” | NLRP3 | “post transcriptional regulation” |
| MAPK8 | “up-regulates activity” | NLRP3 | phosphorylation |
| MINK1 | “up-regulates activity” | NLRP3 | phosphorylation |
| NLRP3 | “form complex” | “NLRP3 inflammasome” | binding |
| ROS | “up-regulates activity” | NLRP3 | |
| TLRs | “up-regulates quantity by expression” | NLRP3 | |
| PKA | “down-regulates activity” | NLRP3 | phosphorylation |
Enriched among interaction partners
Reactome pathways and GO biological processes over-represented among this gene’s 23 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.
Reactome pathways:
| Pathway | Partners | Fold | FDR |
|---|---|---|---|
| Viral Infection Pathways | 5 | 9.1× | 3e-03 |
| Infectious disease | 5 | 7.3× | 6e-03 |
GO biological processes:
| GO term | Partners | Fold | FDR |
|---|---|---|---|
| defense response to virus | 5 | 18.2× | 8e-04 |
Disease & clinical
Clinical variants and AI predictions
ClinVar
1254 variants total. Per-class counts are floors (≥ shown; pagination cap):
| Classification | Count (floor) |
|---|---|
| Pathogenic | 26 |
| Likely pathogenic | 28 |
| Uncertain significance | 626 |
| Likely benign | 305 |
| Benign | 69 |
Top pathogenic / likely-pathogenic (30)
| Variant ID | HGVS | Classification |
|---|---|---|
| 2029953 | NM_001243133.2(NLRP3):c.779_780delinsCG (p.Arg260Pro) | Pathogenic |
| 2109144 | NM_001243133.2(NLRP3):c.1305G>C (p.Lys435Asn) | Pathogenic |
| 2203018 | NM_001243133.2(NLRP3):c.2263G>A (p.Gly755Arg) | Pathogenic |
| 234301 | NM_001243133.2(NLRP3):c.1705G>A (p.Gly569Arg) | Pathogenic |
| 2691257 | NM_001243133.2(NLRP3):c.29G>T (p.Arg10Met) | Pathogenic |
| 3633876 | NM_001243133.2(NLRP3):c.1698C>G (p.Phe566Leu) | Pathogenic |
| 429285 | NM_001243133.2(NLRP3):c.1065A>C (p.Lys355Asn) | Pathogenic |
| 4374 | NM_001243133.2(NLRP3):c.778C>T (p.Arg260Ter) | Pathogenic |
| 4376 | NM_001243133.2(NLRP3):c.1718T>C (p.Phe573Ser) | Pathogenic |
| 4377 | NM_001243133.2(NLRP3):c.907G>A (p.Asp303Asn) | Pathogenic |
| 4378 | NM_001243133.2(NLRP3):c.926T>C (p.Phe309Ser) | Pathogenic |
| 4379 | NM_001243133.2(NLRP3):c.1058T>C (p.Leu353Pro) | Pathogenic |
| 643124 | NM_001243133.2(NLRP3):c.1976T>G (p.Met659Arg) | Pathogenic |
| 837881 | NM_001243133.2(NLRP3):c.905T>G (p.Phe302Cys) | Pathogenic |
| 849794 | NM_001243133.2(NLRP3):c.1217T>C (p.Met406Thr) | Pathogenic |
| 97909 | NM_001243133.2(NLRP3):c.1043C>T (p.Thr348Met) | Pathogenic |
| 97936 | NM_001243133.2(NLRP3):c.1568T>G (p.Phe523Cys) | Pathogenic |
| 97939 | NM_001243133.2(NLRP3):c.1573G>A (p.Glu525Lys) | Pathogenic |
| 97945 | NM_001243133.2(NLRP3):c.1706G>C (p.Gly569Ala) | Pathogenic |
| 97946 | NM_001243133.2(NLRP3):c.1709A>G (p.Tyr570Cys) | Pathogenic |
| 97979 | NM_001243133.2(NLRP3):c.907G>C (p.Asp303His) | Pathogenic |
| 97980 | NM_001243133.2(NLRP3):c.908A>G (p.Asp303Gly) | Pathogenic |
| 97981 | NM_001243133.2(NLRP3):c.910G>A (p.Glu304Lys) | Pathogenic |
| 97985 | NM_001243133.2(NLRP3):c.920G>T (p.Gly307Val) | Pathogenic |
| 97987 | NM_001243133.2(NLRP3):c.931G>A (p.Glu311Lys) | Pathogenic |
| 97992 | NM_001243133.2(NLRP3):c.977G>A (p.Gly326Glu) | Pathogenic |
| 1066319 | NM_001243133.2(NLRP3):c.1218G>A (p.Met406Ile) | Likely pathogenic |
| 1487108 | NM_001243133.2(NLRP3):c.1700A>C (p.Glu567Ala) | Likely pathogenic |
| 1694432 | NM_001243133.2(NLRP3):c.1562T>A (p.Met521Lys) | Likely pathogenic |
| 1694555 | NM_001243133.2(NLRP3):c.1690G>A (p.Gly564Ser) | Likely pathogenic |
SpliceAI
2115 predictions. Top by Δscore:
| Variant | Effect | Δscore |
|---|---|---|
| 1:247418746:T:A | acceptor_gain | 1.0000 |
| 1:247419073:GTGGG:G | donor_gain | 1.0000 |
| 1:247423228:A:AG | acceptor_gain | 1.0000 |
| 1:247423228:AG:A | acceptor_gain | 1.0000 |
| 1:247423229:G:GA | acceptor_gain | 1.0000 |
| 1:247423229:GG:G | acceptor_gain | 1.0000 |
| 1:247423229:GGT:G | acceptor_gain | 1.0000 |
| 1:247423229:GGTT:G | acceptor_gain | 1.0000 |
| 1:247423229:GGTTC:G | acceptor_gain | 1.0000 |
| 1:247423309:G:GT | donor_gain | 1.0000 |
| 1:247423345:GAAAG:G | donor_gain | 1.0000 |
| 1:247423350:GTA:G | donor_loss | 1.0000 |
| 1:247423351:T:G | donor_loss | 1.0000 |
| 1:247423845:A:AG | acceptor_gain | 1.0000 |
| 1:247423846:G:GG | acceptor_gain | 1.0000 |
| 1:247434093:T:A | acceptor_gain | 1.0000 |
| 1:247444143:G:GG | donor_gain | 1.0000 |
| 1:247444818:TGGGG:T | donor_loss | 1.0000 |
| 1:247444819:GGG:G | donor_gain | 1.0000 |
| 1:247444819:GGGGT:G | donor_loss | 1.0000 |
| 1:247444820:GG:G | donor_gain | 1.0000 |
| 1:247444820:GGG:G | donor_gain | 1.0000 |
| 1:247444820:GGGTG:G | donor_loss | 1.0000 |
| 1:247444821:GG:G | donor_gain | 1.0000 |
| 1:247444822:G:T | donor_loss | 1.0000 |
| 1:247444823:T:A | donor_loss | 1.0000 |
| 1:247448253:G:GT | donor_gain | 1.0000 |
| 20:3084550:AGTAC:A | donor_loss | 1.0000 |
| 20:3084551:GTA:G | donor_loss | 1.0000 |
| 20:3084552:TA:T | donor_loss | 1.0000 |
AlphaMissense
6881 scored. Top likely-pathogenic:
| Variant | Protein change | am_pathogenicity |
|---|---|---|
| 1:247424138:A:T | K232I | 0.998 |
| 1:247424141:C:T | T233I | 0.998 |
| 1:247424135:G:A | G231E | 0.997 |
| 1:247424119:G:A | G226R | 0.996 |
| 1:247424119:G:C | G226R | 0.996 |
| 1:247424119:G:T | G226W | 0.995 |
| 1:247424135:G:T | G231V | 0.995 |
| 1:247425178:T:C | F579L | 0.995 |
| 1:247425180:C:A | F579L | 0.995 |
| 1:247425180:C:G | F579L | 0.995 |
| 1:247424134:G:T | G231W | 0.994 |
| 1:247424170:T:A | W243R | 0.994 |
| 1:247424170:T:C | W243R | 0.994 |
| 1:247424678:C:G | P412R | 0.994 |
| 1:247424686:T:C | C415R | 0.994 |
| 1:247424700:C:G | C419W | 0.994 |
| 1:247424861:C:A | A473D | 0.994 |
| 1:247444052:T:C | L917P | 0.994 |
| 1:247424120:G:A | G226E | 0.993 |
| 1:247424129:G:A | G229E | 0.993 |
| 1:247424137:A:C | K232Q | 0.993 |
| 1:247424139:A:C | K232N | 0.993 |
| 1:247424139:A:T | K232N | 0.993 |
| 1:247424561:T:C | F373S | 0.993 |
| 1:247424668:T:C | C409R | 0.993 |
| 1:247424678:C:A | P412H | 0.993 |
| 1:247425001:T:C | F520L | 0.993 |
| 1:247425003:C:A | F520L | 0.993 |
| 1:247425003:C:G | F520L | 0.993 |
| 1:247424670:C:G | C409W | 0.992 |
dbSNP variants (sampled 300 via entrez): RS1000031952 (1:247449211 A>G), RS1000168734 (1:247430451 A>G), RS1000171339 (1:247419700 C>T), RS1000191329 (1:247446237 CAA>C), RS1000401898 (1:247421982 A>G), RS1000437849 (1:247435942 G>A), RS1000560026 (1:247426570 C>T), RS1000750378 (1:247435904 T>G), RS1000836078 (1:247422233 G>A), RS1000895302 (1:247420002 A>G), RS1000937968 (1:247437239 T>C), RS1000970524 (1:247437545 A>G), RS1001096949 (1:247431586 G>A), RS1001134473 (1:247442926 CTATT>C,CTATTTATT), RS1001145469 (1:247420722 A>C,G,T)
Disease associations
OMIM: gene MIM:606416 | disease phenotypes: MIM:120100, MIM:148200, MIM:191900, MIM:607115, MIM:617772, MIM:108010
GenCC curated gene-disease
| Disease | Classification | Inheritance |
|---|---|---|
| CINCA syndrome | Definitive | Autosomal dominant |
| cryopyrin-associated periodic syndrome | Definitive | Autosomal dominant |
| familial cold autoinflammatory syndrome | Definitive | Autosomal dominant |
| familial cold autoinflammatory syndrome 1 | Strong | Autosomal dominant |
| Muckle-Wells syndrome | Supportive | Autosomal dominant |
| keratitis fugax hereditaria | Limited | Autosomal dominant |
Mondo (18): familial cold autoinflammatory syndrome 1 (MONDO:0007349), keratitis fugax hereditaria (MONDO:0007849), Muckle-Wells syndrome (MONDO:0008633), CINCA syndrome (MONDO:0011776), cryopyrin-associated periodic syndrome (MONDO:0016168), hearing loss, autosomal dominant 34, with or without inflammation (MONDO:0033261), autoinflammatory syndrome (MONDO:0019751), cleft palate (MONDO:0016064), lung adenocarcinoma (MONDO:0005061), squamous cell carcinoma (MONDO:0005096), focal segmental glomerulosclerosis (MONDO:0100313), long COVID-19 (MONDO:0100233), arteriovenous malformations of the brain (MONDO:0007154), atypical hemolytic-uremic syndrome (MONDO:0016244), pericardial effusion (MONDO:0001370)
Orphanet (10): CINCA syndrome (Orphanet:1451), NLRP3-associated autoinflammatory disease (Orphanet:208650), Familial cold urticaria (Orphanet:47045), Muckle-Wells syndrome (Orphanet:575), Keratitis fugax hereditaria (Orphanet:647815), Autoinflammatory syndrome (Orphanet:93665), Cleft palate (Orphanet:2014), Brain arteriovenous malformation (Orphanet:46724), Atypical hemolytic uremic syndrome (Orphanet:2134), NON RARE IN EUROPE: Adenocarcinoma of the lung (Orphanet:415268)
HPO phenotypes
109 total (30 of 109 shown, HPO-id order):
| HPO | Term |
|---|---|
| HP:0000006 | Autosomal dominant inheritance |
| HP:0000078 | Abnormality of the genital system |
| HP:0000083 | Renal insufficiency |
| HP:0000100 | Nephrotic syndrome |
| HP:0000112 | Nephropathy |
| HP:0000174 | Abnormal palate morphology |
| HP:0000256 | Macrocephaly |
| HP:0000365 | Hearing impairment |
| HP:0000366 | Abnormality of the nose |
| HP:0000407 | Sensorineural hearing impairment |
| HP:0000408 | Progressive sensorineural hearing impairment |
| HP:0000491 | Keratitis |
| HP:0000501 | Glaucoma |
| HP:0000505 | Visual impairment |
| HP:0000509 | Conjunctivitis |
| HP:0000520 | Proptosis |
| HP:0000538 | Pseudopapilledema |
| HP:0000554 | Uveitis |
| HP:0000613 | Photophobia |
| HP:0000618 | Blindness |
| HP:0000622 | Blurred vision |
| HP:0000648 | Optic atrophy |
| HP:0000823 | Delayed puberty |
| HP:0000969 | Edema |
| HP:0000975 | Hyperhidrosis |
| HP:0000979 | Purpura |
| HP:0000988 | Skin rash |
| HP:0000989 | Pruritus |
| HP:0001004 | Lymphedema |
| HP:0001025 | Urticaria |
GWAS associations
33 associations (top):
| Study | Trait | p-value |
|---|---|---|
| GCST000366_4 | Fibrinogen | 1.000000e-08 |
| GCST000965_16 | C-reactive protein levels | 1.000000e-15 |
| GCST002060_15 | Word reading | 8.000000e-06 |
| GCST002147_17 | Fibrinogen | 1.000000e-19 |
| GCST003194_14 | Fibrinogen levels | 6.000000e-29 |
| GCST004063_87 | Waist circumference adjusted for body mass index | 9.000000e-13 |
| GCST004121_16 | Fibrinogen levels | 1.000000e-21 |
| GCST004122_33 | Fibrinogen levels | 1.000000e-20 |
| GCST004603_201 | Platelet count | 7.000000e-12 |
| GCST004610_38 | White blood cell count | 6.000000e-18 |
| GCST004613_6 | Sum neutrophil eosinophil counts | 3.000000e-19 |
| GCST004614_123 | Granulocyte count | 2.000000e-18 |
| GCST004620_104 | Sum basophil neutrophil counts | 2.000000e-18 |
| GCST004626_11 | Myeloid white cell count | 1.000000e-18 |
| GCST004629_18 | Neutrophil count | 3.000000e-19 |
| GCST004633_100 | Neutrophil percentage of white cells | 2.000000e-09 |
| GCST007614_12 | C-reactive protein levels | 4.000000e-21 |
| GCST007615_11 | C-reactive protein levels | 6.000000e-25 |
| GCST007615_65 | C-reactive protein levels | 9.000000e-24 |
| GCST007615_66 | C-reactive protein levels | 4.000000e-11 |
| GCST90002390_345 | Mean corpuscular hemoglobin | 2.000000e-09 |
| GCST90002394_109 | Monocyte percentage of white cells | 1.000000e-13 |
| GCST90002398_518 | Neutrophil count | 1.000000e-29 |
| GCST90002399_23 | Neutrophil percentage of white cells | 2.000000e-13 |
| GCST90002400_548 | Plateletcrit | 1.000000e-15 |
| GCST90002402_269 | Platelet count | 4.000000e-11 |
| GCST90002404_6 | Red cell distribution width | 4.000000e-09 |
| GCST90002407_208 | White blood cell count | 4.000000e-12 |
| GCST90002407_209 | White blood cell count | 4.000000e-31 |
| GCST90011898_34 | Alanine aminotransferase levels | 2.000000e-14 |
EFO canonical traits (15, from GWAS)
| EFO ID | Trait name |
|---|---|
| EFO:0004458 | C-reactive protein measurement |
| EFO:0005300 | word reading |
| EFO:0007789 | BMI-adjusted waist circumference |
| EFO:0004309 | platelet count |
| EFO:0004833 | neutrophil count |
| EFO:0004842 | eosinophil count |
| EFO:0007987 | granulocyte count |
| EFO:0005090 | basophil count |
| EFO:0007990 | neutrophil percentage of leukocytes |
| EFO:0004527 | mean corpuscular hemoglobin |
| EFO:0007989 | monocyte percentage of leukocytes |
| EFO:0007985 | platelet crit |
| EFO:0009188 | Red cell distribution width |
| EFO:0004736 | aspartate aminotransferase measurement |
| EFO:0004533 | alkaline phosphatase measurement |
MeSH disease descriptors (11)
| Descriptor | Name | Tree numbers |
|---|---|---|
| D065766 | Atypical Hemolytic Uremic Syndrome | C12.050.351.968.419.936.463.500; C12.200.777.419.936.463.500; C12.950.419.936.463.500; C15.378.050.141.610.500; C15.378.140.855.925.500.500; C15.378.243.937.925.500.500 |
| D002294 | Carcinoma, Squamous Cell | C04.557.470.200.400; C04.557.470.700.400 |
| D002972 | Cleft Palate | C05.500.460.185; C05.660.207.540.460.185; C07.320.440.185; C07.465.525.185; C07.650.500.460.185; C07.650.525.185; C16.131.621.207.540.460.185; C16.131.850.500.460.185; C16.131.850.525.185 |
| D056587 | Cryopyrin-Associated Periodic Syndromes | C16.320.382.500; C17.800.827.368.500; C17.800.862.945.533.500.500; C17.800.862.945.766.500; C20.543.480.904.533.500.500; C20.543.480.904.766.500; C23.550.291.500.360.500.500 |
| D005923 | Glomerulosclerosis, Focal Segmental | C12.050.351.968.419.570.363.640; C12.200.777.419.570.363.660; C12.950.419.570.363.640 |
| D034381 | Hearing Loss | C09.218.458.341; C10.597.751.418.341; C23.888.592.763.393.341 |
| D002538 | Intracranial Arteriovenous Malformations | C10.228.140.300.520; C10.500.190.500; C14.240.850.750.295; C14.240.850.875.500; C14.907.150.295; C14.907.253.560.400; C16.131.240.850.750.295; C16.131.240.850.875.500; C16.131.666.190.500 |
| D007674 | Kidney Diseases | C12.050.351.968.419; C12.200.777.419; C12.950.419 |
| D010490 | Pericardial Effusion | C14.280.695 |
| D000094024 | Post-Acute COVID-19 Syndrome | C01.748.610.763.500.500; C01.925.705.500.500; C01.925.782.600.550.200.163.500; C08.381.677.807.500.500; C08.730.610.763.500.500; C23.550.291.500.829.375 |
| C563650 | Keratitis Fugax Hereditaria (supp.) |
Drugs & pharmacology
Drug and pharmacology data
Is drug target: yes
ChEMBL targets (2): CHEMBL1741208 (SINGLE PROTEIN), CHEMBL6195683 (PROTEIN-PROTEIN INTERACTION)
Molecules with ChEMBL bioactivity
11 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 164,479 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).
| Molecule | Name | Phase | Patents |
|---|---|---|---|
| CHEMBL2355051 | CLOMIPHENE | 4 | 36 |
| CHEMBL472 | GLYBURIDE | 4 | 53,236 |
| CHEMBL140 | CURCUMIN | 3 | 93,882 |
| CHEMBL5219660 | JT-001 | 3 | 9 |
| CHEMBL1076347 | TRICLOCARBAN | 2 | 15,622 |
| CHEMBL236150 | CLIOXANIDE | 2 | 1,112 |
| CHEMBL3989943 | DAPANSUTRILE | 2 | 480 |
| CHEMBL5314548 | USNOFLAST | 2 | 11 |
| CHEMBL4650350 | INZOMELID | 1 | 64 |
| CHEMBL5095170 | BMS-986299 | 1 | 20 |
| CHEMBL5409389 | NT-0796 | 1 | 7 |
PharmGKB: 1 entry (VIP=true, CPIC=false)
PharmGKB variants
2 variants.
| Variant | Genes | Level | Score | #Clin annots | Drugs |
|---|---|---|---|---|---|
| rs10754558 | NLRP3 | 0.00 | 0 | ||
| rs4612666 | NLRP3 | 0.00 | 0 |
GtoPdb / IUPHAR curated pharmacology
(IUPHAR/BPS Guide to Pharmacology — expert-curated)
Target class: catalytic receptor — NOD-like receptor family
Most potent curated ligand interactions (15 total), top 15:
| Ligand | Action | Affinity | Parameter |
|---|---|---|---|
| NT-0796 | Inhibition | 9.49 | pIC50 |
| compound 17 [WO2024240153] | Inhibition | 9.0 | pIC50 |
| NLRP3 inhibitor 3 [PMID: 33255820] | Inhibition | 8.9 | pIC50 |
| NP3-742 | Inhibition | 8.22 | pIC50 |
| MCC950 | Inhibition | 8.0 | pIC50 |
| NT-0249 | Inhibition | 7.96 | pIC50 |
| GDC-2394 | Inhibition | 7.29 | pIC50 |
| oridonin | Inhibition | 7.28 | pKd |
| NDT-19795 | Inhibition | 7.18 | pIC50 |
| oridonin derivative 32 [PMID: 38751194] | Inhibition | 7.11 | pIC50 |
| compound 15z [PMID: 38029358] | Inhibition | 6.89 | pIC50 |
| emlenoflast | Inhibition | 6.85 | pIC50 |
| CP-424,174 | Inhibition | 6.59 | pIC50 |
| CY-09 | Inhibition | 6.3 | pKd |
| selnoflast | Inhibition | 6.0 | pIC50 |
Binding affinities (BindingDB)
320 measured of 646 human assays (655 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.
| Ligand | Measure | Value | Patent |
|---|---|---|---|
| 2-(4-cyclopropyl-2,6-dimethylphenyl)-6-(1,3-thiazol-4-yl)-5H-pyrazolo[3,4-d]pyrimidin-4-one | IC50 | 2 nM | US-20250114361: PYRAZOLOPYRIMIDINE COMPOUND AND PHARMACEUTICAL USE THEREOF |
| 2-(4-iodo-2,6-dimethylphenyl)-6-(1-methylpyrazol-3-yl)-5H-pyrazolo[3,4-d]pyrimidin-4-one | IC50 | 2.5 nM | US-20250114361: PYRAZOLOPYRIMIDINE COMPOUND AND PHARMACEUTICAL USE THEREOF |
| 2-[4-(1,1-difluoroethyl)-2,6-dimethylphenyl]-6-(1,3-thiazol-4-yl)-5H-pyrazolo[3,4-d]pyrimidin-4-one | IC50 | 3 nM | US-20250114361: PYRAZOLOPYRIMIDINE COMPOUND AND PHARMACEUTICAL USE THEREOF |
| 2-[4-(1-fluorocyclopropyl)-2,6-dimethylphenyl]-6-(1-methylpyrazol-3-yl)-5H-pyrazolo[3,4-d]pyrimidin-4-one | IC50 | 3.1 nM | US-20250114361: PYRAZOLOPYRIMIDINE COMPOUND AND PHARMACEUTICAL USE THEREOF |
| 2-(4-cyclopropyl-2,6-dimethylphenyl)-6-pyrimidin-4-yl-5H-pyrazolo[3,4-d]pyrimidin-4-one | IC50 | 4.3 nM | US-20250114361: PYRAZOLOPYRIMIDINE COMPOUND AND PHARMACEUTICAL USE THEREOF |
| 2-(4-cyclopropyl-2,6-dimethylphenyl)-6-(4-methyl-1,3-thiazol-2-yl)-5H-pyrazolo[3,4-d]pyrimidin-4-one | IC50 | 6 nM | US-20250114361: PYRAZOLOPYRIMIDINE COMPOUND AND PHARMACEUTICAL USE THEREOF |
| 2-[4-cyclopropyl-2-(methoxymethyl)-6-methylphenyl]-6-(1-methylpyrazol-3-yl)-5H-pyrazolo[3,4-d]pyrimidin-4-one | IC50 | 6.3 nM | US-20250114361: PYRAZOLOPYRIMIDINE COMPOUND AND PHARMACEUTICAL USE THEREOF |
| 2-(4-cyclopropyl-2,6-dimethylphenyl)-6-(1-methylpyrazol-4-yl)-5H-pyrazolo[3,4-d]pyrimidin-4-one | IC50 | 6.7 nM | US-20250114361: PYRAZOLOPYRIMIDINE COMPOUND AND PHARMACEUTICAL USE THEREOF |
| 2-(4-bromo-2,6-dimethylphenyl)-6-pyrimidin-4-yl-5H-pyrazolo[3,4-d]pyrimidin-4-one | IC50 | 7.8 nM | US-20250114361: PYRAZOLOPYRIMIDINE COMPOUND AND PHARMACEUTICAL USE THEREOF |
| 2-(4-cyclopropyl-2,6-dimethylphenyl)-6-(6,7-dihydro-4H-pyrazolo[5,1-c][1,4]oxazin-2-yl)-5H-pyrazolo[3,4-d]pyrimidin-4-one | IC50 | 9 nM | US-20250114361: PYRAZOLOPYRIMIDINE COMPOUND AND PHARMACEUTICAL USE THEREOF |
| 2-(4-cyclopropyl-2,6-dimethylphenyl)-6-(5,6-dihydro-4H-pyrrolo[2,1-e]pyrazol-2-yl)-5H-pyrazolo[3,4-d]pyrimidin-4-one | IC50 | 9 nM | US-20250114361: PYRAZOLOPYRIMIDINE COMPOUND AND PHARMACEUTICAL USE THEREOF |
| CHEMBL5439444 | IC50 | 11 nM | |
| 2-(4-cyclopropyl-2,6-dimethylphenyl)-6-pyridazin-4-yl-5H-pyrazolo[3,4-d]pyrimidin-4-one | IC50 | 11 nM | US-20250114361: PYRAZOLOPYRIMIDINE COMPOUND AND PHARMACEUTICAL USE THEREOF |
| CHEMBL5397618 | IC50 | 12 nM | |
| 2-(4-cyclopropyl-2,6-dimethylphenyl)-6-(1-methyltriazol-4-yl)-5H-pyrazolo[3,4-d]pyrimidin-4-one | IC50 | 12 nM | US-20250114361: PYRAZOLOPYRIMIDINE COMPOUND AND PHARMACEUTICAL USE THEREOF |
| 2-(4-bromo-2,6-dimethylphenyl)-6-(1-methyltriazol-4-yl)-5H-pyrazolo[3,4-d]pyrimidin-4-one | IC50 | 13 nM | US-20250114361: PYRAZOLOPYRIMIDINE COMPOUND AND PHARMACEUTICAL USE THEREOF |
| 2-[4-(1,1-difluoroethyl)-2,6-dimethylphenyl]-6-pyrimidin-4-yl-5H-pyrazolo[3,4-d]pyrimidin-4-one | IC50 | 14 nM | US-20250114361: PYRAZOLOPYRIMIDINE COMPOUND AND PHARMACEUTICAL USE THEREOF |
| 2-(4-cyclopropyl-2,6-dimethylphenyl)-6-(1-methylpyrazol-3-yl)-5H-pyrazolo[3,4-d]pyrimidin-4-one | IC50 | 15 nM | US-20250114361: PYRAZOLOPYRIMIDINE COMPOUND AND PHARMACEUTICAL USE THEREOF |
| 2-(4-bromo-2,6-dimethylphenyl)-6-pyridazin-4-yl-5H-pyrazolo[3,4-d]pyrimidin-4-one | IC50 | 15 nM | US-20250114361: PYRAZOLOPYRIMIDINE COMPOUND AND PHARMACEUTICAL USE THEREOF |
| 2-(4-bromo-2,6-dimethylphenyl)-6-(5-methyl-1,2-oxazol-3-yl)-5H-pyrazolo[3,4-d]pyrimidin-4-one | IC50 | 15 nM | US-20250114361: PYRAZOLOPYRIMIDINE COMPOUND AND PHARMACEUTICAL USE THEREOF |
| 2-(4-cyclopropyl-2,6-dimethylphenyl)-6-(4-fluoro-1-methylpyrazol-3-yl)-5H-pyrazolo[3,4-d]pyrimidin-4-one | IC50 | 15 nM | US-20250114361: PYRAZOLOPYRIMIDINE COMPOUND AND PHARMACEUTICAL USE THEREOF |
| 2-(4-cyclopropyl-2,6-dimethylphenyl)-6-(3-fluoro-4-pyridinyl)-5H-pyrazolo[3,4-d]pyrimidin-4-one | IC50 | 16 nM | US-20250114361: PYRAZOLOPYRIMIDINE COMPOUND AND PHARMACEUTICAL USE THEREOF |
| 2-(4-bromo-2,6-dimethylphenyl)-6-(1-methylpyrazol-4-yl)-5H-pyrazolo[3,4-d]pyrimidin-4-one | IC50 | 18 nM | US-20250114361: PYRAZOLOPYRIMIDINE COMPOUND AND PHARMACEUTICAL USE THEREOF |
| 2-(4-bromo-2,6-dimethylphenyl)-6-(1-methylpyrazol-3-yl)-5H-pyrazolo[3,4-d]pyrimidin-4-one | IC50 | 20 nM | US-20250114361: PYRAZOLOPYRIMIDINE COMPOUND AND PHARMACEUTICAL USE THEREOF |
| 2-(4-bromo-2,6-dimethylphenyl)-6-pyridazin-3-yl-5H-pyrazolo[3,4-d]pyrimidin-4-one | IC50 | 22 nM | US-20250114361: PYRAZOLOPYRIMIDINE COMPOUND AND PHARMACEUTICAL USE THEREOF |
| 2-[2,6-dimethyl-4-(trifluoromethyl)phenyl]-6-(3-fluoro-4-pyridinyl)-5H-pyrazolo[3,4-d]pyrimidin-4-one | IC50 | 22 nM | US-20250114361: PYRAZOLOPYRIMIDINE COMPOUND AND PHARMACEUTICAL USE THEREOF |
| 2-(4-cyclopropyl-2,6-dimethylphenyl)-6-(2-methylpyrazol-3-yl)-5H-pyrazolo[3,4-d]pyrimidin-4-one | IC50 | 23 nM | US-20250114361: PYRAZOLOPYRIMIDINE COMPOUND AND PHARMACEUTICAL USE THEREOF |
| 2-(4-cyclopropyl-2,6-dimethylphenyl)-6-[1-(2-methoxyethyl)pyrazol-3-yl]-5H-pyrazolo[3,4-d]pyrimidin-4-one | IC50 | 23 nM | US-20250114361: PYRAZOLOPYRIMIDINE COMPOUND AND PHARMACEUTICAL USE THEREOF |
| 2-(4-cyclopropyl-2,6-dimethylphenyl)-6-(1-methylimidazol-4-yl)-5H-pyrazolo[3,4-d]pyrimidin-4-one | IC50 | 23 nM | US-20250114361: PYRAZOLOPYRIMIDINE COMPOUND AND PHARMACEUTICAL USE THEREOF |
| 1-[amino-[4-(2-hydroxypropan-2-yl)-5-methylfuran-2-yl]-oxo-lambda6-sulfanylidene]-3-[(1R)-1-methyl-1,2,3,5,6,7-hexahydro-s-indacen-4-yl]urea | IC50 | 24 nM | US-11724992: Compounds and compositions for treating conditions associated with NLRP activity |
| 2-(4-bromo-2,6-dimethylphenyl)-6-(3-fluoro-4-pyridinyl)-5H-pyrazolo[3,4-d]pyrimidin-4-one | IC50 | 24 nM | US-20250114361: PYRAZOLOPYRIMIDINE COMPOUND AND PHARMACEUTICAL USE THEREOF |
| 2-(4-cyclopropyl-2,6-dimethylphenyl)-6-(6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazin-2-yl)-5H-pyrazolo[3,4-d]pyrimidin-4-one | IC50 | 24 nM | US-20250114361: PYRAZOLOPYRIMIDINE COMPOUND AND PHARMACEUTICAL USE THEREOF |
| 2-(4-bromo-2,6-dimethylphenyl)-6-(2-methoxypyrimidin-4-yl)-5H-pyrazolo[3,4-d]pyrimidin-4-one | IC50 | 27 nM | US-20250114361: PYRAZOLOPYRIMIDINE COMPOUND AND PHARMACEUTICAL USE THEREOF |
| 2-(4-cyclopropyl-2,6-dimethylphenyl)-6-(1H-pyrazol-5-yl)-5H-pyrazolo[3,4-d]pyrimidin-4-one | IC50 | 29 nM | US-20250114361: PYRAZOLOPYRIMIDINE COMPOUND AND PHARMACEUTICAL USE THEREOF |
| 2-[2,6-dimethyl-4-(1,1,2,2,2-pentafluoroethyl)phenyl]-6-(1-methylpyrazol-3-yl)-5H-pyrazolo[3,4-d]pyrimidin-4-one | IC50 | 33 nM | US-20250114361: PYRAZOLOPYRIMIDINE COMPOUND AND PHARMACEUTICAL USE THEREOF |
| 2-(6-chloro-2,3-dihydro-1H-inden-5-yl)-6-(1-methylpyrazol-3-yl)-5H-pyrazolo[3,4-d]pyrimidin-4-one | IC50 | 34 nM | US-20250114361: PYRAZOLOPYRIMIDINE COMPOUND AND PHARMACEUTICAL USE THEREOF |
| 2-(4-bromo-2,6-dimethylphenyl)-6-(4-fluoro-1-methylpyrazol-3-yl)-5H-pyrazolo[3,4-d]pyrimidin-4-one | IC50 | 36 nM | US-20250114361: PYRAZOLOPYRIMIDINE COMPOUND AND PHARMACEUTICAL USE THEREOF |
| 2-[4-cyclopropyl-2-(hydroxymethyl)-6-methylphenyl]-6-(1-methylpyrazol-3-yl)-5H-pyrazolo[3,4-d]pyrimidin-4-one | IC50 | 37 nM | US-20250114361: PYRAZOLOPYRIMIDINE COMPOUND AND PHARMACEUTICAL USE THEREOF |
| 2-(4-bromo-2,6-dimethylphenyl)-6-(1-ethylpyrazol-3-yl)-5H-pyrazolo[3,4-d]pyrimidin-4-one | IC50 | 40 nM | US-20250114361: PYRAZOLOPYRIMIDINE COMPOUND AND PHARMACEUTICAL USE THEREOF |
| 2-[4-(1,1-difluoroethyl)-2,6-dimethylphenyl]-6-(1-methylimidazol-4-yl)-5H-pyrazolo[3,4-d]pyrimidin-4-one | IC50 | 40 nM | US-20250114361: PYRAZOLOPYRIMIDINE COMPOUND AND PHARMACEUTICAL USE THEREOF |
| 1-(2-hydroxy-4-(trifluoromethyl)phenyl)-N- ((3R,5S)-5-methyl-1-(1H-tetrazol-5- yl)piperidin-3-yl)cyclopropane-1- carboxamide | IC50 | 41 nM | US-20260007684: AMIDE DERIVATIVES FOR INHIBITING NLRP3 AND USES THEREOF |
| (R)-1-(4-chloro-2-hydroxyphenyl)-N-(5,5- dimethyl-1-(1H-tetrazol-5-yl)piperidin-3- yl)cyclopropane-1-carboxamide | IC50 | 47 nM | US-20260007684: AMIDE DERIVATIVES FOR INHIBITING NLRP3 AND USES THEREOF |
| 2-(4-bromo-2,6-dimethylphenyl)-6-[1-(2-methoxyethyl)pyrazol-3-yl]-5H-pyrazolo[3,4-d]pyrimidin-4-one | IC50 | 47 nM | US-20250114361: PYRAZOLOPYRIMIDINE COMPOUND AND PHARMACEUTICAL USE THEREOF |
| 1-(4-chloro-2-hydroxyphenyl)-N-((3R,5S)- 5-methyl-1-(1H-tetrazol-5-yl)piperidin-3- yl)cyclopropane-1-carboxamide | IC50 | 48 nM | US-20260007684: AMIDE DERIVATIVES FOR INHIBITING NLRP3 AND USES THEREOF |
| 2-[4-(difluoromethoxy)-2,6-dimethylphenyl]-6-(1-methylpyrazol-3-yl)-5H-pyrazolo[3,4-d]pyrimidin-4-one | IC50 | 49 nM | US-20250114361: PYRAZOLOPYRIMIDINE COMPOUND AND PHARMACEUTICAL USE THEREOF |
| 2-(4-cyclopropyl-2,6-dimethylphenyl)-6-(1,4-dimethylpyrazol-3-yl)-5H-pyrazolo[3,4-d]pyrimidin-4-one | IC50 | 50 nM | US-20250114361: PYRAZOLOPYRIMIDINE COMPOUND AND PHARMACEUTICAL USE THEREOF |
| 2-(4-bromo-2,6-dimethylphenyl)-6-(2-methyl-1,3-oxazol-5-yl)-5H-pyrazolo[3,4-d]pyrimidin-4-one | IC50 | 53 nM | US-20250114361: PYRAZOLOPYRIMIDINE COMPOUND AND PHARMACEUTICAL USE THEREOF |
| 2-(4-cyclopropyl-2,6-dimethylphenyl)-6-[1-(difluoromethyl)pyrazol-3-yl]-5H-pyrazolo[3,4-d]pyrimidin-4-one | IC50 | 55 nM | US-20250114361: PYRAZOLOPYRIMIDINE COMPOUND AND PHARMACEUTICAL USE THEREOF |
| N-((1R,2R,6R)-9-(1H-tetrazol-5-yl)-9- azabicyclo[4.2.1]nonan-2-yl)-1-(4-chloro-2- hydroxyphenyl)cyclopropane-1- carboxamide | IC50 | 60 nM | US-20260007684: AMIDE DERIVATIVES FOR INHIBITING NLRP3 AND USES THEREOF |
| 2-(4-cyclopropyl-2,6-dimethylphenyl)-6-[1-(oxetan-3-yl)pyrazol-3-yl]-5H-pyrazolo[3,4-d]pyrimidin-4-one | IC50 | 62 nM | US-20250114361: PYRAZOLOPYRIMIDINE COMPOUND AND PHARMACEUTICAL USE THEREOF |
ChEMBL bioactivities
977 potent at pChembl≥5 of 1069 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).
| pChembl | Type | Value | Unit | Molecule |
|---|---|---|---|---|
| 10.15 | IC50 | 0.07 | nM | CHEMBL5419955 |
| 9.82 | IC50 | 0.15 | nM | CHEMBL5408007 |
| 9.52 | IC50 | 0.3 | nM | CHEMBL5429355 |
| 9.49 | IC50 | 0.32 | nM | NT-0796 |
| 9.42 | IC50 | 0.38 | nM | CHEMBL5435222 |
| 9.40 | IC50 | 0.4 | nM | CHEMBL5422139 |
| 9.40 | IC50 | 0.4 | nM | CHEMBL5426651 |
| 9.40 | IC50 | 0.4 | nM | CHEMBL5414596 |
| 9.30 | IC50 | 0.5 | nM | CHEMBL5408740 |
| 9.30 | IC50 | 0.5 | nM | CHEMBL5425624 |
| 9.30 | IC50 | 0.5 | nM | CHEMBL5438834 |
| 9.27 | Kd | 0.532 | nM | CHEMBL3183703 |
| 9.25 | IC50 | 0.56 | nM | CHEMBL5403928 |
| 9.24 | IC50 | 0.58 | nM | CHEMBL5423228 |
| 9.22 | IC50 | 0.6 | nM | CHEMBL5395560 |
| 9.22 | IC50 | 0.6 | nM | CHEMBL5395866 |
| 9.22 | IC50 | 0.6 | nM | CHEMBL5401306 |
| 9.21 | IC50 | 0.62 | nM | CHEMBL5427865 |
| 9.10 | IC50 | 0.8 | nM | CHEMBL5417431 |
| 9.10 | IC50 | 0.79 | nM | CHEMBL5422375 |
| 9.07 | IC50 | 0.843 | nM | CHEMBL5431540 |
| 9.00 | IC50 | 1 | nM | CHEMBL5411537 |
| 9.00 | IC50 | 1 | nM | CHEMBL5431981 |
| 9.00 | IC50 | 1 | nM | CHEMBL5433380 |
| 9.00 | IC50 | 1 | nM | CHEMBL5991941 |
| 9.00 | IC50 | 1 | nM | CHEMBL5992744 |
| 9.00 | IC50 | 1 | nM | CHEMBL5881090 |
| 8.96 | IC50 | 1.1 | nM | CHEMBL5427670 |
| 8.92 | IC50 | 1.2 | nM | CHEMBL5416002 |
| 8.89 | IC50 | 1.3 | nM | CHEMBL6177577 |
| 8.74 | IC50 | 1.8 | nM | CHEMBL5397239 |
| 8.74 | IC50 | 1.8 | nM | CHEMBL5400478 |
| 8.74 | IC50 | 1.8 | nM | CHEMBL6175164 |
| 8.72 | IC50 | 1.9 | nM | CHEMBL5430786 |
| 8.70 | IC50 | 2 | nM | CHEMBL5438164 |
| 8.70 | IC50 | 2 | nM | CHEMBL5801636 |
| 8.70 | IC50 | 2 | nM | CHEMBL6174073 |
| 8.68 | IC50 | 2.1 | nM | NT-0796 |
| 8.68 | IC50 | 2.1 | nM | CHEMBL6177729 |
| 8.64 | IC50 | 2.3 | nM | CHEMBL5592444 |
| 8.59 | IC50 | 2.6 | nM | CHEMBL6176278 |
| 8.54 | IC50 | 2.88 | nM | CHEMBL5597392 |
| 8.52 | IC50 | 3 | nM | CHEMBL5420448 |
| 8.52 | IC50 | 3 | nM | CHEMBL5405701 |
| 8.52 | IC50 | 3 | nM | CHEMBL5421060 |
| 8.52 | IC50 | 3 | nM | CHEMBL5423671 |
| 8.52 | IC50 | 3 | nM | CHEMBL5812129 |
| 8.52 | IC50 | 3 | nM | CHEMBL6188441 |
| 8.52 | IC50 | 3 | nM | CHEMBL6189801 |
| 8.51 | IC50 | 3.1 | nM | CHEMBL5424780 |
PubChem BioAssay actives
693 with measured affinity, of 1954 total; 50 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.
| Compound | Assay | Type | Value | Unit |
|---|---|---|---|---|
| propan-2-yl (2R)-3-(4-cyanopyrazol-1-yl)-2-(1,2,3,5,6,7-hexahydro-s-indacen-4-ylcarbamoyloxy)propanoate | 2020850: Inhibition of NLRP3 inflammasome activation in LPS-activated human PBMC cells assessed as inhibition of ATP/nigericin induced IL-1beta secretion preincubated with LPS for 3 hrs followed by compound addition for 30 mins and further stimulated with ATP for 1 hr by ELISA | ic50 | 0.0001 | uM |
| 5-[6-[(1-cyclobutylpiperidin-3-yl)amino]-4-methylpyridazin-3-yl]-1-benzothiophen-4-ol | 2037733: Inhibition of NLRP3 in human THP-1 cells assessed as reduction in IL-1beta production preincubated for 1 hrs followed by ATP addition measured after 18 hrs | ic50 | 0.0001 | uM |
| 2-(4-chloro-9-oxo-12-propan-2-yl-5-thia-1,10,11-triazatricyclo[6.4.0.02,6]dodeca-2(6),3,7,11-tetraen-10-yl)-N-[(3R)-1-cyclobutylpiperidin-3-yl]acetamide | 2037746: Inhibition of NLRP3 in LPS/nigericin induced PMA-differentiated human THP-1 cells assessed as reduction in IL-1beta production measured after 3 hrs | ic50 | 0.0003 | uM |
| propan-2-yl (2R)-2-(1,2,3,5,6,7-hexahydro-s-indacen-4-ylcarbamoyloxy)-3-pyrimidin-2-ylpropanoate | 2020850: Inhibition of NLRP3 inflammasome activation in LPS-activated human PBMC cells assessed as inhibition of ATP/nigericin induced IL-1beta secretion preincubated with LPS for 3 hrs followed by compound addition for 30 mins and further stimulated with ATP for 1 hr by ELISA | ic50 | 0.0003 | uM |
| 2-[4-methyl-6-[[(3R)-1-methylpiperidin-3-yl]amino]pyridazin-3-yl]-5-(trifluoromethyl)phenol | 2037724: Inhibition of NLRP3 in human THP-1 cells assessed as reduction in IL-1beta production measured after 3 hrs | ic50 | 0.0004 | uM |
| 2-[6-[[(3R)-1-methylpiperidin-3-yl]amino]-4-(trifluoromethyl)pyridazin-3-yl]-5-(trifluoromethyl)phenol | 2037724: Inhibition of NLRP3 in human THP-1 cells assessed as reduction in IL-1beta production measured after 3 hrs | ic50 | 0.0004 | uM |
| 5-cyclopropyl-2-[4-methyl-6-[[(3R)-1-methylpiperidin-3-yl]amino]pyridazin-3-yl]phenol | 2037751: Inhibition of NLRP3 in human PBMC cells assessed as reduction in TNFalpha level preincubated for 0.5 hrs followed by LPS treatment for 3.5 hrs and further addition of ATP measured after 45 mins | ic50 | 0.0004 | uM |
| 5-chloro-2-[2-[[(3R)-1-ethylpiperidin-3-yl]amino]-[1,3]oxazolo[4,5-b]pyridin-5-yl]-3-methylphenol | 2010083: Inhibition of NLRP3 in human THP-1 cells assessed as reduction in pyroptosis preincubated for 3 hrs followed by nigericin addition and measured after 1 hr by resazurin dye based microplate reader analysis | ic50 | 0.0004 | uM |
| 2-[2-[(3aR,7aS)-6-methyl-3,3a,4,5,7,7a-hexahydro-2H-pyrrolo[2,3-c]pyridin-1-yl]-[1,3]oxazolo[4,5-b]pyridin-5-yl]-5-chloro-3-methylphenol | 2010083: Inhibition of NLRP3 in human THP-1 cells assessed as reduction in pyroptosis preincubated for 3 hrs followed by nigericin addition and measured after 1 hr by resazurin dye based microplate reader analysis | ic50 | 0.0005 | uM |
| 2-[3-[1-(3-hydroxyphenyl)ethylamino]-5-methyl-1,2,4-triazin-6-yl]-5-(trifluoromethyl)phenol | 2037753: Inhibition of NLRP3 in human THP-1 cells assessed as reduction in IL-1beta production preincubated for 15 mins followed by ATP/LPS addition measured after 2 hrs by ELISA assay | ic50 | 0.0005 | uM |
| 5-chloro-2-[2-[[(3S)-1-ethylpiperidin-3-yl]amino]-[1,3]oxazolo[4,5-b]pyridin-5-yl]-3-methylphenol;2,2,2-trifluoroacetic acid | 2010083: Inhibition of NLRP3 in human THP-1 cells assessed as reduction in pyroptosis preincubated for 3 hrs followed by nigericin addition and measured after 1 hr by resazurin dye based microplate reader analysis | ic50 | 0.0005 | uM |
| 1-(1,2,3,5,6,7-hexahydro-s-indacen-4-yl)-3-[4-(2-hydroxypropan-2-yl)furan-2-yl]sulfonylurea | 2072297: Binding affinity to NLRP3 (unknown origin) expressed in HEK293T cells incubated for 30 mins by MST assay | kd | 0.0005 | uM |
| cyclopentyl (2R)-2-(1,2,3,5,6,7-hexahydro-s-indacen-4-ylcarbamoyloxy)-3-pyrimidin-2-ylpropanoate | 2020850: Inhibition of NLRP3 inflammasome activation in LPS-activated human PBMC cells assessed as inhibition of ATP/nigericin induced IL-1beta secretion preincubated with LPS for 3 hrs followed by compound addition for 30 mins and further stimulated with ATP for 1 hr by ELISA | ic50 | 0.0006 | uM |
| propan-2-yl (2R)-2-(1,2,3,5,6,7-hexahydro-s-indacen-4-ylcarbamoyloxy)-3-pyrazin-2-ylpropanoate | 2020850: Inhibition of NLRP3 inflammasome activation in LPS-activated human PBMC cells assessed as inhibition of ATP/nigericin induced IL-1beta secretion preincubated with LPS for 3 hrs followed by compound addition for 30 mins and further stimulated with ATP for 1 hr by ELISA | ic50 | 0.0006 | uM |
| propan-2-yl (2R)-2-(1,2,3,5,6,7-hexahydro-s-indacen-4-ylcarbamoyloxy)-3-(1,2,4-triazol-1-yl)propanoate | 2020850: Inhibition of NLRP3 inflammasome activation in LPS-activated human PBMC cells assessed as inhibition of ATP/nigericin induced IL-1beta secretion preincubated with LPS for 3 hrs followed by compound addition for 30 mins and further stimulated with ATP for 1 hr by ELISA | ic50 | 0.0006 | uM |
| 2-[2-[[(8S,8aR)-1,2,3,5,6,7,8,8a-octahydroindolizin-8-yl]amino]-[1,3]oxazolo[4,5-b]pyridin-5-yl]-5-chloro-3-methylphenol | 2010083: Inhibition of NLRP3 in human THP-1 cells assessed as reduction in pyroptosis preincubated for 3 hrs followed by nigericin addition and measured after 1 hr by resazurin dye based microplate reader analysis | ic50 | 0.0006 | uM |
| methyl 3-[(3S)-3-[[5-(4-chloro-2-hydroxy-6-methylphenyl)-[1,3]oxazolo[4,5-b]pyridin-2-yl]amino]piperidin-1-yl]propanoate | 2010083: Inhibition of NLRP3 in human THP-1 cells assessed as reduction in pyroptosis preincubated for 3 hrs followed by nigericin addition and measured after 1 hr by resazurin dye based microplate reader analysis | ic50 | 0.0006 | uM |
| 5-chloro-2-[2-[[(3S)-1-ethylpiperidin-3-yl]amino]-[1,3]oxazolo[4,5-b]pyridin-5-yl]-6-fluoro-3-methylphenol;2,2,2-trifluoroacetic acid | 2010083: Inhibition of NLRP3 in human THP-1 cells assessed as reduction in pyroptosis preincubated for 3 hrs followed by nigericin addition and measured after 1 hr by resazurin dye based microplate reader analysis | ic50 | 0.0006 | uM |
| 2-[6-[[(3S)-1-ethylpiperidin-3-yl]amino]pyridazin-3-yl]-3-methyl-5-(trifluoromethyl)phenol | 2037724: Inhibition of NLRP3 in human THP-1 cells assessed as reduction in IL-1beta production measured after 3 hrs | ic50 | 0.0008 | uM |
| 2-[4-[(3-hydroxy-3-methylcyclobutyl)amino]-5,7-dihydrofuro[3,4-d]pyridazin-1-yl]-5-(trifluoromethyl)phenol | 2037750: Inhibition of NLRP3 in human PBMC cells assessed as reduction in Il-1beta production preincubated for 0.5 hrs followed by LPS treatment for 3.5 hrs and further addition of ATP measured after 45 mins | ic50 | 0.0008 | uM |
| 2-[4-[[(3R)-1-methylpiperidin-3-yl]amino]-5,7-dihydrofuro[3,4-d]pyridazin-1-yl]-5-(trifluoromethyl)phenol | 2037750: Inhibition of NLRP3 in human PBMC cells assessed as reduction in Il-1beta production preincubated for 0.5 hrs followed by LPS treatment for 3.5 hrs and further addition of ATP measured after 45 mins | ic50 | 0.0008 | uM |
| ethyl 2-(1,2,3,5,6,7-hexahydro-s-indacen-4-ylcarbamoyloxy)-3-(1,2,4-triazol-1-yl)propanoate | 2020850: Inhibition of NLRP3 inflammasome activation in LPS-activated human PBMC cells assessed as inhibition of ATP/nigericin induced IL-1beta secretion preincubated with LPS for 3 hrs followed by compound addition for 30 mins and further stimulated with ATP for 1 hr by ELISA | ic50 | 0.0010 | uM |
| 2-[6-[[(3R)-1-ethylpiperidin-3-yl]amino]pyridazin-3-yl]-3-methyl-5-(trifluoromethyl)phenol | 2037757: Inhibition of NLRP3 in human THP-1 cells assessed as reduction in IL-1beta production preincubated for 1 hrs followed by nigericin addition measured after 3 hrs by HTRF assay | ic50 | 0.0010 | uM |
| 2-[5-methyl-3-[[(3R)-1-methylpiperidin-3-yl]amino]-1,2,4-triazin-6-yl]-5-(trifluoromethyl)phenol | 1956445: Inhibition of NLRP3 inflammasome activation in PMA-differentiated human THP-1 cells assessed as reduction in IL-1beta secretion preincubated for 20 hrs followed by nigericin addition and measured after 3 hrs by HTRF assay | ic50 | 0.0010 | uM |
| 5-chloro-2-[5-methyl-3-[[(3R)-1-methylpiperidin-3-yl]amino]-1,2,4-triazin-6-yl]phenol | 1956445: Inhibition of NLRP3 inflammasome activation in PMA-differentiated human THP-1 cells assessed as reduction in IL-1beta secretion preincubated for 20 hrs followed by nigericin addition and measured after 3 hrs by HTRF assay | ic50 | 0.0010 | uM |
| 5-cyclopropyl-2-[5-methyl-3-[[(3R)-1-methylpiperidin-3-yl]amino]-1,2,4-triazin-6-yl]phenol | 1956445: Inhibition of NLRP3 inflammasome activation in PMA-differentiated human THP-1 cells assessed as reduction in IL-1beta secretion preincubated for 20 hrs followed by nigericin addition and measured after 3 hrs by HTRF assay | ic50 | 0.0010 | uM |
| 3-fluoro-5-methyl-2-[5-methyl-3-[[(3R)-1-methylpiperidin-3-yl]amino]-1,2,4-triazin-6-yl]phenol | 1956445: Inhibition of NLRP3 inflammasome activation in PMA-differentiated human THP-1 cells assessed as reduction in IL-1beta secretion preincubated for 20 hrs followed by nigericin addition and measured after 3 hrs by HTRF assay | ic50 | 0.0010 | uM |
| 3-fluoro-5-methoxy-2-[5-methyl-3-[[(3R)-1-methylpiperidin-3-yl]amino]-1,2,4-triazin-6-yl]phenol | 1956445: Inhibition of NLRP3 inflammasome activation in PMA-differentiated human THP-1 cells assessed as reduction in IL-1beta secretion preincubated for 20 hrs followed by nigericin addition and measured after 3 hrs by HTRF assay | ic50 | 0.0010 | uM |
| 5-methoxy-2-[5-methyl-3-[[(3R)-1-methylpiperidin-3-yl]amino]-1,2,4-triazin-6-yl]phenol | 1956445: Inhibition of NLRP3 inflammasome activation in PMA-differentiated human THP-1 cells assessed as reduction in IL-1beta secretion preincubated for 20 hrs followed by nigericin addition and measured after 3 hrs by HTRF assay | ic50 | 0.0010 | uM |
| 5-methyl-2-[6-[[(3R)-1-methylpiperidin-3-yl]amino]-4,5-diazatricyclo[6.2.2.02,7]dodeca-2(7),3,5,9-tetraen-3-yl]phenol | 2037755: Inhibition of NLRP3 in human THP-1 cells assessed as reduction in IL-1beta production preincubated for 1 hrs followed by nigericin addition measured after 30 mins by ELISA assay | ic50 | 0.0010 | uM |
| 4-[6-[[(3R)-1-ethylpiperidin-3-yl]amino]pyridazin-3-yl]-3-hydroxy-5-methylbenzonitrile | 2011663: Inhibition of NLRP3 in human THP-1 cells assessed as reduction in pyroptosis preincubated with compound for 3 hrs followed by nigericin stimulation and measured after 1 hrs by resazurin dye based plate reader analysis | ic50 | 0.0011 | uM |
| 4-[6-[(3aR,7aS)-6-methyl-3,3a,4,5,7,7a-hexahydro-2H-pyrrolo[2,3-c]pyridin-1-yl]pyridazin-3-yl]-3-hydroxy-5-methylbenzonitrile | 2011663: Inhibition of NLRP3 in human THP-1 cells assessed as reduction in pyroptosis preincubated with compound for 3 hrs followed by nigericin stimulation and measured after 1 hrs by resazurin dye based plate reader analysis | ic50 | 0.0012 | uM |
| 3-hydroxy-4-[4-methyl-6-(6-methyl-3,3a,4,5,7,7a-hexahydro-2H-pyrrolo[2,3-c]pyridin-1-yl)pyridazin-3-yl]benzonitrile | 2011663: Inhibition of NLRP3 in human THP-1 cells assessed as reduction in pyroptosis preincubated with compound for 3 hrs followed by nigericin stimulation and measured after 1 hrs by resazurin dye based plate reader analysis | ic50 | 0.0018 | uM |
| 4-[6-[(3aR,7aS)-6-methyl-3,3a,4,5,7,7a-hexahydro-2H-pyrrolo[2,3-c]pyridin-1-yl]-4-methylpyridazin-3-yl]-3-hydroxybenzonitrile | 2011663: Inhibition of NLRP3 in human THP-1 cells assessed as reduction in pyroptosis preincubated with compound for 3 hrs followed by nigericin stimulation and measured after 1 hrs by resazurin dye based plate reader analysis | ic50 | 0.0018 | uM |
| 1-[amino-[(2S)-2-(hydroxymethyl)-2-methyl-3H-pyrazolo[5,1-b][1,3]oxazol-7-yl]-oxo-lambda6-sulfanylidene]-3-(1,2,3,5,6,7-hexahydro-s-indacen-4-yl)urea | 2037726: Inhibition of NLRP3 in human PBMC cells assessed as reduction in IL-1beta production measured after 3 hrs | ic50 | 0.0019 | uM |
| ethyl 3-(4-cyanopyrazol-1-yl)-2-(1,2,3,5,6,7-hexahydro-s-indacen-4-ylcarbamoyloxy)propanoate | 2020850: Inhibition of NLRP3 inflammasome activation in LPS-activated human PBMC cells assessed as inhibition of ATP/nigericin induced IL-1beta secretion preincubated with LPS for 3 hrs followed by compound addition for 30 mins and further stimulated with ATP for 1 hr by ELISA | ic50 | 0.0020 | uM |
| 5-[3-[[(3R)-1-(2-hydroxyethyl)piperidin-3-yl]amino]-5-methyl-1,2,4-triazin-6-yl]-2,3-dihydro-1-benzofuran-4-ol | 2117480: Inhibition of NLRP3 in LPS/nigericin induced human THP-1 cells assessed as reduction in pyroptosis pretreated for 3 hrs in presence of LPS followed by nigericin addition and measured after 1 hr by resazurin dye based analysis | ic50 | 0.0023 | uM |
| 5-[6-[[(3R)-1-(2-hydroxyethyl)piperidin-3-yl]amino]-4,5-diazatricyclo[6.2.2.02,7]dodeca-2(7),3,5-trien-3-yl]-1-benzofuran-4-ol | 2122638: Inhibition of NLRP3 inflammasome activation in LPS/nigericin stimulated human PBMC assessed as reduction in IL-1beta release pretreated with LPS for 3 hrs followed by compound addition for 40 mins prior to nigericin stimulation for 40 mins by ELISA | ic50 | 0.0029 | uM |
| 2-[(2’S,4R)-2’-fluoro-6-iodo-1-oxospiro[3H-isoquinoline-4,1’-cyclopropane]-2-yl]-N-(3-hydroxy-3-methylcyclobutyl)acetamide | 2037720: Inhibition of NLRP3 in human THP-1 cells assessed as reduction in IL-1beta production | ic50 | 0.0030 | uM |
| 2-(4-bromo-2,6-dimethylphenyl)-6-(2-methylpropylamino)-5H-pyrazolo[3,4-d]pyrimidin-4-one | 2037720: Inhibition of NLRP3 in human THP-1 cells assessed as reduction in IL-1beta production | ic50 | 0.0030 | uM |
| 2-(4-bromo-2,6-dimethylphenyl)-6-(2,3-dihydro-1,4-oxazin-4-yl)-5H-pyrazolo[3,4-d]pyrimidin-4-one | 2037720: Inhibition of NLRP3 in human THP-1 cells assessed as reduction in IL-1beta production | ic50 | 0.0030 | uM |
| 3-hydroxy-4-[4-[(3-hydroxy-3-methylcyclobutyl)amino]-5,6,7,8-tetrahydrophthalazin-1-yl]benzonitrile | 2037755: Inhibition of NLRP3 in human THP-1 cells assessed as reduction in IL-1beta production preincubated for 1 hrs followed by nigericin addition measured after 30 mins by ELISA assay | ic50 | 0.0030 | uM |
| 4-[6-[[(3R)-1-ethylpiperidin-3-yl]amino]-4-methylpyridazin-3-yl]-3-hydroxybenzonitrile;formic acid | 2011663: Inhibition of NLRP3 in human THP-1 cells assessed as reduction in pyroptosis preincubated with compound for 3 hrs followed by nigericin stimulation and measured after 1 hrs by resazurin dye based plate reader analysis | ic50 | 0.0031 | uM |
| 1-[(E)-3-(dimethylamino)prop-1-enyl]sulfonyl-3-(1,2,3,5,6,7-hexahydro-s-indacen-4-yl)urea | 2037716: Inhibition of NLRP3 in human THP-1 cells assessed as reduction in IL-1beta production measured after 1 hrs in presence of ATP | ic50 | 0.0032 | uM |
| (2S)-2-[(4-aminophenyl)sulfonylamino]-N-(1,2,3,5,6,7-hexahydro-s-indacen-4-yl)-3-(4-hydroxyphenyl)propanamide | 2029913: Inhibition of NLRP3 inflammasome activation in LPS-treated human THP-1 cells assessed as inhibition of ATP-stimulated IL-1beta release at 1 uM incubated for 30 mins followed by ATP stimulation for 1 hr by ELISA method | ic50 | 0.0033 | uM |
| 4-[8-[(3R)-1-ethylpiperidin-3-yl]-6,7-dihydropyridazino[4,3-b][1,4]oxazin-3-yl]-3-hydroxy-5-methylbenzonitrile;formic acid | 2126500: Inhibition of NLRP3 dependent pyroptosis in human THP-1 cells preincubated with compound for 3 hrs followed by nigericin addition and measured after 1 hrs by resazurin dye based assay | ic50 | 0.0034 | uM |
| 1-[(E)-3-(dimethylamino)prop-1-enyl]sulfonyl-3-(1,2,3,5-tetrahydro-s-indacen-4-yl)urea | 2037716: Inhibition of NLRP3 in human THP-1 cells assessed as reduction in IL-1beta production measured after 1 hrs in presence of ATP | ic50 | 0.0036 | uM |
| 4-[(3R)-3-[[6-(4-hydroxy-2,3-dihydro-1-benzofuran-5-yl)-5-methyl-1,2,4-triazin-3-yl]amino]piperidin-1-yl]butanoic acid | 2117480: Inhibition of NLRP3 in LPS/nigericin induced human THP-1 cells assessed as reduction in pyroptosis pretreated for 3 hrs in presence of LPS followed by nigericin addition and measured after 1 hr by resazurin dye based analysis | ic50 | 0.0042 | uM |
| 2-[4-methyl-6-[[(3R)-1-methylpiperidin-3-yl]amino]pyridazin-3-yl]naphthalen-1-ol | 2037733: Inhibition of NLRP3 in human THP-1 cells assessed as reduction in IL-1beta production preincubated for 1 hrs followed by ATP addition measured after 18 hrs | ic50 | 0.0043 | uM |
| 1-[amino-[4-fluoro-1-[(2S)-2-hydroxypropyl]pyrazol-3-yl]-oxo-lambda6-sulfanylidene]-3-spiro[2-azatricyclo[7.3.0.03,7]dodeca-1(9),2,7-triene-4,1’-cyclopropane]-8-ylurea | 2037720: Inhibition of NLRP3 in human THP-1 cells assessed as reduction in IL-1beta production | ic50 | 0.0047 | uM |
CTD chemical–gene interactions
193 total (human), top 30 by PubMed support.
| Chemical | Actions (top 5) | PubMed papers |
|---|---|---|
| Lipopolysaccharides | decreases reaction, increases expression, affects cotreatment, increases reaction, increases activity (+4 more) | 21 |
| Acetylcysteine | affects cotreatment, increases abundance, increases reaction, decreases ubiquitination, affects reaction (+2 more) | 19 |
| Adenosine Triphosphate | decreases reaction, increases expression, increases activity, affects reaction, affects cotreatment | 12 |
| N-(1,2,3,5,6,7-hexahydro-S-indacen-4-ylcarbamoyl)-4-(2-hydroxy-2-propanyl)-2-furansulfonamide | affects cotreatment, increases expression, decreases reaction, increases reaction, decreases activity (+2 more) | 11 |
| Cadmium Chloride | decreases reaction, affects reaction, increases cleavage, increases abundance, increases expression (+3 more) | 10 |
| Particulate Matter | increases abundance, increases expression, decreases expression, affects reaction, affects expression (+1 more) | 9 |
| lipopolysaccharide, Escherichia coli O111 B4 | affects cotreatment, increases expression, affects expression, affects reaction, decreases reaction (+1 more) | 7 |
| Cadmium | decreases reaction, increases abundance, increases expression, affects reaction, increases secretion | 6 |
| Glucose | affects cotreatment, affects reaction, increases reaction, decreases reaction, increases expression | 6 |
| sodium arsenite | decreases expression, decreases reaction, increases abundance, increases expression, increases reaction | 5 |
| Silicon Dioxide | decreases reaction, increases expression, affects localization, affects cotreatment, increases activity | 5 |
| 3-methyladenine | decreases reaction, increases expression, affects cotreatment, increases reaction | 4 |
| Air Pollutants | decreases expression, increases abundance, increases expression, decreases reaction | 4 |
| Nickel | increases abundance, increases expression, decreases reaction | 4 |
| Asbestos, Crocidolite | increases secretion, increases reaction, increases expression, decreases reaction, affects reaction (+1 more) | 4 |
| 3-(4-methylphenylsulfonyl)-2-propenenitrile | decreases activity, decreases reaction, increases abundance, increases expression | 3 |
| Resveratrol | increases abundance, affects cotreatment, increases expression, decreases reaction | 3 |
| Acrolein | affects cotreatment, increases expression, increases reaction, decreases reaction, affects reaction (+1 more) | 3 |
| Ethanol | affects cotreatment, decreases reaction, increases expression | 3 |
| Arsenic | affects methylation, decreases expression, decreases reaction, increases abundance, increases expression | 3 |
| Quercetin | increases secretion, decreases reaction, increases abundance, increases expression, increases reaction | 3 |
| Uric Acid | affects reaction, increases cleavage, increases secretion, decreases reaction, increases expression (+2 more) | 3 |
| tetrachlorobenzoquinone | decreases ubiquitination, increases expression, affects reaction, increases reaction, increases secretion (+2 more) | 2 |
| ML385 | affects cotreatment, decreases reaction, increases expression | 2 |
| ruscogenin | decreases reaction, increases expression | 2 |
| pyrrolidine dithiocarbamic acid | increases reaction, decreases reaction, increases expression | 2 |
| puerarin | decreases reaction, increases expression, increases reaction | 2 |
| 4-phenylbutyric acid | decreases reaction, increases expression | 2 |
| SB 203580 | increases expression, increases abundance, decreases reaction | 2 |
| pyrazolanthrone | decreases reaction, increases expression, increases abundance | 2 |
ChEMBL screening assays
534 unique, capped per target: 527 binding, 6 functional, 1 admet
Representative assays (with source publication via chembl_document):
| Assay ID | Type | Description | Source paper |
|---|---|---|---|
| CHEMBL1737963 | Functional | PUBCHEM_BIOASSAY: Dose Response confirmation of uHTS for the identification of inhibitors of NALP3 in yeast using a luminescent assay. (Class of assay: confirmatory) [Related pubchem assays (depositor defined):AID2825, AID2832] | PubChem BioAssay data set |
| CHEMBL3390772 | Binding | Inhibition of recombinant NLRP3-ATPase (unknown origin) assessed as hydrolysis of ATP at 10 uM | Electrophilic warhead-based design of compounds preventing NLRP3 inflammasome-dependent pyroptosis. — J Med Chem |
| CHEMBL4026427 | ADMET | Agonist activity at NLRP3 in human THLP1-null cells assessed as induction of LPS-induced IL-1beta secretion by HEK-Blue reporter cell based assay | Nonpyrogenic Molecular Adjuvants Based on norAbu-Muramyldipeptide and norAbu-Glucosaminyl Muramyldipeptide: Synthesis, Molecular Mechanisms of Action, and Biological Activities in Vitro and in Vivo. — J Med Chem |
Cellosaurus cell lines
6 cell lines: 4 cancer cell line, 2 induced pluripotent stem cell
First 10 cell lines (id-ordered, not curated):
| Cellosaurus | Name | Category | Sex |
|---|---|---|---|
| CVCL_A8AS | THP1-KO-NLRP3 | Cancer cell line | Male |
| CVCL_B9Z7 | Abcam THP-1 NLRP3 KO | Cancer cell line | Male |
| CVCL_E1D5 | Ubigene THP-1 NLRP3 KO | Cancer cell line | Male |
| CVCL_T776 | CiRA086Ai-m1 | Induced pluripotent stem cell | Male |
| CVCL_T777 | CiRA188Ai-M1 | Induced pluripotent stem cell | Male |
| CVCL_X600 | THP1-defNLRP3 | Cancer cell line | Male |
Clinical trials (associated diseases)
275 trials via MONDO — disease-level, not drug-specific.
| Trial | Phase | Status | Title |
|---|---|---|---|
| NCT02422056 | PHASE4 | COMPLETED | Acid Tranexamic Effectiveness in Reducing the Intraoperative Bleeding in Palatoplasty |
| NCT02915042 | PHASE4 | WITHDRAWN | Dexmedetomidine vs Placebo for Pediatric Cleft Palate Repair |
| NCT02953145 | PHASE4 | WITHDRAWN | The Use of Fibrin Sealant to Reduce Post Operative Pain in Cleft Palate Surgery |
| NCT03632044 | PHASE4 | ACTIVE_NOT_RECRUITING | Evaluation of Trigeminal Nerve Blockade |
| NCT06962306 | PHASE4 | RECRUITING | Optimizing Perioperative Analgesia to Lower Pain Following Cleft Palate Surgery |
| NCT02399566 | PHASE4 | UNKNOWN | Clinical Trial of Erlotinib and Pemetrexed for Maintenance Treatment in Lung Adenocarcinoma |
| NCT02804646 | PHASE4 | UNKNOWN | Endostar Durative Transfusion Combined With Chemotherapy in the Treatment of Advanced Lung Adenocarcinoma |
| NCT00685373 | PHASE3 | COMPLETED | Efficacy and Safety of ACZ885 in Patients With the Following Cryopyrin-associated Periodic Syndromes: Familial Cold Autoinflammatory Syndrome, Muckle-Wells Syndrome, or Neonatal Onset Multisystem Inflammatory Disease |
| NCT00770601 | PHASE3 | TERMINATED | Canakinumab to Treat Neonatal-Onset Multisystem Inflammatory Disease |
| NCT00991146 | PHASE3 | COMPLETED | Efficacy and Safety Study of Canakinumab Administered for 6 Months (24 Weeks) in Japanese Patients With Cryopyrin-associated Periodic Syndromes Followed by an Extension Phase |
| NCT01302860 | PHASE3 | COMPLETED | Efficacy, Safety and Tolerability of ACZ885 in Pediatric Patients With the Following Cryopyrin-associated Periodic Syndromes: Familial Cold Autoinflammatory Syndrome, Muckle-Wells Syndrome, or Neonatal Onset Multisystem Inflammatory Disease |
| NCT01576367 | PHASE3 | COMPLETED | Efficacy, Safety and Tolerability of ACZ885 in Pediatric Patients With the Following Cryopyrin-associated Periodic Syndromes: Familial Cold Autoinflammatory Syndrome, Muckle-Wells Syndrome, or Neonatal Onset Multisystem Inflammatory Disease |
| NCT01105507 | PHASE3 | COMPLETED | The Safety and Efficacy of Canakinumab in Patients Aged 4 Years or Older Diagnosed With Cryopyrin-associated Periodic Syndromes (CAPS) in Canada |
| NCT00288704 | PHASE3 | COMPLETED | Rilonacept for Treatment of Cryopyrin-Associated Periodic Syndromes (CAPS) |
| NCT00465985 | PHASE3 | COMPLETED | Efficacy, Safety, and Tolerability of ACZ885 in Patients With Muckle-Wells Syndrome |
| NCT00098319 | PHASE3 | COMPLETED | Oral Cleft Prevention Trial in Brazil |
| NCT00397917 | PHASE3 | COMPLETED | Oral Cleft Prevention Program |
| NCT04928352 | PHASE3 | RECRUITING | Nebulized Bupivacaine Analgesia for Cleft Palate Repair |
| NCT04928391 | PHASE3 | COMPLETED | A Single Bolus of Dexmedetomidine Versus Normal Saline in Postoperative Agitation |
| NCT00002852 | PHASE3 | COMPLETED | Surgery With or Without Chemotherapy in Treating Patients With Stage I Non-small Cell Lung Cancer |
| NCT00005838 | PHASE3 | COMPLETED | Combination Chemotherapy Plus Radiation Therapy With or Without AE-941 in Treating Patients With Stage III Non-small Cell Lung Cancer That Cannot Be Removed By Surgery |
| NCT00020709 | PHASE3 | COMPLETED | Combination Chemotherapy and Radiation Therapy With or Without Gefitinib in Treating Patients With Stage III Non-Small Cell Lung Cancer That Cannot Be Removed By Surgery |
| NCT00049543 | PHASE3 | COMPLETED | Gefitinib in Treating Patients With Stage IB, II, or IIIA Non-small Cell Lung Cancer That Was Completely Removed by Surgery |
| NCT00946712 | PHASE3 | TERMINATED | S0819: Carboplatin and Paclitaxel With or Without Bevacizumab and/or Cetuximab in Treating Patients With Stage IV or Recurrent Non-Small Cell Lung Cancer |
| NCT01798485 | PHASE3 | TERMINATED | A Phase 3 Study of Ganetespib in Combination With Docetaxel Versus Docetaxel Alone in Patients With Advanced NSCLC |
| NCT02011997 | PHASE3 | UNKNOWN | Comparison of cVATS Segmentectomy Versus Lobectomy for Lung Adenocarcinoma in Situ and With Microinvasion |
| NCT03391869 | PHASE3 | ACTIVE_NOT_RECRUITING | Nivolumab and Ipilimumab With or Without Local Consolidation Therapy in Treating Patients With Stage IV Non-Small Cell Lung Cancer |
| NCT03676192 | PHASE3 | COMPLETED | To Compare Efficacy and Safety of CT-P16 and European Union-Approved Avastin as First-Line Treatment for Metastatic or Recurrent Non-Squamous Non-Small Cell Lung Cancer |
| NCT04339218 | PHASE3 | RECRUITING | Cryoablation in Combination (or Not) With Pembrolizumab and Pemetrexed-carboplatin in 1st-line Treatment for Patients With Metastatic Lung Adenocarcinoma |
| NCT05204758 | PHASE3 | COMPLETED | Prophylactic TCM for Mitigation of EGFR-TKI Related Dermatological Adverse Effect |
| NCT05717803 | PHASE3 | RECRUITING | Segmentectomy for Ground Glass-dominant Invasive Lung Cancer (ECTOP-1012) |
| NCT05943795 | PHASE3 | ACTIVE_NOT_RECRUITING | A Clinical Study of SI-B001 Combined With Docetaxel in the Treatment of Non-small Cell Lung Adenocarcinoma and Lung Squamous Cell Carcinoma |
| NCT06031181 | PHASE3 | RECRUITING | Sublobar Resection for Adenocarcinoma in Situ/Minimally Invasive Adenocarcinoma Diagnosed by Intraoperative Frozen Section (ECTOP-1019) |
| NCT06031246 | PHASE3 | RECRUITING | Selective Lymph Node Dissection for cT1N0M0 Invasive NSCLC With CTR>0.5 Located in the Apical Segment (ECTOP-1018) |
| NCT06634966 | PHASE3 | RECRUITING | Segmentectomy for Solid-dominant Lung Cancer |
| NCT07169903 | PHASE3 | NOT_YET_RECRUITING | Segmentectomy vs Lobectomy for 2 - 3cm IASLC Grade 1-2 Lung Adenocarcinoma: A Multi-center RCT |
| NCT07481786 | PHASE3 | RECRUITING | Bevacizumab Plus FSRT Versus Hippocampus-Avoidant WBRT in Lung Adenocarcinoma With Extensive Brain Metastases |
| NCT03923140 | PHASE2 | UNKNOWN | A Clinical Study of Tranilast in the Treatment of Cryopyrin-Associated Periodic Syndrome (CAPS) |
| NCT04524858 | PHASE2 | TERMINATED | Study of ATI-450 in Patients With Cryopyrin-Associated Periodic Syndrome (CAPS) |
| NCT05186051 | PHASE2 | COMPLETED | A Clinical Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of ZYIL1 in Subjects With Cryopyrin Associated Periodic Syndromes (CAPS) |
Related Atlas pages
- Associated diseases: keratitis fugax hereditaria, CINCA syndrome, cryopyrin-associated periodic syndrome, familial cold autoinflammatory syndrome, Muckle-Wells syndrome, familial cold autoinflammatory syndrome 1
- Targeted by drugs: Nibrozetone
- Disease cohort memberships (association, not causation — diseases whose associated-gene cohort lists this gene; a subset are also under Associated diseases): arteriovenous malformations of the brain, atypical hemolytic-uremic syndrome, autoinflammatory syndrome, CINCA syndrome, cleft palate, cryopyrin-associated periodic syndrome, familial cold autoinflammatory syndrome, familial cold autoinflammatory syndrome 1, focal segmental glomerulosclerosis, hearing loss disorder, hearing loss, autosomal dominant 34, with or without inflammation, keratitis fugax hereditaria, kidney disorder, long COVID-19, lung adenocarcinoma, Muckle-Wells syndrome, pericardial effusion, squamous cell carcinoma