RIPK1
gene geneOn this page
Also known as RIPRIP1RIP-1
Summary
RIPK1 (receptor interacting serine/threonine kinase 1, HGNC:10019) is a protein-coding gene on chromosome 6p25.2, encoding Receptor-interacting serine/threonine-protein kinase 1 (Q13546). Serine-threonine kinase which is a key regulator of TNF-mediated apoptosis, necroptosis and inflammatory pathways.
This gene encodes a member of the receptor-interacting protein (RIP) family of serine/threonine protein kinases. The encoded protein plays a role in inflammation and cell death in response to tissue damage, pathogen recognition, and as part of developmental regulation. RIPK1/RIPK3 kinase-mediated necrosis is referred to as necroptosis. Genetic disruption of this gene in mice results in death shortly after birth.
Source: NCBI Gene 8737 — RefSeq curated summary.
At a glance
- Gene–disease (curated): immunodeficiency 57 (Definitive, ClinGen) — +2 more curated relationships
- GWAS associations: 2
- Clinical variants (ClinVar): 588 total — 22 pathogenic, 7 likely-pathogenic
- Phenotypes (HPO): 28
- Druggable target: yes — 24 molecules with ChEMBL bioactivity
- Cancer driver (intOGen): loss-of-function (tumor-suppressor-like) across 1 cancer types
- MANE Select transcript:
NM_001354930
Identifiers
Gene identifiers
| Field | Value |
|---|---|
| HGNC ID | HGNC:10019 |
| Approved symbol | RIPK1 |
| Name | receptor interacting serine/threonine kinase 1 |
| Location | 6p25.2 |
| Locus type | gene with protein product |
| Status | Approved |
| Aliases | RIP, RIP1, RIP-1 |
| Ensembl gene | ENSG00000137275 |
| Ensembl biotype | protein_coding |
| OMIM | 603453 |
| Entrez | 8737 |
Gene structure
Transcript identifiers
Ensembl transcripts: 36 — 19 protein_coding, 8 nonsense_mediated_decay, 5 protein_coding_CDS_not_defined, 4 retained_intron
ENST00000259808, ENST00000380409, ENST00000479389, ENST00000676591, ENST00000676618, ENST00000676758, ENST00000676965, ENST00000676995, ENST00000677261, ENST00000677361, ENST00000677799, ENST00000678084, ENST00000678809, ENST00000678874, ENST00000679118, ENST00000679335, ENST00000679677, ENST00000679775, ENST00000680389, ENST00000858490, ENST00000858491, ENST00000858492, ENST00000858493, ENST00000858494, ENST00000858495, ENST00000919965, ENST00000919966, ENST00000967576, ENST00000967577, ENST00000967578, ENST00000967579, ENST00000967580, ENST00000967581, ENST00000967582, ENST00000967583, ENST00000967584
RefSeq mRNA: 7 — MANE Select: NM_001354930
NM_001317061, NM_001354930, NM_001354931, NM_001354932, NM_001354933, NM_001354934, NM_003804
CCDS: CCDS4482, CCDS93851
Canonical transcript exons
ENST00000259808 — 11 exons
| Exon | Start | End |
|---|---|---|
| ENSE00000928603 | 3110803 | 3110955 |
| ENSE00000928611 | 3076764 | 3076987 |
| ENSE00001484818 | 3068494 | 3068661 |
| ENSE00001529807 | 3113053 | 3115187 |
| ENSE00003533855 | 3105482 | 3106051 |
| ENSE00003554977 | 3077779 | 3077935 |
| ENSE00003575873 | 3080979 | 3081116 |
| ENSE00003586162 | 3083085 | 3083313 |
| ENSE00003618773 | 3104225 | 3104315 |
| ENSE00003637819 | 3085259 | 3085408 |
| ENSE00003647211 | 3089581 | 3089657 |
Expression profiles
Bgee: expression breadth ubiquitous, 238 present calls, max score 91.05.
FANTOM5 (CAGE): breadth ubiquitous, TPM avg 23.8449 / max 1044.9606, expressed in 1820 samples.
FANTOM5 promoters (5 alternative TSS)
| Promoter ID | TPM avg | Samples expressed |
|---|---|---|
| 65518 | 17.3145 | 1817 |
| 65515 | 5.3552 | 1048 |
| 65516 | 0.7808 | 146 |
| 65519 | 0.2557 | 107 |
| 65517 | 0.1387 | 69 |
Top tissues by expression
277 total, by Bgee expression score (0-100, higher = more expressed):
| Tissue | Anatomy ID | Expression score | Quality |
|---|---|---|---|
| granulocyte | CL:0000094 | 91.05 | gold quality |
| sural nerve | UBERON:0015488 | 90.39 | gold quality |
| right lobe of liver | UBERON:0001114 | 88.92 | gold quality |
| stromal cell of endometrium | CL:0002255 | 88.60 | gold quality |
| mucosa of stomach | UBERON:0001199 | 88.48 | gold quality |
| calcaneal tendon | UBERON:0003701 | 88.37 | gold quality |
| small intestine Peyer’s patch | UBERON:0003454 | 88.07 | gold quality |
| right coronary artery | UBERON:0001625 | 88.02 | gold quality |
| skin of abdomen | UBERON:0001416 | 87.97 | gold quality |
| omental fat pad | UBERON:0010414 | 87.88 | gold quality |
| peritoneum | UBERON:0002358 | 87.85 | gold quality |
| skin of leg | UBERON:0001511 | 87.75 | gold quality |
| lower esophagus muscularis layer | UBERON:0035833 | 87.70 | gold quality |
| lower esophagus | UBERON:0013473 | 87.69 | gold quality |
| apex of heart | UBERON:0002098 | 87.67 | gold quality |
| descending thoracic aorta | UBERON:0002345 | 87.64 | gold quality |
| transverse colon | UBERON:0001157 | 87.45 | gold quality |
| rectum | UBERON:0001052 | 87.39 | gold quality |
| tibial artery | UBERON:0007610 | 87.38 | gold quality |
| popliteal artery | UBERON:0002250 | 87.36 | gold quality |
| mucosa of transverse colon | UBERON:0004991 | 87.35 | gold quality |
| esophagogastric junction muscularis propria | UBERON:0035841 | 87.31 | gold quality |
| subcutaneous adipose tissue | UBERON:0002190 | 87.24 | gold quality |
| muscle layer of sigmoid colon | UBERON:0035805 | 87.21 | gold quality |
| esophagus | UBERON:0001043 | 87.08 | gold quality |
| adipose tissue of abdominal region | UBERON:0007808 | 87.08 | gold quality |
| body of stomach | UBERON:0001161 | 87.03 | gold quality |
| aorta | UBERON:0000947 | 87.00 | gold quality |
| gall bladder | UBERON:0002110 | 86.82 | gold quality |
| small intestine | UBERON:0002108 | 86.73 | gold quality |
Single-cell (SCXA)
Detected in 2 experiment(s), a significant marker in 1.
| Experiment | Marker? | Max mean expression |
|---|---|---|
| E-CURD-10 | no | 146.63 |
| E-ANND-3 | no | 0.00 |
Regulation
Is transcription factor: no
Upstream regulators (CollecTRI, top): AP1, NFKB1, PDX1, REL, SP1, STAT1, ZGLP1
miRNA regulators (miRDB)
49 targeting RIPK1, 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-4682 | 100.00 | 68.89 | 1258 |
| HSA-MIR-432-3P | 100.00 | 67.86 | 705 |
| HSA-MIR-3185 | 99.99 | 68.12 | 1959 |
| HSA-MIR-12136 | 99.98 | 72.81 | 5713 |
| HSA-MIR-3065-5P | 99.97 | 71.56 | 3281 |
| HSA-MIR-153-5P | 99.89 | 73.86 | 6317 |
| HSA-MIR-4492 | 99.87 | 68.25 | 3611 |
| HSA-MIR-548AZ-5P | 99.83 | 69.94 | 3230 |
| HSA-MIR-548T-5P | 99.83 | 69.91 | 3220 |
| HSA-MIR-5004-5P | 99.68 | 66.63 | 1294 |
| HSA-MIR-3175 | 99.65 | 66.30 | 2031 |
| HSA-MIR-3679-3P | 99.64 | 69.88 | 1599 |
| HSA-MIR-4261 | 99.59 | 70.30 | 3415 |
| HSA-MIR-7159-5P | 99.53 | 72.12 | 2472 |
| HSA-MIR-642A-5P | 99.51 | 65.10 | 1152 |
| HSA-MIR-6740-3P | 99.48 | 68.49 | 1392 |
| HSA-MIR-766-3P | 99.47 | 65.24 | 1811 |
| HSA-MIR-147B-5P | 99.45 | 70.62 | 2432 |
| HSA-MIR-4797-5P | 99.39 | 68.01 | 1354 |
| HSA-MIR-4505 | 99.27 | 67.81 | 2678 |
| HSA-MIR-5693 | 99.24 | 66.67 | 1106 |
| HSA-MIR-664A-3P | 99.22 | 71.08 | 2696 |
| HSA-MIR-5787 | 99.22 | 67.86 | 2628 |
| HSA-MIR-21-3P | 99.21 | 68.95 | 1312 |
| HSA-MIR-122B-3P | 99.21 | 68.90 | 1333 |
| HSA-MIR-661 | 99.09 | 65.94 | 2062 |
| HSA-MIR-4656 | 98.79 | 66.22 | 1306 |
| HSA-MIR-5006-5P | 98.79 | 66.92 | 1246 |
| HSA-MIR-502-5P | 98.77 | 66.51 | 906 |
| HSA-MIR-4700-5P | 98.63 | 67.43 | 1915 |
Literature-anchored findings (GeneRIF, showing 40)
- cells pre-stimulated through TNFR-2 prior to subsequent activation of TNFR-1, showed enhanced cell death and recruitment of RIP to the TNFR-1 complex; deficiency of RIP rescued the infected cells from TNF-induced cytotoxicity (PMID:14532286)
- FAK overexpression in human tumors provides a survival signal function by binding to RIP and inhibiting its interaction with the death receptor complex. (PMID:15121855)
- RIP-dependent recruitment of MEKK3 plays a specific role in TNF-alpha signaling. (PMID:15572679)
- TAK1 is recruited to the TNF-R1 complex via RIP and likely cooperates with MEKK3 to activate NF-kappaB in TNF-alpha signaling (PMID:16260783)
- This study provides the first genetic evidence that the ubiquitination of RIP is required for TNFalpha-induced NF-kappaB activation. (PMID:16543241)
- Activation of IKK by TNF-alpha requires site-specific ubiquitination of RIP1. (PMID:16603398)
- TRADD and RIP1 compete for recruitment to the TNFR1 signaling complex and the distinct programs of cell death. (PMID:16611992)
- RIP is one of the critical components involved in mediating DNA damage-induced, p53-independent cell death (PMID:16825191)
- The expression of receptor-interacting protein 1 (RIP1) in peripheral blood mononuclear cells was significantly decreased in SLE patients. (PMID:17235653)
- RIP may serve as a general activator of IRF7, responding to and transmitting the signals from various stimuli, and that ubiquitination may be a general mechanism for enhancing the activity of IRF7. (PMID:17296724)
- We describe how RIP1 acts as a key integrator of signalling pathways initiated by stimulation of death receptors, bacterial or viral infection, genotoxic stress and T-cell homeostasis. (PMID:17301840)
- findings show ubiquitination of RIP1 inhibits TNF-induced apoptosis first through an NF-kappaB-independent mechanism, then through an NF-kappaB-dependent mechanism; in absence of ubiquitination, RIP1 serves as a proapoptotic signaling molecule (PMID:17306544)
- TNF-induced TRAF2-RIP1-AIP1-ASK1 complex formation and for the activation of ASK1-JNK/p38 apoptotic signaling. (PMID:17389591)
- TNFRSF is upregulated after radical prostatectomy for prostatic neoplasms. (PMID:17448597)
- RIP and c-FLIP-mediated assembly of the death-inducing signaling complex in nonrafts is a critical upstream event in TRAIL resistance (PMID:17638906)
- These results suggested that HPB-ALL cells have a caspase-independent RIP kinasedependent pathway for Fas ligation. (PMID:17951993)
- In response to autocrine TNFalpha signaling, the Smac mimetic promotes formation of a RIPK1-dependent caspase-8-activating complex, leading to apoptosis (PMID:17996648)
- Data demonstrated that CK1alpha interacted with and phosphorylated RIP1 at the intermediate domain. Finally, we showed that CK1alpha enhanced RIP1-mediated NF-kappaB activation. (PMID:18067272)
- Cezanne forms a novel negative feedback loop in pro-inflammatory signaling and that it suppresses NF-kappaB activation by targeting RIP1 signaling intermediaries for deubiquitination (PMID:18178551)
- cytomegalovirus M45 protein provides a direct cell type-dependent replication benefit to the virus while modulating other biological processes signaling via the RIP1 adaptor such as activation of Toll-like receptor (TLR)3 and other mediators of cell death (PMID:18442983)
- activation and formation of TICAM-1 signalosomes with NF-kappaB and interferon regulatory factor-3 requires oligomerization induced at two different sites and RIP1 binding (PMID:18450748)
- cIAP1 and cIAP2 promote cancer cell survival by functioning as E3 ubiquitin ligases that maintain constitutive ubiquitination of the RIP1 adaptor protein. (PMID:18570872)
- c-IAP1 and c-IAP2 are required for TNFalpha-stimulated RIP1 ubiquitination and NF-kappaB activation. (PMID:18621737)
- The protein encoded by the hybrid transcript lacks the putative kinase domain of RIP1, but potently stimulates NFkappaB, AP-1 and Ets-1 activity. (PMID:18635966)
- the simultaneous downregulation of uPAR and MMP-9 induces apoptosome-mediated apoptosis through FADD-associated protein RIP and caspase 9 (PMID:18813792)
- Induction of NF-kappa B depends upon the adaptor receptor-interacting protein kinase (RIP)1, acting via a RIP homotypic interaction motif-dependent interaction with DNA-dependent activator of IFN regulatory factors (DAI). (PMID:18941233)
- glomerular and tubular expression of TNF-alpha, (TNF receptor-associated death domain protein)TRADD, RIP(receptor-interacting protein) and TRAF-2 (TNF receptor-associated factor-) was significantly up-regulated in Lupus nephritis (PMID:19151112)
- Data show that the polymorphisms of LTA (rs1041981) and RIPK1 (rs2272990) may correlate with TTP in patients with DLBCL treated with R-CHOP. (PMID:19629486)
- RIP1 is important in maintaining resistance to TRAIL-induced apoptosis in breast tumor cells and highlight the potential therapeutic benefit of the combination of Hsp90 inhibitors and TRAIL against breast tumor cells. (PMID:19632771)
- RIP1 is necessary for the most efficient activation of downstream caspases by Fas when treated with membrane-bound Fas ligand, but not with agonistic antibodies or cross-linked soluble Fas ligand. (PMID:19641134)
- Both RIP and caspase-8 may play important roles in the occurrence and progression of oral squamous cell carcinoma and oral precancerous lesions. (PMID:19778795)
- USP21 plays an important role in the down-regulation of TNFalpha-induced NF-kappaB activation through deubiquitinating RIP1. (PMID:19910467)
- RIP1 and RIP3 have roles in TNF-induced necrosis (PMID:20354226)
- Data show that miR-155 can inhibit necrosis and improve cell survival by repressing the receptor interacting protein1, RIP1, without affecting cardiomyogenic differentiation potential. (PMID:20550618)
- The RIPK1 and CASP7 polymorphisms can be considered as possible prognostic markers for survival after curative resection in patients with colorectal cancer. (PMID:20567846)
- Results indicate an important role of RIP1 in apoptosis induced by combined treatment with TNFalpha and MeBS. (PMID:20825417)
- The authors demonstrate that c-IAP1 and UbcH5 family promote K11-linked polyubiquitination of receptor-interacting protein 1 (RIP1) in vitro and in vivo. (PMID:21113135)
- RIP1-dependent caspase activation contributes to polyinosinic-polycytidylic acid-induced soluble tumor necrosis factor receptor 1 (TNFR1) shedding indicative of innate immune responses to viral infections in human airway epithelial (NCI-H292) cells. (PMID:21148036)
- TNFalpha-duced NF-kappaB activation is attenuated by RIP1 through stabilization of TRAF2. (PMID:21266470)
- The death domain kinase RIP1 links the immunoregulatory CD40 receptor to apoptotic signaling in carcinomas (PMID:21282461)
Cross-species orthologs
3 orthologs
| Organism | Symbol | Gene ID |
|---|---|---|
| danio_rerio | ripk1l | ENSDARG00000006677 |
| mus_musculus | Ripk1 | ENSMUSG00000021408 |
| rattus_norvegicus | Ripk1 | ENSRNOG00000017787 |
Paralogs (23): MAP3K9 (ENSG00000006432), TESK2 (ENSG00000070759), MAP3K13 (ENSG00000073803), ARAF (ENSG00000078061), MAP3K20 (ENSG00000091436), RIPK2 (ENSG00000104312), LIMK1 (ENSG00000106683), TESK1 (ENSG00000107140), TNNI3K (ENSG00000116783), RIPK3 (ENSG00000129465), MAP3K10 (ENSG00000130758), RAF1 (ENSG00000132155), MAP3K12 (ENSG00000139625), KSR1 (ENSG00000141068), MAP3K21 (ENSG00000143674), BRAF (ENSG00000157764), ILK (ENSG00000166333), MLKL (ENSG00000168404), KSR2 (ENSG00000171435), MOS (ENSG00000172680), MAP3K11 (ENSG00000173327), LIMK2 (ENSG00000182541), LRRK2 (ENSG00000188906)
Protein
Protein identifiers
Receptor-interacting serine/threonine-protein kinase 1 — Q13546 (reviewed: Q13546)
Alternative names: Cell death protein RIP, Receptor-interacting protein 1
All UniProt accessions (3): Q13546, A0A7I2V404, A0A7I2V5Y1
UniProt curated annotations — full annotation on UniProt →
Function. Serine-threonine kinase which is a key regulator of TNF-mediated apoptosis, necroptosis and inflammatory pathways. Exhibits kinase activity-dependent functions that regulate cell death and kinase-independent scaffold functions regulating inflammatory signaling and cell survival. Has kinase-independent scaffold functions: upon binding of TNF to TNFR1, RIPK1 is recruited to the TNF-R1 signaling complex (TNF-RSC also known as complex I) where it acts as a scaffold protein promoting cell survival, in part, by activating the canonical NF-kappa-B pathway. Kinase activity is essential to regulate necroptosis and apoptosis, two parallel forms of cell death: upon activation of its protein kinase activity, regulates assembly of two death-inducing complexes, namely complex IIa (RIPK1-FADD-CASP8), which drives apoptosis, and the complex IIb (RIPK1-RIPK3-MLKL), which drives necroptosis. RIPK1 is required to limit CASP8-dependent TNFR1-induced apoptosis. In normal conditions, RIPK1 acts as an inhibitor of RIPK3-dependent necroptosis, a process mediated by RIPK3 component of complex IIb, which catalyzes phosphorylation of MLKL upon induction by ZBP1. Inhibits RIPK3-mediated necroptosis via FADD-mediated recruitment of CASP8, which cleaves RIPK1 and limits TNF-induced necroptosis. Required to inhibit apoptosis and necroptosis during embryonic development: acts by preventing the interaction of TRADD with FADD thereby limiting aberrant activation of CASP8. In addition to apoptosis and necroptosis, also involved in inflammatory response by promoting transcriptional production of pro-inflammatory cytokines, such as interleukin-6 (IL6). Phosphorylates RIPK3: RIPK1 and RIPK3 undergo reciprocal auto- and trans-phosphorylation. Phosphorylates DAB2IP at ‘Ser-728’ in a TNF-dependent manner, and thereby activates the MAP3K5-JNK apoptotic cascade. Required for ZBP1-induced NF-kappa-B activation in response to DNA damage.
Subunit / interactions. Homodimer. Interacts (via RIP homotypic interaction motif) with RIPK3 (via RIP homotypic interaction motif); this interaction induces RIPK1 phosphorylation and formation of a RIPK1-RIPK3 necroptosis-inducing complex. Upon TNF-induced necrosis, the RIPK1-RIPK3 dimer further interacts with PGAM5 and MLKL; the formation of this complex leads to PGAM5 phosphorylation and increase in PGAM5 phosphatase activity. Interacts (via the death domain) with TNFRSF6 (via the death domain) and TRADD (via the death domain). Is recruited by TRADD to TNFRSF1A in a TNF-dependent process. Binds RNF216, EGFR, IKBKG, TRAF1, TRAF2 and TRAF3. Interacts with BNLF1. Interacts with SQSTM1 upon TNF stimulation. May interact with MAVS/IPS1. Interacts with ZFAND5. Interacts with RBCK1. Interacts with ZBP1. Interacts with BIRC2/c-IAP1, BIRC3/c-IAP2 and XIAP/BIRC4. Interacts (via kinase domain) with DAB2IP (via Ras-GAP domain); the interaction occurs in a TNF-dependent manner. Interacts with ARHGEF2. Interacts (via protein kinase domain) with RFFL; involved in RIPK1 ubiquitination. Interacts with RNF34; involved in RIPK1 ubiquitination (Ref.35). Interacts with TICAM1 and this interaction is enhanced in the presence of WDFY1. Interacts with PELI1. Interacts (via death domain) with CRADD (via death domain); the interaction is direct. Component of complex IIa composed of at least RIPK1, FADD and CASP8. Component of the AIM2 PANoptosome complex, a multiprotein complex that drives inflammatory cell death (PANoptosis). Interacts with MAP3K7, CFLAR, CASP8, FADD and NEMO. Interacts with TAX1BP1; this interaction negatively regulates RIPK1 ubiquitination. Interacts with GRB2. Interacts with DDX24; this interaction disrupts RLR signaling activation of IFN-dependent transcription factor IRF7. (Microbial infection) Interacts with mumps virus protein SH; this interaction inhibits downstream NF-kappa-B pathway activation. (Microbial infection) Interacts with Murid herpesvirus 1 protein RIR1. (Microbial infection) Interacts (via RIP homotypic interaction motif) with herpes simplex virus 1/HHV-1 protein RIR1/ICP6 (via RIP homotypic interaction motif); this interaction prevents necroptosis activation. (Microbial infection) Interacts (via RIP homotypic interaction motif) with herpes simplex virus 2/HHV-2 protein RIR1/ICP10 (via RIP homotypic interaction motif); this interaction prevents necroptosis activation.
Subcellular location. Cytoplasm. Cell membrane.
Post-translational modifications. (Microbial infection) Proteolytically cleaved by S.flexneri OspD3 within the RIP homotypic interaction motif (RHIM), leading to its degradation and inhibition of necroptosis. Proteolytically cleaved by CASP8 at Asp-324. Cleavage is crucial for limiting TNF-induced apoptosis, necroptosis and inflammatory response. Cleavage abolishes NF-kappa-B activation and enhances the interaction of TRADD with FADD. Proteolytically cleaved by CASP6 during intrinsic apoptosis. RIPK1 and RIPK3 undergo reciprocal auto- and trans-phosphorylation. Phosphorylation of Ser-161 by RIPK3 is necessary for the formation of the necroptosis-inducing complex. Phosphorylation at Ser-25 represses its kinase activity and consequently prevents TNF-mediated RIPK1-dependent cell death. Phosphorylated at Ser-320 by MAP3K7 which requires prior ubiquitination with ‘Lys-63’-linked chains by BIRC2/c-IAP1 and BIRC3/c-IAP2. This phosphorylation positively regulates RIPK1 interaction with RIPK3 to promote necroptosis but negatively regulates RIPK1 kinase activity and its interaction with FADD to mediate apoptosis. Deubiquitinated by USP7; this modification is required for TNF-induced apoptosis. Ubiquitinated with ‘Lys-11’-, ‘Lys-48’-, ‘Lys-63’- and linear-linked type ubiquitin (PubMed:15258597, PubMed:16603398, PubMed:17703191, PubMed:18450452, PubMed:21455173, PubMed:21931591, PubMed:29883609, Ref.35). Polyubiquitination with ‘Lys-63’-linked chains by TRAF2 induces association with the IKK complex. Deubiquitination of ‘Lys-63’-linked chains and polyubiquitination with ‘Lys-48’-linked chains by TNFAIP3 leads to RIPK1 proteasomal degradation and consequently down-regulates TNF-induced NF-kappa-B signaling. ‘Lys-48’-linked polyubiquitination by RFFL or RNF34 also promotes proteasomal degradation and negatively regulates TNF-induced NF-kappa-B signaling (PubMed:18450452, Ref.35). Linear polyubiquitinated; the head-to-tail linear polyubiquitination (‘Met-1’-linked) is mediated by the LUBAC complex and decreases protein kinase activity. Deubiquitination of linear polyubiquitin by CYLD promotes the kinase activity. Polyubiquitinated with ‘Lys-48’ and ‘Lys-63’-linked chains by BIRC2/c-IAP1 and BIRC3/c-IAP2, leading to activation of NF-kappa-B. Ubiquitinated with ‘Lys-63’-linked chains by PELI1. Ubiquitination at Lys-377 with ‘Lys-63’-linked chains by BIRC2/c-IAP1 and BIRC3/c-IAP2 is essential for its phosphorylation at Ser-320 mediated by MAP3K7. This ubiquitination is required for NF-kB activation, suppresses RIPK1 kinase activity and plays a critical role in preventing cell death during embryonic development. (Microbial infection) Glycosylated at Arg-603 by enteropathogenic E.coli protein NleB1: arginine GlcNAcylation prevents homotypic/heterotypic death domain interactions.
Disease relevance. Immunodeficiency 57 with autoinflammation (IMD57) [MIM:618108] An autosomal recessive primary immunodeficiency characterized by lymphopenia and recurrent viral, bacterial, and fungal infections. Patients exhibit early-onset inflammatory bowel disease involving the upper and lower gastrointestinal tract, and develop progressive polyarthritis. The disease is caused by variants affecting the gene represented in this entry. RIPK1-deficient immune cells from IMD57 patients have impaired proinflammatory signaling leading to dysregulated cytokine secretion and are prone to necroptosis. Autoinflammation with episodic fever and lymphadenopathy (AIEFL) [MIM:618852] An autosomal dominant immunologic disorder characterized by early onset of recurrent episodes of unexplained fever, lymphadenopathy, hepatosplenomegaly, and increased levels of inflammatory cytokines and chemokines in patient serum. The disease is caused by variants affecting the gene represented in this entry.
Activity regulation. Serine-threonine kinase activity is inhibited by linear polyubiquitination (‘Met-1’-linked) by the LUBAC complex. Inhibited by necrostatins, including necrostatin-1, necrostatin-3 and necrostatin-4.
Domain organisation. The RIP homotypic interaction motif (RHIM) mediates interaction with the RHIM motif of RIPK1. Both motifs form a hetero-amyloid serpentine fold, stabilized by hydrophobic packing and featuring an unusual Cys-Ser ladder of alternating Ser (from RIPK1) and Cys (from RIPK3). The death domain mediates dimerization and activation of its kinase activity during necroptosis and apoptosis. It engages other DD-containing proteins as well as a central (intermediate) region important for NF-kB activation and RHIM-dependent signaling.
Similarity. Belongs to the protein kinase superfamily. TKL Ser/Thr protein kinase family.
Isoforms (2)
| UniProt ID | Names | Canonical? |
|---|---|---|
| Q13546-1 | 1 | yes |
| Q13546-2 | 2 |
RefSeq proteins (7): NP_001303990, NP_001341859, NP_001341860, NP_001341861, NP_001341862, NP_001341863, NP_003795 (=MANE)
Domains & families (InterPro)
| ID | Name | Type |
|---|---|---|
| IPR000488 | Death_dom | Domain |
| IPR000719 | Prot_kinase_dom | Domain |
| IPR001245 | Ser-Thr/Tyr_kinase_cat_dom | Domain |
| IPR008271 | Ser/Thr_kinase_AS | Active_site |
| IPR011009 | Kinase-like_dom_sf | Homologous_superfamily |
| IPR011029 | DEATH-like_dom_sf | Homologous_superfamily |
| IPR037934 | RIP1_Death | Domain |
| IPR051681 | Ser/Thr_Kinases-Pseudokinases | Family |
Pfam: PF00531, PF07714
Enzyme classification (BRENDA):
- EC 2.7.10.2 — non-specific protein-tyrosine kinase (BRENDA: 41 organisms, 396 substrates, 479 inhibitors, 43 Km, 32 kcat entries)
Substrate kinetics (BRENDA)
6 substrates with measured Km, best-characterized 6. Km ranges are aggregated across organisms/conditions.
| Substrate | Km (mM) | Measurements |
|---|---|---|
| ATP | 0.014–17.64 | 12 |
| [KDSRC KINASE]-L-TYROSINE | 0.0057–0.24 | 12 |
| POLY(GLU4-TYR) | 0.018–0.659 | 10 |
| EEEEYIQ[DP]-8-HYDROXY-5-(N,N-DIMETHYLSULFONAMIDO | 0.057 | 1 |
| S1 PEPTIDE | 0.037 | 1 |
| EEEEY | — | 0 |
Catalyzed reactions (Rhea), 2 shown:
- L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP + H(+) (RHEA:17989)
- L-threonyl-[protein] + ATP = O-phospho-L-threonyl-[protein] + ADP + H(+) (RHEA:46608)
UniProt features (94 total): helix 25, strand 14, sequence variant 12, modified residue 10, mutagenesis site 10, turn 4, region of interest 3, sequence conflict 3, domain 2, binding site 2, compositionally biased region 2, chain 1, site 1, glycosylation site 1, cross-link 1, splice variant 1, short sequence motif 1, active site 1
Structure
Experimental structures (PDB)
39 structures, top 30 by resolution.
| PDB | Method | Resolution (Å) |
|---|---|---|
| 5ZMZ | X-RAY DIFFRACTION | 1.4 |
| 6AC5 | X-RAY DIFFRACTION | 1.45 |
| 4ITJ | X-RAY DIFFRACTION | 1.8 |
| 6NW2 | X-RAY DIFFRACTION | 2 |
| 7FD0 | X-RAY DIFFRACTION | 2 |
| 24IB | X-RAY DIFFRACTION | 2.05 |
| 9Q31 | X-RAY DIFFRACTION | 2.05 |
| 6NYH | X-RAY DIFFRACTION | 2.1 |
| 9GTY | X-RAY DIFFRACTION | 2.15 |
| 7FCZ | X-RAY DIFFRACTION | 2.21 |
| 5HX6 | X-RAY DIFFRACTION | 2.23 |
| 4ITH | X-RAY DIFFRACTION | 2.25 |
| 9GTG | X-RAY DIFFRACTION | 2.25 |
| 8I2N | X-RAY DIFFRACTION | 2.29 |
| 9HY9 | X-RAY DIFFRACTION | 2.29 |
| 9MZY | X-RAY DIFFRACTION | 2.32 |
| 7XMK | X-RAY DIFFRACTION | 2.38 |
| 9Q32 | X-RAY DIFFRACTION | 2.49 |
| 6C4D | X-RAY DIFFRACTION | 2.52 |
| 9MZX | X-RAY DIFFRACTION | 2.53 |
| 5TX5 | X-RAY DIFFRACTION | 2.56 |
| 4NEU | X-RAY DIFFRACTION | 2.57 |
| 9HR6 | ELECTRON MICROSCOPY | 2.57 |
| 6C3E | X-RAY DIFFRACTION | 2.6 |
| 7YDX | X-RAY DIFFRACTION | 2.64 |
| 9MZZ | X-RAY DIFFRACTION | 2.68 |
| 24IC | X-RAY DIFFRACTION | 2.7 |
| 6OCQ | X-RAY DIFFRACTION | 2.79 |
| 7CJB | X-RAY DIFFRACTION | 2.8 |
| 4ITI | X-RAY DIFFRACTION | 2.86 |
Predicted structure (AlphaFold)
| Model | pLDDT | Fraction very-high |
|---|---|---|
| AF-Q13546-F1 | 70.38 | 0.33 |
Functional residue map
Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.
Catalytic / active sites (2): 324–325 (cleavage; by casp8); 138 (proton acceptor)
Ligand- & substrate-binding residues (2): 23–31; 45
Post-translational modifications (11): 6, 20, 25, 161, 166, 303, 320, 331, 333, 384, 377
Glycosylation sites (1): 603
Mutagenesis-validated functional residues (10):
| Position | Phenotype |
|---|---|
| 25 | phophomimetic mutant. significant loss of kinase activity. |
| 45 | abolishes kinase activity. |
| 161 | decreases ripk1 kinase activity. |
| 161 | no effect on ripk1 autophosphorylation. |
| 324 | abolishes cleavage by caspase-8. |
| 377 | abolishes rip-mediated nf-kappa-b activation. |
| 536 | strongly reduced homodimerization and interaction with ripk3. |
| 539–542 | abolished cleavage by s.flexneri ospd3. |
| 599 | blocks homodimerization, necroptosis and apoptosis. |
| 603 | abolished glcnacylation by e.coli nleb1. |
Function
Pathways and Gene Ontology
Reactome pathways
24 pathways
| ID | Pathway |
|---|---|
| R-HSA-140534 | Caspase activation via Death Receptors in the presence of ligand |
| R-HSA-168927 | TICAM1, RIP1-mediated IKK complex recruitment |
| R-HSA-1810476 | RIP-mediated NFkB activation via ZBP1 |
| R-HSA-2562578 | TRIF-mediated programmed cell death |
| R-HSA-3295583 | TRP channels |
| R-HSA-3371378 | Regulation by c-FLIP |
| R-HSA-5213460 | RIPK1-mediated regulated necrosis |
| R-HSA-5218900 | CASP8 activity is inhibited |
| R-HSA-5357786 | TNFR1-induced proapoptotic signaling |
| R-HSA-5357905 | Regulation of TNFR1 signaling |
| R-HSA-5357956 | TNFR1-induced NF-kappa-B signaling pathway |
| R-HSA-5675482 | Regulation of necroptotic cell death |
| R-HSA-5689880 | Ub-specific processing proteases |
| R-HSA-5689896 | Ovarian tumor domain proteases |
| R-HSA-69416 | Dimerization of procaspase-8 |
| R-HSA-75893 | TNF signaling |
| R-HSA-9013957 | TLR3-mediated TICAM1-dependent programmed cell death |
| R-HSA-933543 | NF-kB activation through FADD/RIP-1 pathway mediated by caspase-8 and -10 |
| R-HSA-937041 | IKK complex recruitment mediated by RIP1 |
| R-HSA-9679191 | Potential therapeutics for SARS |
| R-HSA-9686347 | Microbial modulation of RIPK1-mediated regulated necrosis |
| R-HSA-9692913 | SARS-CoV-1-mediated effects on programmed cell death |
| R-HSA-9693928 | Defective RIPK1-mediated regulated necrosis |
| R-HSA-9920951 | Dengue virus modulates apoptosis |
MSigDB gene sets: 0 (showing top):
GO Biological Process (56): positive regulation of protein phosphorylation (GO:0001934), apoptotic process (GO:0006915), inflammatory response (GO:0006954), response to oxidative stress (GO:0006979), canonical NF-kappaB signal transduction (GO:0007249), positive regulation of gene expression (GO:0010628), protein catabolic process (GO:0030163), positive regulation of interleukin-8 production (GO:0032757), positive regulation of tumor necrosis factor production (GO:0032760), tumor necrosis factor-mediated signaling pathway (GO:0033209), response to tumor necrosis factor (GO:0034612), intracellular signal transduction (GO:0035556), peptidyl-serine autophosphorylation (GO:0036289), positive regulation of apoptotic process (GO:0043065), negative regulation of apoptotic process (GO:0043066), positive regulation of programmed cell death (GO:0043068), positive regulation of canonical NF-kappaB signal transduction (GO:0043123), negative regulation of canonical NF-kappaB signal transduction (GO:0043124), positive regulation of neuron apoptotic process (GO:0043525), positive regulation of macrophage differentiation (GO:0045651), positive regulation of transcription by RNA polymerase II (GO:0045944), positive regulation of JNK cascade (GO:0046330), protein autophosphorylation (GO:0046777), positive regulation of inflammatory response (GO:0050729), obsolete positive regulation of NF-kappaB transcription factor activity (GO:0051092), positive regulation of necroptotic process (GO:0060545), negative regulation of necroptotic process (GO:0060546), positive regulation of programmed necrotic cell death (GO:0062100), positive regulation of interleukin-6-mediated signaling pathway (GO:0070105), T cell apoptotic process (GO:0070231), necroptotic process (GO:0070266), cellular response to hydrogen peroxide (GO:0070301), cellular response to tumor necrosis factor (GO:0071356), cellular response to growth factor stimulus (GO:0071363), extrinsic apoptotic signaling pathway (GO:0097191), programmed necrotic cell death (GO:0097300), ripoptosome assembly (GO:0097343), necroptotic signaling pathway (GO:0097527), positive regulation of execution phase of apoptosis (GO:1900119), ripoptosome assembly involved in necroptotic process (GO:1901026)
GO Molecular Function (17): protein kinase activity (GO:0004672), protein serine/threonine kinase activity (GO:0004674), JUN kinase kinase kinase activity (GO:0004706), death receptor binding (GO:0005123), ATP binding (GO:0005524), ubiquitin protein ligase binding (GO:0031625), signaling adaptor activity (GO:0035591), identical protein binding (GO:0042802), protein homodimerization activity (GO:0042803), protein-containing complex binding (GO:0044877), death domain binding (GO:0070513), protein serine kinase activity (GO:0106310), protein serine/threonine kinase binding (GO:0120283), nucleotide binding (GO:0000166), protein binding (GO:0005515), kinase activity (GO:0016301), transferase activity (GO:0016740)
GO Cellular Component (10): cytoplasm (GO:0005737), mitochondrion (GO:0005739), cytosol (GO:0005829), plasma membrane (GO:0005886), endosome membrane (GO:0010008), death-inducing signaling complex (GO:0031264), protein-containing complex (GO:0032991), signaling receptor complex (GO:0043235), ripoptosome (GO:0097342), membrane (GO:0016020)
Reactome top-level categories
Rollup of top-14 pathways:
| Category | Pathways |
|---|---|
| TNF signaling | 3 |
| Toll Like Receptor 3 (TLR3) Cascade | 2 |
| TRIF (TICAM1)-mediated TLR4 signaling | 2 |
| Caspase activation via Death Receptors in the presence of ligand | 2 |
| Deubiquitination | 2 |
| Caspase activation via extrinsic apoptotic signalling pathway | 1 |
| ZBP1(DAI) mediated induction of type I IFNs | 1 |
| Stimuli-sensing channels | 1 |
| Regulated Necrosis | 1 |
| Regulation of necroptotic cell death | 1 |
| RIPK1-mediated regulated necrosis | 1 |
| Death Receptor Signaling | 1 |
| DDX58/IFIH1-mediated induction of interferon-alpha/beta | 1 |
| SARS-CoV Infections | 1 |
GO top-level categories
Rollup of top GO terms by namespace:
| Category | Terms |
|---|---|
| cellular anatomical structure | 3 |
| programmed cell death | 2 |
| intracellular anatomical structure | 2 |
| apoptotic process | 2 |
| regulation of apoptotic process | 2 |
| canonical NF-kappaB signal transduction | 2 |
| regulation of canonical NF-kappaB signal transduction | 2 |
| protein kinase activity | 2 |
| binding | 2 |
| cytoplasm | 2 |
| regulation of protein phosphorylation | 1 |
| protein phosphorylation | 1 |
| positive regulation of protein modification process | 1 |
| positive regulation of phosphorylation | 1 |
| apoptotic signaling pathway | 1 |
| execution phase of apoptosis | 1 |
| defense response | 1 |
| response to stress | 1 |
| intracellular signaling cassette | 1 |
| gene expression | 1 |
| regulation of gene expression | 1 |
| positive regulation of macromolecule biosynthetic process | 1 |
| macromolecule catabolic process | 1 |
| protein metabolic process | 1 |
| positive regulation of cytokine production | 1 |
| interleukin-8 production | 1 |
| regulation of interleukin-8 production | 1 |
| tumor necrosis factor production | 1 |
| regulation of tumor necrosis factor production | 1 |
| positive regulation of tumor necrosis factor superfamily cytokine production | 1 |
| cytokine-mediated signaling pathway | 1 |
| cellular response to tumor necrosis factor | 1 |
| response to cytokine | 1 |
| signal transduction | 1 |
| peptidyl-serine phosphorylation | 1 |
| protein autophosphorylation | 1 |
| positive regulation of programmed cell death | 1 |
| negative regulation of programmed cell death | 1 |
| regulation of programmed cell death | 1 |
| positive regulation of cellular process | 1 |
Protein interactions and networks
STRING
3240 interactions, top by confidence (×1000):
| Protein A | Protein B | Partner UniProt | Score |
|---|---|---|---|
| RIPK1 | FADD | Q13158 | 998 |
| RIPK1 | CASP8 | Q14790 | 998 |
| RIPK1 | TRADD | Q15628 | 998 |
| RIPK1 | TNFRSF1A | P19438 | 997 |
| RIPK1 | BIRC2 | Q13490 | 996 |
| RIPK1 | CFLAR | O15519 | 995 |
| RIPK1 | TRAF2 | Q12933 | 994 |
| RIPK1 | IKBKG | Q9Y6K9 | 994 |
| RIPK1 | BIRC3 | Q13489 | 993 |
| RIPK1 | TRAF5 | O00463 | 992 |
| RIPK1 | RIPK3 | Q9Y572 | 989 |
| RIPK1 | MLKL | Q8NB16 | 989 |
| RIPK1 | TRAF6 | Q9Y4K3 | 987 |
| RIPK1 | TAB2 | Q9NYJ8 | 982 |
| RIPK1 | IFNB1 | P01574 | 971 |
IntAct
280 interactions, top by confidence:
| A | B | Type | Score |
|---|---|---|---|
| CASP8 | FADD | psi-mi:“MI:0914”(association) | 0.980 |
| IKBKG | IKBKB | psi-mi:“MI:0914”(association) | 0.980 |
| CASP8 | FADD | psi-mi:“MI:0915”(physical association) | 0.980 |
| RIPK1 | RIPK3 | psi-mi:“MI:0914”(association) | 0.970 |
| RIPK3 | RIPK1 | psi-mi:“MI:0915”(physical association) | 0.970 |
| RIPK1 | RIPK3 | psi-mi:“MI:0915”(physical association) | 0.970 |
| RIPK1 | RIPK3 | psi-mi:“MI:0217”(phosphorylation reaction) | 0.970 |
| RIPK3 | RIPK1 | psi-mi:“MI:0914”(association) | 0.970 |
| TNF | TNFRSF1A | psi-mi:“MI:0914”(association) | 0.960 |
| CASP8 | RIPK1 | psi-mi:“MI:0914”(association) | 0.960 |
BioGRID (609): RIPK1 (Affinity Capture-Western), RIPK1 (Biochemical Activity), RIPK1 (Affinity Capture-Western), RFFL (Affinity Capture-Western), RIPK1 (Affinity Capture-Western), RIPK1 (Two-hybrid), RIPK1 (Two-hybrid), RIPK1 (Two-hybrid), RIPK1 (Reconstituted Complex), RIPK1 (Biochemical Activity), RIPK1 (Affinity Capture-Western), RIPK1 (Affinity Capture-Western), RIPK1 (Affinity Capture-Western), UBC (Affinity Capture-Western), UBC (Affinity Capture-Western)
ESM2 similar proteins: A1YG61, A2T737, A4IGQ8, B5XCB8, O60934, O70273, P28715, Q08B72, Q0III0, Q13546, Q28J92, Q2KJE0, Q32LN0, Q3B8D4, Q3T0G1, Q3US16, Q4R3Q6, Q5R4U3, Q5RCE4, Q5RCV3, Q5SZJ8, Q5U208, Q5U560, Q5VVJ2, Q60855, Q69Z66, Q6DDT6, Q6DIN8, Q6IR68, Q6PFX2, Q6TGZ4, Q7L4P6, Q7ZYM8, Q86VP1, Q86VV4, Q8BSV3, Q8C6D4, Q8CHW1, Q8IW35, Q8N302
Diamond homologs: A0A509AH51, A1CAF0, A1CL96, A1D624, A2QU77, A2YMV6, A8BPK8, B1H3E1, B5VNQ3, C4YGK0, D0Z5N4, O18209, O19004, O34507, O45797, O61661, P04627, P09251, P0CS76, P0CS77, P10398, P10533, P12965, P14056, P15056, P19026, P23293, P27966, P28028, P28926, P32516, P32866, P34908, P41808, P51953, P52304, P84390, Q00772, Q01577, Q04543
SIGNOR signaling
64 interactions.
| A | Effect | B | Mechanism |
|---|---|---|---|
| RIPK1 | “up-regulates activity” | CASP8 | binding |
| RIPK1 | “up-regulates activity” | MAP3K1 | phosphorylation |
| RIPK1 | up-regulates | MAP3K1 | phosphorylation |
| RIPK1 | up-regulates | Necrosis | |
| RIPK1 | “up-regulates activity” | TAB2 | binding |
| BIRC2 | “up-regulates activity” | RIPK1 | ubiquitination |
| BIRC3 | “up-regulates activity” | RIPK1 | ubiquitination |
| RIPK1 | “up-regulates activity” | IKBKG | binding |
| RIPK1 | “up-regulates activity” | TAB3 | binding |
| FADD | “up-regulates activity” | RIPK1 | binding |
| RIPK1 | “up-regulates activity” | FAS | binding |
| RIPK1 | up-regulates | TNFRSF10A | |
| TRAF2 | “up-regulates activity” | RIPK1 | ubiquitination |
| 5-(1H-indol-3-ylmethyl)-3-methyl-2-sulfanylidene-4-imidazolidinone | down-regulates | RIPK1 | “chemical inhibition” |
| TICAM1 | “up-regulates activity” | RIPK1 | binding |
| RIPK1 | “up-regulates activity” | TRAF6 | binding |
| RIPK1 | “up-regulates activity” | DAB2IP | phosphorylation |
| RIPK1 | “up-regulates activity” | MAP3K7 | binding |
| TRAF2 | up-regulates | RIPK1 | |
| “Caspase 8 complex” | “down-regulates activity” | RIPK1 | cleavage |
| TNFAIP3 | “down-regulates quantity” | RIPK1 | ubiquitination |
| ponatinib | “down-regulates activity” | RIPK1 | “chemical inhibition” |
Enriched among interaction partners
Reactome pathways and GO biological processes over-represented among this gene’s 104 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 |
|---|---|---|---|
| RIPK1-mediated regulated necrosis | 11 | 68.8× | 3e-16 |
| TICAM1, RIP1-mediated IKK complex recruitment | 8 | 65.9× | 1e-11 |
| Caspase activation via Death Receptors in the presence of ligand | 6 | 62.6× | 1e-08 |
| TNFR1-induced proapoptotic signaling | 10 | 60.2× | 4e-14 |
| Regulation of necroptotic cell death | 10 | 60.2× | 4e-14 |
| TNFR1-induced NF-kappa-B signaling pathway | 13 | 59.8× | 3e-18 |
| IKK complex recruitment mediated by RIP1 | 8 | 54.4× | 6e-11 |
| Regulation of TNFR1 signaling | 17 | 52.1× | 6e-23 |
GO biological processes:
| GO term | Partners | Fold | FDR |
|---|---|---|---|
| non-canonical NF-kappaB signal transduction | 5 | 48.4× | 4e-06 |
| protein refolding | 6 | 43.0× | 7e-07 |
| tumor necrosis factor-mediated signaling pathway | 11 | 41.8× | 1e-12 |
| regulation of tumor necrosis factor-mediated signaling pathway | 5 | 40.4× | 1e-05 |
| canonical NF-kappaB signal transduction | 9 | 37.9× | 5e-10 |
| extrinsic apoptotic signaling pathway via death domain receptors | 8 | 36.9× | 7e-09 |
| negative regulation of canonical NF-kappaB signal transduction | 11 | 21.7× | 6e-10 |
| extrinsic apoptotic signaling pathway | 6 | 21.1× | 3e-05 |
Disease & clinical
Cancer significance
From intOGen — cancer-driver classification: loss-of-function (tumor-suppressor-like) across 1 cancer types — CLLSLL.
Clinical variants and AI predictions
ClinVar
588 variants total. Per-class counts are floors (≥ shown; pagination cap):
| Classification | Count (floor) |
|---|---|
| Pathogenic | 22 |
| Likely pathogenic | 7 |
| Uncertain significance | 329 |
| Likely benign | 187 |
| Benign | 12 |
Top pathogenic / likely-pathogenic (29)
| Variant ID | HGVS | Classification |
|---|---|---|
| 1350924 | NC_000006.11:g.(?3077058)(3078189_?)del | Pathogenic |
| 1424981 | NM_001354930.2(RIPK1):c.187G>T (p.Glu63Ter) | Pathogenic |
| 1455831 | NM_001354930.2(RIPK1):c.1632C>G (p.Tyr544Ter) | Pathogenic |
| 1456594 | NC_000006.11:g.(?3083299)(3085662_?)del | Pathogenic |
| 1457300 | NM_001354930.2(RIPK1):c.528_532del (p.Arg177fs) | Pathogenic |
| 1459670 | NC_000006.11:g.(?3104439)(3106305_?)del | Pathogenic |
| 151603 | GRCh38/hg38 6p25.3-22.3(chr6:155807-17058414)x3 | Pathogenic |
| 1949108 | NM_001354930.2(RIPK1):c.388del (p.His130fs) | Pathogenic |
| 2822654 | NM_001354930.2(RIPK1):c.569_585del (p.Leu190fs) | Pathogenic |
| 2858656 | NM_001354930.2(RIPK1):c.1542dup (p.Pro515fs) | Pathogenic |
| 3246172 | NC_000006.11:g.(?3083299)(3106305_?)del | Pathogenic |
| 3621187 | NM_001354930.2(RIPK1):c.775G>T (p.Glu259Ter) | Pathogenic |
| 561164 | NM_001354930.2(RIPK1):c.867_870del (p.Phe288_Tyr289insTer) | Pathogenic |
| 561165 | NM_001354930.2(RIPK1):c.688_688+20del | Pathogenic |
| 561166 | NM_001354930.2(RIPK1):c.460-133_689-244del | Pathogenic |
| 598789 | NM_001354930.2(RIPK1):c.1278C>A (p.Tyr426Ter) | Pathogenic |
| 598791 | NM_001354930.2(RIPK1):c.1802G>A (p.Cys601Tyr) | Pathogenic |
| 870218 | NM_001354930.2(RIPK1):c.970G>A (p.Asp324Asn) | Pathogenic |
| 870219 | NM_001354930.2(RIPK1):c.970G>C (p.Asp324His) | Pathogenic |
| 870220 | NM_001354930.2(RIPK1):c.970G>T (p.Asp324Tyr) | Pathogenic |
| 870221 | NM_001354930.2(RIPK1):c.971A>T (p.Asp324Val) | Pathogenic |
| 981836 | NM_001354930.2(RIPK1):c.1802_1805del (p.Cys601fs) | Pathogenic |
| 1498963 | NM_001354930.2(RIPK1):c.322-1G>C | Likely pathogenic |
| 1690605 | NM_001354930.2(RIPK1):c.1458_1459del (p.Arg487fs) | Likely pathogenic |
| 2809856 | NM_001354930.2(RIPK1):c.915+1G>A | Likely pathogenic |
| 3246170 | NC_000006.11:g.(?3081193)(3081370_?)del | Likely pathogenic |
| 3630393 | NM_001354930.2(RIPK1):c.1576+2T>G | Likely pathogenic |
| 3765421 | NM_001354930.2(RIPK1):c.1577-1G>A | Likely pathogenic |
| 4154692 | NM_001354930.2(RIPK1):c.971A>G (p.Asp324Gly) | Likely pathogenic |
SpliceAI
1951 predictions. Top by Δscore:
| Variant | Effect | Δscore |
|---|---|---|
| 6:3076911:A:T | donor_gain | 1.0000 |
| 6:3076988:G:GG | donor_gain | 1.0000 |
| 6:3077872:G:GT | donor_gain | 1.0000 |
| 6:3077872:G:T | donor_gain | 1.0000 |
| 6:3077931:CCGAG:C | donor_loss | 1.0000 |
| 6:3077932:CGAGG:C | donor_loss | 1.0000 |
| 6:3077933:GAGG:G | donor_loss | 1.0000 |
| 6:3077934:AG:A | donor_loss | 1.0000 |
| 6:3077935:GGTA:G | donor_loss | 1.0000 |
| 6:3077936:GTAGA:G | donor_loss | 1.0000 |
| 6:3077937:T:A | donor_loss | 1.0000 |
| 6:3083246:G:GT | donor_gain | 1.0000 |
| 6:3083272:T:TA | donor_gain | 1.0000 |
| 6:3083273:A:AA | donor_gain | 1.0000 |
| 6:3083310:GAAA:G | donor_gain | 1.0000 |
| 6:3083311:A:T | donor_gain | 1.0000 |
| 6:3083312:AAGT:A | donor_loss | 1.0000 |
| 6:3083313:AGT:A | donor_loss | 1.0000 |
| 6:3083314:G:GG | donor_gain | 1.0000 |
| 6:3083314:G:T | donor_loss | 1.0000 |
| 6:3083315:T:G | donor_loss | 1.0000 |
| 6:3104217:A:AG | acceptor_gain | 1.0000 |
| 6:3104218:A:G | acceptor_gain | 1.0000 |
| 6:3104223:A:AG | acceptor_gain | 1.0000 |
| 6:3104224:G:GA | acceptor_gain | 1.0000 |
| 6:3104224:GAA:G | acceptor_gain | 1.0000 |
| 6:3104224:GAAA:G | acceptor_gain | 1.0000 |
| 6:3104311:TTCAG:T | donor_loss | 1.0000 |
| 6:3104312:TCAG:T | donor_loss | 1.0000 |
| 6:3104313:CAG:C | donor_loss | 1.0000 |
AlphaMissense
4492 scored. Top likely-pathogenic:
| Variant | Protein change | am_pathogenicity |
|---|---|---|
| 6:3113115:T:A | W598R | 0.998 |
| 6:3113115:T:C | W598R | 0.998 |
| 6:3113226:T:A | W635R | 0.997 |
| 6:3113226:T:C | W635R | 0.997 |
| 6:3113128:C:A | A602D | 0.996 |
| 6:3113117:G:C | W598C | 0.994 |
| 6:3113117:G:T | W598C | 0.994 |
| 6:3113281:T:C | L653P | 0.993 |
| 6:3083280:T:A | W219R | 0.992 |
| 6:3083280:T:C | W219R | 0.992 |
| 6:3113271:G:C | A650P | 0.992 |
| 6:3113218:T:C | L632P | 0.991 |
| 6:3113269:T:C | L649P | 0.989 |
| 6:3083262:A:C | S213R | 0.988 |
| 6:3083264:C:A | S213R | 0.988 |
| 6:3083264:C:G | S213R | 0.988 |
| 6:3113137:T:C | L605P | 0.987 |
| 6:3113215:T:G | M631R | 0.986 |
| 6:3113272:C:A | A650D | 0.986 |
| 6:3113215:T:A | M631K | 0.985 |
| 6:3113228:G:C | W635C | 0.985 |
| 6:3113228:G:T | W635C | 0.985 |
| 6:3113131:G:C | R603P | 0.984 |
| 6:3113116:G:C | W598S | 0.983 |
| 6:3113127:G:C | A602P | 0.983 |
| 6:3113277:G:C | A652P | 0.983 |
| 6:3113281:T:A | L653H | 0.981 |
| 6:3085372:T:A | W268R | 0.980 |
| 6:3085372:T:C | W268R | 0.980 |
| 6:3113083:T:C | L587P | 0.979 |
dbSNP variants (sampled 300 via entrez): RS1000095415 (6:3068930 T>G), RS1000126978 (6:3109862 C>G,T), RS1000148853 (6:3076986 G>C), RS1000229128 (6:3068837 C>A,T), RS1000240255 (6:3096713 C>T), RS1000247018 (6:3115621 C>G), RS1000305249 (6:3073247 TATA>T), RS1000375654 (6:3082577 T>A,G), RS1000412588 (6:3078407 G>A), RS1000485531 (6:3078305 A>T), RS1000537604 (6:3078547 T>A,C), RS1000557451 (6:3097336 G>C,T), RS1000715194 (6:3089416 A>C,G), RS1000837523 (6:3098118 G>C), RS1000902546 (6:3105149 G>A)
Disease associations
OMIM: gene MIM:603453 | disease phenotypes: MIM:618108, MIM:618852
GenCC curated gene-disease
| Disease | Classification | Inheritance |
|---|---|---|
| immunodeficiency 57 | Definitive | Autosomal recessive |
| autoinflammation with episodic fever and lymphadenopathy | Strong | Autosomal dominant |
| immune dysregulation-inflammatory bowel disease-arthritis-recurrent infections-lymphopenia syndrome | Supportive | Autosomal recessive |
ClinGen Gene-Disease Validity (1)
Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.
| Disease | Classification | Inheritance |
|---|---|---|
| immunodeficiency 57 | Definitive | AR |
Mondo (6): immunodeficiency 57 (MONDO:0020849), autoinflammation with episodic fever and lymphadenopathy (MONDO:0030018), inborn error of immunity (MONDO:0003778), IL10-related early-onset inflammatory bowel disease (MONDO:0016542), hereditary breast ovarian cancer syndrome (MONDO:0003582), immune dysregulation-inflammatory bowel disease-arthritis-recurrent infections-lymphopenia syndrome (MONDO:0033968)
Orphanet (3): Primary immunodeficiency (Orphanet:101997), Immune dysregulation-inflammatory bowel disease-arthritis-recurrent infections syndrome (Orphanet:238569), Hereditary breast and/or ovarian cancer syndrome (Orphanet:145)
HPO phenotypes
28 total (28 of 28 shown, HPO-id order):
| HPO | Term |
|---|---|
| HP:0000006 | Autosomal dominant inheritance |
| HP:0000007 | Autosomal recessive inheritance |
| HP:0000155 | Oral ulcer |
| HP:0000988 | Skin rash |
| HP:0001508 | Failure to thrive |
| HP:0001744 | Splenomegaly |
| HP:0001935 | Microcytic anemia |
| HP:0001954 | Recurrent fever |
| HP:0002014 | Diarrhea |
| HP:0002027 | Abdominal pain |
| HP:0002037 | Inflammation of the large intestine |
| HP:0002110 | Bronchiectasis |
| HP:0002205 | Recurrent respiratory infections |
| HP:0002240 | Hepatomegaly |
| HP:0002716 | Lymphadenopathy |
| HP:0002923 | Rheumatoid factor positive |
| HP:0003493 | Antinuclear antibody positivity |
| HP:0003593 | Infantile onset |
| HP:0003623 | Neonatal onset |
| HP:0004313 | Decreased circulating immunoglobulin concentration |
| HP:0005263 | Gastritis |
| HP:0005403 | Decreased total T cell count |
| HP:0006528 | Chronic lung disease |
| HP:0009789 | Perianal abscess |
| HP:0010976 | Decreased total B cell count |
| HP:0011110 | Recurrent tonsillitis |
| HP:0040218 | Reduced total natural killer cell count |
| HP:0410297 | Partial absence of specific antibody response to tetanus vaccine |
GWAS associations
2 associations (top):
| Study | Trait | p-value |
|---|---|---|
| GCST003918_6 | Idiopathic osteonecrosis of the femoral head | 5.000000e-06 |
| GCST009206_5 | Cerebral white matter volume | 3.000000e-06 |
EFO canonical traits (2, from GWAS)
| EFO ID | Trait name |
|---|---|
| EFO:1001930 | idiopathic osteonecrosis of the femoral head |
| EFO:0008320 | white matter volume measurement |
MeSH disease descriptors (2)
| Descriptor | Name | Tree numbers |
|---|---|---|
| D061325 | Hereditary Breast and Ovarian Cancer Syndrome | C04.588.180.483; C04.588.322.455.431; C04.700.517; C12.050.351.500.056.630.705.431; C12.050.351.937.418.685.431; C12.100.250.056.630.705.431; C12.900.418.685.431; C16.320.700.517; C17.800.090.500.483; C19.344.410.431; C19.391.630.705.431 |
| D007153 | Immunologic Deficiency Syndromes | C20.673 |
Drugs & pharmacology
Drug and pharmacology data
Is drug target: yes
ChEMBL targets (4): CHEMBL3885602 (PROTEIN FAMILY), CHEMBL5464 (SINGLE PROTEIN), CHEMBL5465217 (PROTEIN-PROTEIN INTERACTION), CHEMBL6066130 (PROTEIN-PROTEIN INTERACTION)
Molecules with ChEMBL bioactivity
24 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 263,504 (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 |
|---|---|---|---|
| CHEMBL1171837 | PONATINIB | 4 | 8,955 |
| CHEMBL1287853 | FEDRATINIB | 4 | 3,554 |
| CHEMBL1289926 | AXITINIB | 4 | 15,732 |
| CHEMBL1336 | SORAFENIB | 4 | 86,060 |
| CHEMBL2028663 | DABRAFENIB | 4 | 12,430 |
| CHEMBL477772 | PAZOPANIB | 4 | 15,540 |
| CHEMBL502835 | NINTEDANIB | 4 | 8,545 |
| CHEMBL535 | SUNITINIB | 4 | 79,020 |
| CHEMBL576982 | QUIZARTINIB | 4 | 4,432 |
| CHEMBL601719 | CRIZOTINIB | 4 | 14,403 |
| CHEMBL223360 | LINIFANIB | 3 | 3,925 |
| CHEMBL522892 | DOVITINIB | 3 | 4,944 |
| CHEMBL1230609 | FORETINIB | 2 | 3,096 |
| CHEMBL1721885 | SU-014813 | 2 | 363 |
| CHEMBL1738757 | REBASTINIB | 2 | 1,478 |
| CHEMBL3348846 | FEXAGRATINIB | 2 | 221 |
| CHEMBL4071864 | GSK2982772 | 2 | 483 |
| CHEMBL4861471 | ECLITASERTIB | 2 | 259 |
| CHEMBL5314462 | FLIZASERTIB | 2 | 21 |
| CHEMBL5416250 | OCADUSERTIB | 2 | 43 |
| CHEMBL558752 | RAF-265 | 2 | |
| CHEMBL572878 | TOZASERTIB | 2 | |
| CHEMBL1908397 | KW-2449 | 1 | |
| CHEMBL574738 | AST-487 | 1 |
PharmGKB: 1 entry (VIP=true, CPIC=false)
GtoPdb / IUPHAR curated pharmacology
(IUPHAR/BPS Guide to Pharmacology — expert-curated)
Target class: enzyme — Receptor interacting protein kinase (RIPK) family
Most potent curated ligand interactions (25 total), top 25:
| Ligand | Action | Affinity | Parameter |
|---|---|---|---|
| eclitasertib | Inhibition | 10.0 | pIC50 |
| oditrasertib | Inhibition | 10.0 | pIC50 |
| GSK963 | Inhibition | 9.1 | pIC50 |
| GSK2982772 | Inhibition | 9.0 | pIC50 |
| compound 21 [PMID: 24900635] | Inhibition | 8.89 | pIC50 |
| WJH-C19 | Inhibition | 8.24 | pIC50 |
| GSK3145095 | Inhibition | 8.2 | pIC50 |
| SZM679 | Inhibition | 8.07 | pKd |
| GSK'547 | Inhibition | 8.0 | pIC50 |
| RIPK1 inhibitor 22b | Inhibition | 7.96 | pIC50 |
| ponatinib | Inhibition | 7.92 | pIC50 |
| compound 27 [PMID: 24900635] | Inhibition | 7.89 | pIC50 |
| RIPA-56 | Inhibition | 7.89 | pIC50 |
| GNE684 | Inhibition | 7.68 | pKi |
| necrostatin-1s | Inhibition | 7.43 | pKd |
| ocadusertib | Inhibition | 7.4 | pIC50 |
| PN10 | Inhibition | 7.05 | pIC50 |
| SZM594 | Inhibition | 7.01 | pKd |
| SIR1-365 | Inhibition | 7.0 | pIC50 |
| flizasertib | Inhibition | 6.66 | pKi |
| 6E11 | Inhibition | 6.4 | pKd |
| TAK-632 | Inhibition | 6.32 | pKd |
| necrostatin-1 | Inhibition | 6.31 | pIC50 |
| RIPK3 inhibitor 42 | Inhibition | 5.3 | pKd |
| RIPK3 inhibitor 18 | Inhibition | 5.26 | pIC50 |
Binding affinities (BindingDB)
574 measured of 653 human assays (653 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.
| Ligand | Measure | Value | Patent |
|---|---|---|---|
| 8-(2-Amino-[1,2,4]triazolo[1,5-a]pyridin-7-yl)-2-(2-fluoro-5-(trifluoromethoxy)benzyl)-2,3,4,5-tetrahydro-1H-benzo[c]azepin-1-one 2 | IC50 | 2.7 nM | US-20250197390: FUSED HETEROCYCLIC COMPOUND, AND PREPARATION METHOD THEREFOR AND MEDICAL USE THEREOF |
| [(5S,7S)-5-(3-chlorophenyl)-7-fluoro-6,7-dihydro-5H-pyrrolo[1,2-b][1,2,4]triazol-2-yl]-cyclopropylmethanone | KI | 6.5 nM | US-12344612: Bicyclic ketone compounds and methods of use thereof |
| 5-[[3-[3-(3,5-difluorophenyl)-3,4-dihydropyrazole-2-carbonyl]-1-bicyclo[1.1.1]pentanyl]methoxy]pyrazine-2-carbonitrile | IC50 | 8.3 nM | US-20250214942: INHIBITORS OF RECEPTOR INTERACTING PROTEIN KINASE I FOR THE TREATMENT OF DISEASE |
| Cyclopropyl-[(5R,7R)-7-fluoro-5-(5-fluoro-3-pyridyl)-6,7-dihydro-5H-pyrrolo[1,2-b][1,2,4]triazol-2-yl]methanone and cyclopropyl-[(5S,7S)-7-fluoro-5-(5-fluoro-3-pyridyl)-6,7-dihydro-5H-pyrrolo[1,2-b][1,2,4]triazol-2-yl]methanone | KI | 9 nM | US-12344612: Bicyclic ketone compounds and methods of use thereof |
| 1-((3-(5-(5-cyanopyridin-3- yl)-4,5-dihydro-1H-pyrazole- 1-carbonyl)bicyclo[1.1.1]- pentan-1-yl)methyl)-1H- indazole-5-carbonitrile | IC50 | 9.1 nM | US-20250214942: INHIBITORS OF RECEPTOR INTERACTING PROTEIN KINASE I FOR THE TREATMENT OF DISEASE |
| 1-((3-(5-(3,5-difluorophenyl)- 4,5-dihydro-1H-pyrazole-1- carbonyl)bicyclo[1.1.1]pentan- 1-yl)methyl)-1H-pyrrolo[3,2- b]pyridine-5-carbonitrile | IC50 | 9.4 nM | US-20250214942: INHIBITORS OF RECEPTOR INTERACTING PROTEIN KINASE I FOR THE TREATMENT OF DISEASE |
| 1-((3-(5-(3-fluorophenyl)- 4,5-dihydro-1H-pyrazole-1- carbonyl)bicyclo[1.1.1]- pentan-1-yl)methyl)-1H- pyrazolo[4,3-b]pyridine-5- carbonitrile | IC50 | 9.6 nM | US-20250214942: INHIBITORS OF RECEPTOR INTERACTING PROTEIN KINASE I FOR THE TREATMENT OF DISEASE |
| 1-((3-(5-(3,5-difluorophenyl)- 4,5-dihydro-1H-pyrazole-1- carbonyl)bicyclo[1.1.1]- pentan-1-yl)methyl)-1H- indazole-5-carbonitrile | IC50 | 10 nM | US-20250214942: INHIBITORS OF RECEPTOR INTERACTING PROTEIN KINASE I FOR THE TREATMENT OF DISEASE |
| 5-benzyl-N-[(3S)-7-[2-(3-hydroxyoxetan-3-yl)ethynyl]-5-methyl-4-oxo-2,3-dihydro-1,5-benzoxazepin-3-yl]-1H-1,2,4-triazole-3-carboxamide | IC50 | 11 nM | US-10815206: RIP1 inhibitory compounds and methods for making and using the same |
| [3-(3,5-difluorophenyl)-3,4-dihydropyrazol-2-yl]-[3-[(4-fluoroindazol-2-yl)methyl]-1-bicyclo[1.1.1]pentanyl]methanone | IC50 | 11 nM | US-20250214942: INHIBITORS OF RECEPTOR INTERACTING PROTEIN KINASE I FOR THE TREATMENT OF DISEASE |
| (3-((1H-pyrazolo[4,3-b]- pyridin-1-yl)methyl)bicyclo- [1.1.1]pentan-1-yl)(5-(3,5- difluorophenyl)-4,5-dihydro- 1H-pyrazol-1-yl)methanone | IC50 | 11 nM | US-20250214942: INHIBITORS OF RECEPTOR INTERACTING PROTEIN KINASE I FOR THE TREATMENT OF DISEASE |
| (3-((4-fluoro-1H-indazol-1- yl)methyl)bicyclo[1.1.1]- pentan-1-yl)(5-phenyl-4,5- dihydro-1H-pyrazol-1-yl)- methanone | IC50 | 11 nM | US-20250214942: INHIBITORS OF RECEPTOR INTERACTING PROTEIN KINASE I FOR THE TREATMENT OF DISEASE |
| 3-(1-(3-((4-fluoro-1H- indazol-1-yl)methyl)bicyclo- [1.1.1]pentane-1-carbonyl)- 4,5-dihydro-1H-pyrazol-5- yl)benzonitrile | IC50 | 11 nM | US-20250214942: INHIBITORS OF RECEPTOR INTERACTING PROTEIN KINASE I FOR THE TREATMENT OF DISEASE |
| 1-((3-(5-(3,5-difluorophenyl)- 4,5-dihydro-1H-pyrazole-1- carbonyl)bicyclo[1.1.1]pentan- 1-yl)methyl)-1H-pyrrolo[2,3- b]pyridine-5-carbonitrile | IC50 | 11 nM | US-20250214942: INHIBITORS OF RECEPTOR INTERACTING PROTEIN KINASE I FOR THE TREATMENT OF DISEASE |
| (3-((4-bromo-2-chloro- phenoxy)methyl)bicyclo- [1.1.1]pentan-1-yl)(5-(3,5- difluorophenyl)-4,5-dihydro- 1H-pyrazol-1-yl)methanone | IC50 | 11 nM | US-20250214942: INHIBITORS OF RECEPTOR INTERACTING PROTEIN KINASE I FOR THE TREATMENT OF DISEASE |
| [3-[(4-fluoroindazol-1-yl)methyl]-1-bicyclo[1.1.1]pentanyl]-[3-(5-fluoro-3-pyridinyl)-3,4-dihydropyrazol-2-yl]methanone | IC50 | 12 nM | US-20250214942: INHIBITORS OF RECEPTOR INTERACTING PROTEIN KINASE I FOR THE TREATMENT OF DISEASE |
| (3-((4-bromo-2-fluoro- phenoxy)methyl)bicyclo- [1.1.1]pentan-1-yl)(5-(3,5- difluorophenyl)-4,5-dihydro- 1H-pyrazol-1-yl)methanone | IC50 | 13 nM | US-20250214942: INHIBITORS OF RECEPTOR INTERACTING PROTEIN KINASE I FOR THE TREATMENT OF DISEASE |
| TC001262 | KI | 13.7 nM | US-10092529: Necrosis inhibitors |
| [4-fluoro-2-(3-fluorophenyl)pyrrolidin-1-yl]-[3-[(5-fluoroindazol-1-yl)methyl]-1-bicyclo[1.1.1]pentanyl]methanone | IC50 | 14 nM | US-20250214942: INHIBITORS OF RECEPTOR INTERACTING PROTEIN KINASE I FOR THE TREATMENT OF DISEASE |
| 5-benzyl-N-[(3S)-7-[3-(1H-indazol-5-ylamino)-3-oxopropyl]-5-methyl-4-oxo-2,3-dihydro-1,5-benzoxazepin-3-yl]-1H-1,2,4-triazole-3-carboxamide | IC50 | 15.7 nM | US-10815206: RIP1 inhibitory compounds and methods for making and using the same |
| 5-benzyl-N-[7-[3-(1H-indazol-5-ylamino)-3-oxopropyl]-5-methyl-4-oxo-2,3-dihydro-1,5-benzoxazepin-3-yl]-1H-1,2,4-triazole-3-carboxamide | IC50 | 15.7 nM | US-11407736: RIP1 inhibitory compounds and methods for making and using the same |
| 6-[[3-[3-(3,5-difluorophenyl)-3,4-dihydropyrazole-2-carbonyl]-1-bicyclo[1.1.1]pentanyl]methoxy]pyrimidine-4-carbonitrile | IC50 | 16 nM | US-20250214942: INHIBITORS OF RECEPTOR INTERACTING PROTEIN KINASE I FOR THE TREATMENT OF DISEASE |
| 1-[[3-[3-(6-methylpyrazin-2-yl)-3,4-dihydropyrazole-2-carbonyl]-1-bicyclo[1.1.1]pentanyl]methyl]indazole-5-carbonitrile | IC50 | 16 nM | US-20250214942: INHIBITORS OF RECEPTOR INTERACTING PROTEIN KINASE I FOR THE TREATMENT OF DISEASE |
| 1-((3-(5-(3,5-difluorophenyl)- 4,5-dihydro-1H-pyrazole-1- carbonyl)bicyclo[1.1.1]- pentan-1-yl)methyl)-1H- indazole-6-carbonitrile | IC50 | 16 nM | US-20250214942: INHIBITORS OF RECEPTOR INTERACTING PROTEIN KINASE I FOR THE TREATMENT OF DISEASE |
| (3-((4-fluoro-1H-indazol-1- yl)methyl)bicyclo[1.1.1]- pentan-1-yl)(4-fluoro-2-(3- fluorophenyl)pyrrolidin-1- yl)methanone | IC50 | 16 nM | US-20250214942: INHIBITORS OF RECEPTOR INTERACTING PROTEIN KINASE I FOR THE TREATMENT OF DISEASE |
| 1-((3-(5-(3-cyanophenyl)-4,5- dihydro-1H-pyrazole-1- carbonyl)bicyclo[1.1.1]- pentan-1-yl)methyl)-1H- indazole-5-carbonitrile | IC50 | 16 nM | US-20250214942: INHIBITORS OF RECEPTOR INTERACTING PROTEIN KINASE I FOR THE TREATMENT OF DISEASE |
| 4-((3-(5-(3,5-difluorophenyl)- 4,5-dihydro-1H-pyrazole-1- carbonyl)bicyclo[1.1.1]pentan- 1-yl)methoxy)-3-fluoro- benzonitrile | IC50 | 16 nM | US-20250214942: INHIBITORS OF RECEPTOR INTERACTING PROTEIN KINASE I FOR THE TREATMENT OF DISEASE |
| [3-(3,5-difluorophenyl)-3,4-dihydropyrazol-2-yl]-[3-(fluoromethyl)-1-bicyclo[1.1.1]pentanyl]methanone | IC50 | 17 nM | US-20250214942: INHIBITORS OF RECEPTOR INTERACTING PROTEIN KINASE I FOR THE TREATMENT OF DISEASE |
| 1-((3-(5-(5-fluoropyridin-3- yl)-4,5-dihydro-1H-pyrazole- 1-carbonyl)bicyclo[1.1.1]- pentan-1-yl)methyl)-1H- indazole-5-carbonitrile | IC50 | 17 nM | US-20250214942: INHIBITORS OF RECEPTOR INTERACTING PROTEIN KINASE I FOR THE TREATMENT OF DISEASE |
| (5R)-5-[(7-chloro-1H-indol-3-yl)methyl]-3-methyl-2,4-Imidazolidinedione, 11 | EC50 | 18 nM | |
| (5-(3,5-difluorophenyl)-4,5- dihydro-1H-pyrazol-1-yl)(3- ((5-fluoro-2H-benzo[d]- [1,2,3]triazol-2-yl)methyl)- bicyclo[1.1.1]pentan-1-yl)- methanone | IC50 | 18 nM | US-20250214942: INHIBITORS OF RECEPTOR INTERACTING PROTEIN KINASE I FOR THE TREATMENT OF DISEASE |
| (3-((1H-pyrazolo[3,4-b]- pyrazin-1-yl)methyl)- bicyclo[1.1.1]pentan-1-yl)(5- (3,5-difluorophenyl)-4,5- dihydro-1H-pyrazol-1- yl)methanone | IC50 | 18 nM | US-20250214942: INHIBITORS OF RECEPTOR INTERACTING PROTEIN KINASE I FOR THE TREATMENT OF DISEASE |
| (5-(3,5-difluorophenyl)-4,5- dihydro-1H-pyrazol-1-yl)(3- (((3,5-difluoropyridin-2-yl)- oxy)methyl)bicyclo[1.1.1]- pentan-1-yl)methanone | IC50 | 18 nM | US-20250214942: INHIBITORS OF RECEPTOR INTERACTING PROTEIN KINASE I FOR THE TREATMENT OF DISEASE |
| (3-((2-chloro-4-fluoro- phenoxy)methyl)bicyclo- [1.1.1]pentan-1-yl)(5-(3,5- difluorophenyl)-4,5-dihydro- 1H-pyrazol-1-yl)methanone | IC50 | 18 nM | US-20250214942: INHIBITORS OF RECEPTOR INTERACTING PROTEIN KINASE I FOR THE TREATMENT OF DISEASE |
| (3-((2,4-difluorophenoxy)- methyl)bicyclo[1.1.1]pentan-1- yl)(5-(3,5-difluorophenyl)-4,5- dihydro-1H-pyrazol-1- yl)methanone | IC50 | 18 nM | US-20250214942: INHIBITORS OF RECEPTOR INTERACTING PROTEIN KINASE I FOR THE TREATMENT OF DISEASE |
| 5-benzyl-N-[(3S)-7-(4-methoxy-3-oxobutyl)-5-methyl-4-oxo-2,3-dihydro-1,5-benzoxazepin-3-yl]-1H-1,2,4-triazole-3-carboxamide | IC50 | 19 nM | US-10815206: RIP1 inhibitory compounds and methods for making and using the same |
| US10815206, Compound I-64 | IC50 | 19 nM | US-10815206: RIP1 inhibitory compounds and methods for making and using the same |
| ethyl 3-[3-[(5-benzyl-1H-1,2,4-triazole-3-carbonyl)amino]-5-methyl-4-oxo-2,3-dihydro-1,5-benzoxazepin-7-yl]propanoate | IC50 | 19 nM | US-11407736: RIP1 inhibitory compounds and methods for making and using the same |
| 5-benzyl-N-(7-ethynyl-5-methyl-4-oxo-2,3-dihydro-1,5-benzoxazepin-3-yl)-1H-1,2,4-triazole-3-carboxamide | IC50 | 19 nM | US-11407736: RIP1 inhibitory compounds and methods for making and using the same |
| [3-(3,5-difluorophenyl)-3,4-dihydropyrazol-2-yl]-[3-[(5-fluoroindazol-2-yl)methyl]-1-bicyclo[1.1.1]pentanyl]methanone | IC50 | 19 nM | US-20250214942: INHIBITORS OF RECEPTOR INTERACTING PROTEIN KINASE I FOR THE TREATMENT OF DISEASE |
| 2-((3-(5-(3,5-difluorophenyl)- 4,5-dihydro-1H-pyrazole-1- carbonyl)bicyclo[1.1.1]- pentan-1-yl)methyl)-2H- indazole-6-carbonitrile | IC50 | 19 nM | US-20250214942: INHIBITORS OF RECEPTOR INTERACTING PROTEIN KINASE I FOR THE TREATMENT OF DISEASE |
| 1-((3-(5-(3,5-difluorophenyl)- 4,5-dihydro-1H-pyrazole-1- carbonyl)bicyclo[1.1.1]- pentan-1-yl)methyl)-1H- indazole-4-carbonitrile | IC50 | 19 nM | US-20250214942: INHIBITORS OF RECEPTOR INTERACTING PROTEIN KINASE I FOR THE TREATMENT OF DISEASE |
| (3-((2H-benzo[d][1,2,3]- triazol-2-yl)methyl)bicyclo- [1.1.1]pentan-1-yl)(5-(3,5- difluorophenyl)-4,5-dihydro- 1H-pyrazol-1-yl)methanone | IC50 | 19 nM | US-20250214942: INHIBITORS OF RECEPTOR INTERACTING PROTEIN KINASE I FOR THE TREATMENT OF DISEASE |
| 1-((3-(4-fluoro-2-(3-fluoro- phenyl)pyrrolidine-1- carbonyl)bicyclo[1.1.1]- pentan-1-yl)methyl)-1H- indazole-5-carbonitrile | IC50 | 19 nM | US-20250214942: INHIBITORS OF RECEPTOR INTERACTING PROTEIN KINASE I FOR THE TREATMENT OF DISEASE |
| 6-((3-(5-(3,5-difluorophenyl)- 4,5-dihydro-1H-pyrazole-1- carbonyl)bicyclo[1.1.1]pentan- 1-yl)methoxy)nicotinonitrile | IC50 | 19 nM | US-20250214942: INHIBITORS OF RECEPTOR INTERACTING PROTEIN KINASE I FOR THE TREATMENT OF DISEASE |
| (3-((2-chloro-3-fluoro- phenoxy)methyl)bicyclo- [1.1.1]pentan-1-yl)(5-(3,5- difluorophenyl)-4,5-dihydro- 1H-pyrazol-1-yl)methanone | IC50 | 19 nM | US-20250214942: INHIBITORS OF RECEPTOR INTERACTING PROTEIN KINASE I FOR THE TREATMENT OF DISEASE |
| TC001207 | KI | 19.8 nM | US-10092529: Necrosis inhibitors |
| [3-(chloromethyl)-1-bicyclo[1.1.1]pentanyl]-[3-(3,5-difluorophenyl)-3,4-dihydropyrazol-2-yl]methanone | IC50 | 20 nM | US-20250214942: INHIBITORS OF RECEPTOR INTERACTING PROTEIN KINASE I FOR THE TREATMENT OF DISEASE |
| (3-((7-chloro-1H-pyrazolo- [4,3-c]pyridin-1-yl)methyl)- bicyclo[1.1.1]pentan-1-yl)(5- (3,5-difluorophenyl)-4,5- dihydro-1H-pyrazol-1- yl)methanone | IC50 | 20 nM | US-20250214942: INHIBITORS OF RECEPTOR INTERACTING PROTEIN KINASE I FOR THE TREATMENT OF DISEASE |
| (5-(3,5-difluorophenyl)-4,5- dihydro-1H-pyrazol-1-yl)(3- ((5-fluoro-1H-indol-1-yl)- methyl)bicyclo[1.1.1]pentan- 1-yl)methanone | IC50 | 20 nM | US-20250214942: INHIBITORS OF RECEPTOR INTERACTING PROTEIN KINASE I FOR THE TREATMENT OF DISEASE |
ChEMBL bioactivities
4555 potent at pChembl≥5 of 5316 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).
| pChembl | Type | Value | Unit | Molecule |
|---|---|---|---|---|
| 11.00 | IC50 | 0.01 | nM | CHEMBL6193201 |
| 11.00 | IC50 | 0.01 | nM | CHEMBL6191419 |
| 11.00 | IC50 | 0.01 | nM | CHEMBL6192383 |
| 10.30 | IC50 | 0.05 | nM | CHEMBL4067372 |
| 10.20 | IC50 | 0.063 | nM | CHEMBL3785745 |
| 10.10 | IC50 | 0.079 | nM | CHEMBL4093220 |
| 9.70 | IC50 | 0.2 | nM | CHEMBL3786997 |
| 9.55 | Kd | 0.28 | nM | CHEMBL5177284 |
| 9.52 | IC50 | 0.3 | nM | CHEMBL4439913 |
| 9.52 | Ki | 0.3 | nM | CHEMBL5885803 |
| 9.52 | IC50 | 0.3 | nM | CHEMBL6177790 |
| 9.49 | IC50 | 0.32 | nM | CHEMBL4068954 |
| 9.49 | IC50 | 0.32 | nM | CHEMBL4096224 |
| 9.40 | IC50 | 0.4 | nM | CHEMBL3785482 |
| 9.40 | IC50 | 0.4 | nM | CHEMBL4069318 |
| 9.40 | IC50 | 0.4 | nM | CHEMBL4060644 |
| 9.40 | IC50 | 0.4 | nM | GSK2982772 |
| 9.40 | IC50 | 0.4 | nM | CHEMBL4452233 |
| 9.40 | IC50 | 0.4 | nM | CHEMBL6165847 |
| 9.39 | Ki | 0.4074 | nM | CHEMBL4075976 |
| 9.37 | Ki | 0.43 | nM | TP-030-2 |
| 9.30 | IC50 | 0.5 | nM | CHEMBL4089558 |
| 9.30 | IC50 | 0.5 | nM | CHEMBL4099004 |
| 9.30 | IC50 | 0.5 | nM | GSK2982772 |
| 9.30 | IC50 | 0.5 | nM | CHEMBL4452233 |
| 9.30 | IC50 | 0.5 | nM | CHEMBL4537171 |
| 9.30 | EC50 | 0.5 | nM | CHEMBL5093571 |
| 9.22 | IC50 | 0.6 | nM | CHEMBL6175053 |
| 9.22 | IC50 | 0.6 | nM | CHEMBL6176716 |
| 9.20 | IC50 | 0.63 | nM | CHEMBL4081685 |
| 9.20 | IC50 | 0.63 | nM | CHEMBL4065561 |
| 9.15 | IC50 | 0.7 | nM | CHEMBL6177473 |
| 9.10 | Ki | 0.8 | nM | CHEMBL3785703 |
| 9.10 | IC50 | 0.79 | nM | CHEMBL3786078 |
| 9.10 | IC50 | 0.79 | nM | CHEMBL4088857 |
| 9.10 | IC50 | 0.8 | nM | CHEMBL6177790 |
| 9.07 | Ki | 0.8511 | nM | CHEMBL4061975 |
| 9.05 | IC50 | 0.9 | nM | CHEMBL4439913 |
| 9.05 | IC50 | 0.9 | nM | CHEMBL6163751 |
| 9.05 | IC50 | 0.9 | nM | CHEMBL6173421 |
| 9.04 | Ki | 0.912 | nM | CHEMBL4100398 |
| 9.04 | Ki | 0.912 | nM | CHEMBL4069537 |
| 9.04 | Ki | 0.91 | nM | CHEMBL6145720 |
| 9.03 | IC50 | 0.94 | nM | CHEMBL3785745 |
| 9.01 | Ki | 0.9772 | nM | GSK2982772 |
| 9.00 | IC50 | 1 | nM | GSK2982772 |
| 9.00 | IC50 | 1 | nM | CHEMBL4099698 |
| 9.00 | IC50 | 1 | nM | CHEMBL4080978 |
| 9.00 | IC50 | 1 | nM | CHEMBL4067372 |
| 9.00 | IC50 | 1 | nM | CHEMBL4514271 |
PubChem BioAssay actives
974 with measured affinity, of 1891 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 |
|---|---|---|---|---|
| 2-benzyl-N-[(3S)-5-methyl-4-oxo-2,3-dihydro-1,5-benzoxazepin-3-yl]tetrazole-5-carboxamide | 1432226: Inhibition of human RIP1 (1 to 375 residues) expressed in baculovirus infected insect cells preincubated for 1 hr followed by ATP addition measured after 5 hrs by ADP-Glo luminescence assay | ic50 | 0.0001 | uM |
| 5-benzyl-N-[(3S)-5-methyl-4-oxo-2,3-dihydro-1,5-benzoxazepin-3-yl]-1,3-oxazole-2-carboxamide | 1432226: Inhibition of human RIP1 (1 to 375 residues) expressed in baculovirus infected insect cells preincubated for 1 hr followed by ATP addition measured after 5 hrs by ADP-Glo luminescence assay | ic50 | 0.0001 | uM |
| 5-benzyl-N-[(3R)-5-methyl-4-oxo-2,3-dihydro-1,5-benzothiazepin-3-yl]-1,2-oxazole-3-carboxamide | 1432226: Inhibition of human RIP1 (1 to 375 residues) expressed in baculovirus infected insect cells preincubated for 1 hr followed by ATP addition measured after 5 hrs by ADP-Glo luminescence assay | ic50 | 0.0001 | uM |
| 5-benzyl-N-[(3S)-1-methyl-2-oxo-4,5-dihydro-3H-1-benzazepin-3-yl]-1,2-oxazole-3-carboxamide | 1290032: Inhibition of Flag-tagged human RIP1 (1 to 324 residues) after 30 mins by ADP-Glo reagent based assay | ic50 | 0.0002 | uM |
| methyl N-[(3S)-3-[(5-benzyl-1,2-oxazole-3-carbonyl)amino]-5-methyl-4-oxo-2,3-dihydro-1,5-benzoxazepin-7-yl]carbamate | 1432226: Inhibition of human RIP1 (1 to 375 residues) expressed in baculovirus infected insect cells preincubated for 1 hr followed by ATP addition measured after 5 hrs by ADP-Glo luminescence assay | ic50 | 0.0003 | uM |
| tert-butyl 2-[4-[5-(methylcarbamoyl)benzimidazol-1-yl]phenyl]acetate | 1580388: Inhibition of human RIPK1 by ADP-Glo assay | ic50 | 0.0003 | uM |
| 7-(4-aminocyclohexyl)-5-(2-fluoro-4-methylphenyl)pyrrolo[2,3-d]pyrimidin-4-amine | 1880918: Binding affinity to human RIPK1 in human Jurkat cells | kd | 0.0003 | uM |
| N-[(3S)-7-acetamido-5-methyl-4-oxo-2,3-dihydro-1,5-benzoxazepin-3-yl]-5-benzyl-1,2-oxazole-3-carboxamide | 1432226: Inhibition of human RIP1 (1 to 375 residues) expressed in baculovirus infected insect cells preincubated for 1 hr followed by ATP addition measured after 5 hrs by ADP-Glo luminescence assay | ic50 | 0.0003 | uM |
| 5-benzyl-N-[(3S)-5-methyl-4-oxo-2,3-dihydro-1,5-benzoxazepin-3-yl]-1H-pyrazole-3-carboxamide | 1290032: Inhibition of Flag-tagged human RIP1 (1 to 324 residues) after 30 mins by ADP-Glo reagent based assay | ic50 | 0.0004 | uM |
| 1-benzyl-N-[(3S)-5-methyl-4-oxo-2,3-dihydro-1,5-benzoxazepin-3-yl]imidazole-4-carboxamide | 1432226: Inhibition of human RIP1 (1 to 375 residues) expressed in baculovirus infected insect cells preincubated for 1 hr followed by ATP addition measured after 5 hrs by ADP-Glo luminescence assay | ic50 | 0.0004 | uM |
| 5-benzyl-N-[(3S)-7,9-difluoro-2-oxo-1,3,4,5-tetrahydro-1-benzazepin-3-yl]-1H-1,2,4-triazole-3-carboxamide | 1509723: Inhibition of RIP1 in human neutrophils assessed as inhibition of TNF-alpha/QVD-Oph/RMT5265-stimulated MIP-1 beta cytokine overproduction measured at 21 hrs post stimulation by sandwich ELISA | ic50 | 0.0004 | uM |
| (3S)-3-(2-benzyl-3-chloro-7-oxo-4,5-dihydropyrazolo[3,4-c]pyridin-6-yl)-5-methyl-2,3-dihydro-1,5-benzoxazepin-4-one | 1469067: Inhibition of fluorescent-labeled 3-(3-((3-(4-amino-5-(4-(3-(2-fluoro-5-(trifluoromethyl)phenyl)ureido)-phenyl)-7H-pyrrolo[2,3-d]pyrimidin-7-yl)propyl)amino)-3-oxopropyl)-5,5-difluoro-7,9-dimethyl-5H-dipyrrolo[1,2-c:2’,1’-f]-[1,3,2]diazaborinin-4-ium-5-uide binding to human N-terminal GST/His-tagged RIPK1 (1 to 375 residues) expressed in baculovirus expression system by TR-FRET assay | ki | 0.0004 | uM |
| 5-benzyl-1-methyl-N-[(3S)-5-methyl-4-oxo-2,3-dihydro-1,5-benzoxazepin-3-yl]pyrazole-3-carboxamide | 1432226: Inhibition of human RIP1 (1 to 375 residues) expressed in baculovirus infected insect cells preincubated for 1 hr followed by ATP addition measured after 5 hrs by ADP-Glo luminescence assay | ic50 | 0.0004 | uM |
| 5-benzyl-N-[(3S)-5-methyl-4-oxo-2,3-dihydro-1,5-benzoxazepin-3-yl]-1H-1,2,4-triazole-3-carboxamide | 1432234: Inhibition of RIP1 in human primary neutrophils assessed as reduction in TNFalpha/QCD-OPh/SMAC mimetic RMT 5265-induced necroptosis at 21 hrs post-stimulation by LDH release assay | ic50 | 0.0004 | uM |
| 5-benzyl-N-[(3S)-5-methyl-4-oxo-7-(2-oxo-3H-1,3,4-oxadiazol-5-yl)-2,3-dihydro-1,5-benzoxazepin-3-yl]-1,2-oxazole-3-carboxamide | 1432226: Inhibition of human RIP1 (1 to 375 residues) expressed in baculovirus infected insect cells preincubated for 1 hr followed by ATP addition measured after 5 hrs by ADP-Glo luminescence assay | ic50 | 0.0005 | uM |
| 1-[3-(3-fluorophenyl)-3,4-dihydropyrazol-2-yl]-2,2-dimethylpropan-1-one | 1554569: Inhibition of human GST/His-tagged RIP1 (1 to 375 residues) expressed in baculovirus expression system assessed as reduction in autophosphorylation measured after 4 hrs in presence of ATP by ADP-Glo luminescence assay | ic50 | 0.0005 | uM |
| (3-phenoxyazetidin-1-yl)-[(3S)-3-phenyl-3,4-dihydropyrazol-2-yl]methanone | 1819797: Inhibition of recombinant N-terminal GST-tagged human RIPK1 (1 to 327 residues) expressed in baculovirus infected Sf9 insect cells preincubated for 40 mins followed by substrate addition and measured after 60 mins by ADP-glo luminescence assay | ec50 | 0.0005 | uM |
| 5-benzyl-N-[(3S)-5-methyl-4-oxo-2,3-dihydro-1,5-benzoxazepin-3-yl]-1,2,4-oxadiazole-3-carboxamide | 1432226: Inhibition of human RIP1 (1 to 375 residues) expressed in baculovirus infected insect cells preincubated for 1 hr followed by ATP addition measured after 5 hrs by ADP-Glo luminescence assay | ic50 | 0.0005 | uM |
| 1-benzyl-N-[(3S)-5-methyl-4-oxo-2,3-dihydro-1,5-benzoxazepin-3-yl]-1,2,4-triazole-3-carboxamide | 1432226: Inhibition of human RIP1 (1 to 375 residues) expressed in baculovirus infected insect cells preincubated for 1 hr followed by ATP addition measured after 5 hrs by ADP-Glo luminescence assay | ic50 | 0.0006 | uM |
| 5-benzyl-N-[(3S)-7-(methanesulfonamido)-5-methyl-4-oxo-2,3-dihydro-1,5-benzoxazepin-3-yl]-1,2-oxazole-3-carboxamide | 1432226: Inhibition of human RIP1 (1 to 375 residues) expressed in baculovirus infected insect cells preincubated for 1 hr followed by ATP addition measured after 5 hrs by ADP-Glo luminescence assay | ic50 | 0.0006 | uM |
| 5-benzyl-N-[(3S)-5-methyl-4-oxo-2,3-dihydro-1,5-benzoxazepin-3-yl]-1,3,4-oxadiazole-2-carboxamide | 1432226: Inhibition of human RIP1 (1 to 375 residues) expressed in baculovirus infected insect cells preincubated for 1 hr followed by ATP addition measured after 5 hrs by ADP-Glo luminescence assay | ic50 | 0.0008 | uM |
| 5-benzyl-N-[(3S)-5-methyl-4-oxo-2,3-dihydro-1H-1,5-benzodiazepin-3-yl]-1,2-oxazole-3-carboxamide | 1290023: Inhibition of human RIP1 (1 to 375 residues) after 4 hrs by ADP-Glo reagent based assay | ic50 | 0.0008 | uM |
| 5-benzyl-N-[(3S)-5-methyl-4-oxo-2,3-dihydro-1,5-benzoxazepin-3-yl]-1,2-oxazole-3-carboxamide | 1290029: Competitive inhibition of human RIP1 (1 to 375 residues) in presence of increasing ATP by ADP-Glo reagent based assay | ki | 0.0008 | uM |
| (3S)-3-(2-benzyl-3-chloro-7-oxo-4,5-dihydropyrazolo[3,4-c]pyridin-6-yl)-5-methyl-4-oxo-2,3-dihydro-1,5-benzoxazepine-8-carbonitrile | 1469067: Inhibition of fluorescent-labeled 3-(3-((3-(4-amino-5-(4-(3-(2-fluoro-5-(trifluoromethyl)phenyl)ureido)-phenyl)-7H-pyrrolo[2,3-d]pyrimidin-7-yl)propyl)amino)-3-oxopropyl)-5,5-difluoro-7,9-dimethyl-5H-dipyrrolo[1,2-c:2’,1’-f]-[1,3,2]diazaborinin-4-ium-5-uide binding to human N-terminal GST/His-tagged RIPK1 (1 to 375 residues) expressed in baculovirus expression system by TR-FRET assay | ki | 0.0009 | uM |
| (3S)-3-(2-benzyl-3-chloro-7-oxo-4,5-dihydropyrazolo[3,4-c]pyridin-6-yl)-N,5-dimethyl-4-oxo-2,3-dihydro-1,5-benzoxazepine-8-carboxamide | 1469067: Inhibition of fluorescent-labeled 3-(3-((3-(4-amino-5-(4-(3-(2-fluoro-5-(trifluoromethyl)phenyl)ureido)-phenyl)-7H-pyrrolo[2,3-d]pyrimidin-7-yl)propyl)amino)-3-oxopropyl)-5,5-difluoro-7,9-dimethyl-5H-dipyrrolo[1,2-c:2’,1’-f]-[1,3,2]diazaborinin-4-ium-5-uide binding to human N-terminal GST/His-tagged RIPK1 (1 to 375 residues) expressed in baculovirus expression system by TR-FRET assay | ki | 0.0009 | uM |
| (3S)-3-(2-benzyl-3-chloro-7-oxo-4,5-dihydropyrazolo[3,4-c]pyridin-6-yl)-5-methyl-4-oxo-2,3-dihydro-1,5-benzoxazepine-7-carbonitrile | 1469067: Inhibition of fluorescent-labeled 3-(3-((3-(4-amino-5-(4-(3-(2-fluoro-5-(trifluoromethyl)phenyl)ureido)-phenyl)-7H-pyrrolo[2,3-d]pyrimidin-7-yl)propyl)amino)-3-oxopropyl)-5,5-difluoro-7,9-dimethyl-5H-dipyrrolo[1,2-c:2’,1’-f]-[1,3,2]diazaborinin-4-ium-5-uide binding to human N-terminal GST/His-tagged RIPK1 (1 to 375 residues) expressed in baculovirus expression system by TR-FRET assay | ki | 0.0009 | uM |
| 1-benzyl-N-[(3S)-5-methyl-4-oxo-2,3-dihydro-1,5-benzoxazepin-3-yl]triazole-4-carboxamide | 1432226: Inhibition of human RIP1 (1 to 375 residues) expressed in baculovirus infected insect cells preincubated for 1 hr followed by ATP addition measured after 5 hrs by ADP-Glo luminescence assay | ic50 | 0.0010 | uM |
| 5-benzyl-N-[(3S)-5-methyl-4-oxo-7-(1H-pyrazol-5-yl)-2,3-dihydro-1,5-benzoxazepin-3-yl]-1,2-oxazole-3-carboxamide | 1432226: Inhibition of human RIP1 (1 to 375 residues) expressed in baculovirus infected insect cells preincubated for 1 hr followed by ATP addition measured after 5 hrs by ADP-Glo luminescence assay | ic50 | 0.0010 | uM |
| 6-[4-[(3S)-3-(3,5-difluorophenyl)-3,4-dihydropyrazole-2-carbonyl]piperidin-1-yl]pyrimidine-4-carbonitrile | 1554569: Inhibition of human GST/His-tagged RIP1 (1 to 375 residues) expressed in baculovirus expression system assessed as reduction in autophosphorylation measured after 4 hrs in presence of ATP by ADP-Glo luminescence assay | ic50 | 0.0010 | uM |
| (3S)-3-[2-[(2,6-difluorophenyl)methyl]-7-oxo-4,5-dihydropyrazolo[3,4-c]pyridin-6-yl]-5-methyl-2,3-dihydro-1,5-benzoxazepin-4-one | 1469067: Inhibition of fluorescent-labeled 3-(3-((3-(4-amino-5-(4-(3-(2-fluoro-5-(trifluoromethyl)phenyl)ureido)-phenyl)-7H-pyrrolo[2,3-d]pyrimidin-7-yl)propyl)amino)-3-oxopropyl)-5,5-difluoro-7,9-dimethyl-5H-dipyrrolo[1,2-c:2’,1’-f]-[1,3,2]diazaborinin-4-ium-5-uide binding to human N-terminal GST/His-tagged RIPK1 (1 to 375 residues) expressed in baculovirus expression system by TR-FRET assay | ki | 0.0011 | uM |
| 2-benzyl-6-[(3S)-5-methyl-4-oxo-2,3-dihydro-1,5-benzoxazepin-3-yl]-7-oxo-4,5-dihydropyrazolo[3,4-c]pyridine-3-carbonitrile | 1469067: Inhibition of fluorescent-labeled 3-(3-((3-(4-amino-5-(4-(3-(2-fluoro-5-(trifluoromethyl)phenyl)ureido)-phenyl)-7H-pyrrolo[2,3-d]pyrimidin-7-yl)propyl)amino)-3-oxopropyl)-5,5-difluoro-7,9-dimethyl-5H-dipyrrolo[1,2-c:2’,1’-f]-[1,3,2]diazaborinin-4-ium-5-uide binding to human N-terminal GST/His-tagged RIPK1 (1 to 375 residues) expressed in baculovirus expression system by TR-FRET assay | ki | 0.0011 | uM |
| N-(6-propan-2-ylsulfonylquinolin-4-yl)-1,3-benzothiazol-6-amine | 1580388: Inhibition of human RIPK1 by ADP-Glo assay | ic50 | 0.0013 | uM |
| 1-[3-(3,5-difluorophenyl)-3,4-dihydropyrazol-2-yl]-2,2-dimethylpropan-1-one | 1554569: Inhibition of human GST/His-tagged RIP1 (1 to 375 residues) expressed in baculovirus expression system assessed as reduction in autophosphorylation measured after 4 hrs in presence of ATP by ADP-Glo luminescence assay | ic50 | 0.0013 | uM |
| 1-[3-[5-(3-aminophenyl)-1H-pyrrolo[2,3-b]pyridin-3-yl]phenyl]-3-[2-fluoro-5-(trifluoromethyl)phenyl]urea | 1065034: Displacement of (14-(2-{[3-({2-{[4-(cyanomethyl)phenyl]amino}-6-[(5-cyclopropyl-1H-pyrazol-3-yl)amino]-4-pyrimidinyl}amino)propyl]amino}-2-oxoethyl)-16,16,18,18-tetramethyl-6,7,7a,8a,9,10,16,18-octahydrobenzo[2’’,3’’]indolizino[8’’,7’’:5’,6’]pyrano[3’,2’:3,4]pyrido[1,2-a]indol-5-ium-2-sulfonate from human N-terminal His-GST-TEV-fused RIP1 kinase domain (1 to 375) expressed in baculovirus infected insect Sf9 cells preincubated for 10 mins followed by fluorescent ligand addition measured after 15 mins by fluorescence polarization assay | ic50 | 0.0013 | uM |
| 1-[3-(3-fluoro-4-methylphenyl)-3,4-dihydropyrazol-2-yl]-2,2-dimethylpropan-1-one | 2127037: Binding affinity to recombinant RIPK1 (unknown origin) assessed as dissociation constant by KINOMEscan assay | kd | 0.0016 | uM |
| 2,2-dimethyl-1-[(3S)-3-phenyl-3,4-dihydropyrazol-2-yl]propan-1-one | 1554569: Inhibition of human GST/His-tagged RIP1 (1 to 375 residues) expressed in baculovirus expression system assessed as reduction in autophosphorylation measured after 4 hrs in presence of ATP by ADP-Glo luminescence assay | ic50 | 0.0016 | uM |
| [(3S)-3-phenyl-3,4-dihydropyrazol-2-yl]-(1-pyrimidin-2-ylpiperidin-4-yl)methanone | 1554569: Inhibition of human GST/His-tagged RIP1 (1 to 375 residues) expressed in baculovirus expression system assessed as reduction in autophosphorylation measured after 4 hrs in presence of ATP by ADP-Glo luminescence assay | ic50 | 0.0016 | uM |
| cyclohexyl-(3-phenyl-3,4-dihydropyrazol-2-yl)methanone | 1554569: Inhibition of human GST/His-tagged RIP1 (1 to 375 residues) expressed in baculovirus expression system assessed as reduction in autophosphorylation measured after 4 hrs in presence of ATP by ADP-Glo luminescence assay | ic50 | 0.0016 | uM |
| (3S)-3-[2-[(2-fluorophenyl)methyl]-7-oxo-4,5-dihydropyrazolo[3,4-c]pyridin-6-yl]-5-methyl-2,3-dihydro-1,5-benzoxazepin-4-one | 1469067: Inhibition of fluorescent-labeled 3-(3-((3-(4-amino-5-(4-(3-(2-fluoro-5-(trifluoromethyl)phenyl)ureido)-phenyl)-7H-pyrrolo[2,3-d]pyrimidin-7-yl)propyl)amino)-3-oxopropyl)-5,5-difluoro-7,9-dimethyl-5H-dipyrrolo[1,2-c:2’,1’-f]-[1,3,2]diazaborinin-4-ium-5-uide binding to human N-terminal GST/His-tagged RIPK1 (1 to 375 residues) expressed in baculovirus expression system by TR-FRET assay | ki | 0.0017 | uM |
| (3S)-3-[2-[(2,6-difluorophenyl)methyl]-7-oxo-4,5-dihydropyrazolo[3,4-c]pyridin-6-yl]-5-methyl-4-oxo-2,3-dihydro-1,5-benzoxazepine-8-carbonitrile | 1469067: Inhibition of fluorescent-labeled 3-(3-((3-(4-amino-5-(4-(3-(2-fluoro-5-(trifluoromethyl)phenyl)ureido)-phenyl)-7H-pyrrolo[2,3-d]pyrimidin-7-yl)propyl)amino)-3-oxopropyl)-5,5-difluoro-7,9-dimethyl-5H-dipyrrolo[1,2-c:2’,1’-f]-[1,3,2]diazaborinin-4-ium-5-uide binding to human N-terminal GST/His-tagged RIPK1 (1 to 375 residues) expressed in baculovirus expression system by TR-FRET assay | ki | 0.0018 | uM |
| N-(5-benzyl-1,3-thiazol-2-yl)-1-methyl-2-oxo-4,5-dihydro-3H-1-benzazepine-3-carboxamide | 2139608: Inhibition of human RIPK1 assessed as inhibition constant by ADP-Glo Kinase assay | ki | 0.0019 | uM |
| 1-[4-(4-aminofuro[2,3-d]pyrimidin-5-yl)phenyl]-3-[2-fluoro-5-(trifluoromethyl)phenyl]urea | 1469067: Inhibition of fluorescent-labeled 3-(3-((3-(4-amino-5-(4-(3-(2-fluoro-5-(trifluoromethyl)phenyl)ureido)-phenyl)-7H-pyrrolo[2,3-d]pyrimidin-7-yl)propyl)amino)-3-oxopropyl)-5,5-difluoro-7,9-dimethyl-5H-dipyrrolo[1,2-c:2’,1’-f]-[1,3,2]diazaborinin-4-ium-5-uide binding to human N-terminal GST/His-tagged RIPK1 (1 to 375 residues) expressed in baculovirus expression system by TR-FRET assay | ki | 0.0020 | uM |
| 4-[4-[(3S)-3-(3,5-difluorophenyl)-3,4-dihydropyrazole-2-carbonyl]piperidin-1-yl]pyrimidine-2-carbonitrile | 1554570: Inhibition of RIP1 in human U937 cells assessed as reduction in TNFalpha/QVD-Oph-induced necroptosis measured after 24 hrs by cell titer-glo luminescent cell viability assay | ic50 | 0.0020 | uM |
| 5-[4-[(3S)-3-(3,5-difluorophenyl)-3,4-dihydropyrazole-2-carbonyl]piperidin-1-yl]pyrazine-2-carbonitrile | 1554569: Inhibition of human GST/His-tagged RIP1 (1 to 375 residues) expressed in baculovirus expression system assessed as reduction in autophosphorylation measured after 4 hrs in presence of ATP by ADP-Glo luminescence assay | ic50 | 0.0020 | uM |
| 4-benzyl-N-[(3S)-5-methyl-4-oxo-2,3-dihydro-1,5-benzoxazepin-3-yl]pyridine-2-carboxamide | 1432226: Inhibition of human RIP1 (1 to 375 residues) expressed in baculovirus infected insect cells preincubated for 1 hr followed by ATP addition measured after 5 hrs by ADP-Glo luminescence assay | ic50 | 0.0020 | uM |
| (3-phenyl-3,4-dihydropyrazol-2-yl)-[1-(pyridine-2-carbonyl)piperidin-4-yl]methanone | 1554569: Inhibition of human GST/His-tagged RIP1 (1 to 375 residues) expressed in baculovirus expression system assessed as reduction in autophosphorylation measured after 4 hrs in presence of ATP by ADP-Glo luminescence assay | ic50 | 0.0025 | uM |
| [(3S)-3-phenyl-3,4-dihydropyrazol-2-yl]-(1-pyridin-2-ylpiperidin-4-yl)methanone | 1554569: Inhibition of human GST/His-tagged RIP1 (1 to 375 residues) expressed in baculovirus expression system assessed as reduction in autophosphorylation measured after 4 hrs in presence of ATP by ADP-Glo luminescence assay | ic50 | 0.0025 | uM |
| 2-benzyl-6-[(3S)-5-methyl-4-oxo-2,3-dihydro-1,5-benzoxazepin-3-yl]-7-oxo-4,5-dihydropyrazolo[3,4-c]pyridine-3-carboxamide | 1469067: Inhibition of fluorescent-labeled 3-(3-((3-(4-amino-5-(4-(3-(2-fluoro-5-(trifluoromethyl)phenyl)ureido)-phenyl)-7H-pyrrolo[2,3-d]pyrimidin-7-yl)propyl)amino)-3-oxopropyl)-5,5-difluoro-7,9-dimethyl-5H-dipyrrolo[1,2-c:2’,1’-f]-[1,3,2]diazaborinin-4-ium-5-uide binding to human N-terminal GST/His-tagged RIPK1 (1 to 375 residues) expressed in baculovirus expression system by TR-FRET assay | ki | 0.0025 | uM |
| 5-benzyl-N-[(3S)-6,8-difluoro-5-methyl-4-oxo-2,3-dihydro-1,5-benzoxazepin-3-yl]-1H-1,2,4-triazole-3-carboxamide | 1532932: Binding affinity to RIP1 (unknown origin) by fluorescence polarization assay | ic50 | 0.0025 | uM |
| [1-(1,3-oxazole-5-carbonyl)piperidin-4-yl]-[(3S)-3-phenyl-3,4-dihydropyrazol-2-yl]methanone | 1554569: Inhibition of human GST/His-tagged RIP1 (1 to 375 residues) expressed in baculovirus expression system assessed as reduction in autophosphorylation measured after 4 hrs in presence of ATP by ADP-Glo luminescence assay | ic50 | 0.0025 | uM |
CTD chemical–gene interactions
115 total (human), top 30 by PubMed support.
| Chemical | Actions (top 5) | PubMed papers |
|---|---|---|
| necrostatin-1 | increases reaction, increases phosphorylation, affects binding, affects cotreatment, affects reaction (+2 more) | 7 |
| bisphenol A | decreases reaction, increases expression, increases reaction, increases methylation | 3 |
| benzyloxycarbonyl-valyl-alanyl-aspartic acid | affects cotreatment, affects localization, decreases reaction, increases expression, increases reaction | 3 |
| Arsenic Trioxide | increases expression, decreases expression, increases cleavage | 3 |
| Cadmium | affects binding, increases abundance, increases expression, increases phosphorylation, affects reaction (+4 more) | 3 |
| moringin | affects cotreatment, decreases expression | 2 |
| 2,2’,4,4’-tetrabromodiphenyl ether | decreases expression, affects cotreatment, affects reaction, decreases reaction | 2 |
| Resveratrol | affects cotreatment, increases expression, decreases reaction | 2 |
| Acetylcysteine | decreases reaction, increases expression, increases reaction | 2 |
| Ethanol | affects binding, increases reaction, increases expression, decreases reaction | 2 |
| Benzo(a)pyrene | increases expression, increases methylation | 2 |
| Cannabidiol | decreases expression, increases expression, affects cotreatment | 2 |
| Plant Extracts | affects cotreatment, increases expression, decreases reaction | 2 |
| 3-((6-(2-methoxyphenyl)pyrimidin-4-yl)amino)phenyl)methane sulfonamide | decreases expression | 1 |
| 1-hydroxyalantolactone | decreases reaction, increases ubiquitination | 1 |
| CBLC137 | increases expression | 1 |
| GSK872 | affects cotreatment, affects reaction, decreases expression, decreases reaction | 1 |
| dihydrotanshinone I | increases phosphorylation, decreases reaction | 1 |
| 3-monochloropropane-1, 2 diol ester | increases expression, decreases reaction | 1 |
| dimethoxon | decreases expression | 1 |
| 2-anisidine | increases expression | 1 |
| propylparaben | increases expression | 1 |
| beta-lapachone | increases expression | 1 |
| methamidophos | decreases expression | 1 |
| sodium arsenite | increases expression | 1 |
| acacetin | increases expression | 1 |
| sodium sulfite | increases expression | 1 |
| ochratoxin A | decreases expression | 1 |
| palmitoyl glycerol | decreases expression | 1 |
| ferrous chloride | decreases expression | 1 |
ChEMBL screening assays
400 unique, capped per target: 391 binding, 7 admet, 2 functional
Representative assays (with source publication via chembl_document):
| Assay ID | Type | Description | Source paper |
|---|---|---|---|
| CHEMBL2416956 | Binding | Ratio of necrostatin-21 EC50 to compound EC50 for RIP1/JNK2 (unknown origin)-mediated necrosis | A novel necroptosis inhibitor-necrostatin-21 and its SAR study. — Bioorg Med Chem Lett |
| CHEMBL4344882 | ADMET | Displacement of fluorescein labeled probe from full length human GST-tagged RIPK1 expressed in Sf9 cells incubated for 60 mins by HTRF assay | Identification of RIPK3 Type II Inhibitors Using High-Throughput Mechanistic Studies in Hit Triage. — ACS Med Chem Lett |
| CHEMBL5210011 | Functional | Affinity Phenotypic Cellular interaction (CytoTox 96 nonradioactive cytotoxicity assay (necroptosis in HT29 cells; Promega)) EUB0000719a RIPK1 | Affinity Phenotypic Cellular Literature for EUbOPEN Chemogenomics Library wave 3 |
Cellosaurus cell lines
10 cell lines: 9 cancer cell line, 1 transformed cell line
First 10 cell lines (id-ordered, not curated):
| Cellosaurus | Name | Category | Sex |
|---|---|---|---|
| CVCL_B1AJ | Abcam THP-1 RIPK1 KO | Cancer cell line | Male |
| CVCL_D7ZF | Ubigene A-549 RIPK1 KO | Cancer cell line | Male |
| CVCL_D8UM | Ubigene HCT 116 RIPK1 KO | Cancer cell line | Male |
| CVCL_D9QJ | Ubigene HEK293 RIPK1 KO | Transformed cell line | Female |
| CVCL_D9WE | Ubigene HT-1080 RIPK1 KO | Cancer cell line | Male |
| CVCL_E0MS | Ubigene HeLa RIPK1 KO | Cancer cell line | Female |
| CVCL_E0YP | Ubigene MDA-MB-231 RIPK1 KO | Cancer cell line | Female |
| CVCL_E1CB | Ubigene SK-OV-3 RIPK1 KO | Cancer cell line | Female |
| CVCL_TJ10 | HAP1 RIPK1 (-) 1 | Cancer cell line | Male |
| CVCL_TJ11 | HAP1 RIPK1 (-) 2 | Cancer cell line | Male |
Clinical trials (associated diseases)
99 trials via MONDO — disease-level, not drug-specific.
| Trial | Phase | Status | Title |
|---|---|---|---|
| NCT03677557 | PHASE4 | UNKNOWN | Safety, Tolerability, Patient Satisfaction and Cost of 16.5% Subcutaneous Immunoglobulin (Cutaquig®) Treatment |
| NCT02562170 | PHASE4 | COMPLETED | Protexa® Versus TiLoopBra® in Immediate Breast Reconstruction- A Pilot Study |
| NCT00001646 | PHASE3 | COMPLETED | Voriconazole vs. Amphotericin B in the Treatment of Invasive Aspergillosis |
| NCT00220766 | PHASE3 | COMPLETED | Rapid Infusion of Immune Globulin Intravenous (Human) In Primary Immunodeficiency Patients |
| NCT00468273 | PHASE3 | COMPLETED | A Clinical Study of Intravenous Immunoglobulin |
| NCT00811174 | PHASE3 | TERMINATED | Efficacy, Safety and Kinetics Study of Octagam 10% in Primary Immunodeficiency Diseases |
| NCT01012323 | PHASE3 | COMPLETED | A Study of NewGam, Human Immunoglobulin 10%, in Patients With Primary Immunodeficiency Diseases |
| NCT01313507 | PHASE3 | COMPLETED | High Infusion Rate Study of Immunoglobulin Intravenous (Human) 10% (NewGam) |
| NCT01406470 | PHASE3 | COMPLETED | Phase 3 Study of Immune Globulin Intravenous (Human)IVIG-SN™ in Subjects With Primary Immunodeficiency |
| NCT02783482 | PHASE3 | COMPLETED | Study of Immune Globulin Intravenous (Human) GC5107 in Subjects With Primary Humoral Immunodeficiency |
| NCT02810444 | PHASE3 | COMPLETED | Study to Investigate Efficacy, Safety and Pharmacokinetics of BT595 in Subjects With PID |
| NCT03961009 | PHASE3 | COMPLETED | Clinical Assessment of Pharmacokinetics, Efficacy, and Safety of 10% IVIg in PID Patients |
| NCT04842643 | PHASE3 | COMPLETED | An Extension Study of TAK-664 for Japanese People With Primary Immunodeficiency Disease |
| NCT04944979 | PHASE3 | ACTIVE_NOT_RECRUITING | Clinical Assessment of Pharmacokinetics, Efficacy, and Safety of 10% IVIg in Pediatric PID Patients (KIDCARES10) |
| NCT06089122 | PHASE3 | UNKNOWN | Efficacy, Safety, and Pharmacokinetics of Shu Yang IVIG |
| NCT06150833 | PHASE3 | UNKNOWN | Efficacy and Safety and Pharmacokinetics of Boya IVIG |
| NCT07346859 | PHASE3 | RECRUITING | Study of BP-SCIG 20% in Patients With Primary Immunodeficiency (PID) |
| NCT00673335 | PHASE3 | COMPLETED | Letrozole in Preventing Breast Cancer in Postmenopausal Women With a BRCA1 or BRCA2 Mutation |
| NCT00685256 | PHASE3 | COMPLETED | Standard Genetic Counseling With or Without a Decision Guide in Improving Communication Between Mothers Undergoing BRCA1/2 Testing and Their Minor-Age Children |
| NCT03162276 | PHASE3 | UNKNOWN | Trial of Inquiry Based Stress Reduction (IBSR) Program for BRCA1/2 Mutation Carriers |
| NCT00001438 | PHASE2 | COMPLETED | A Pilot Study of the Combination of Retinoic Acid and Interferon-Alpha2a for the Treatment of Lymphoproliferative Disorders in Children With Immunodeficiency Syndromes |
| NCT00176865 | PHASE2 | COMPLETED | Stem Cell Transplant for Immunologic or Histiocytic Disorders |
| NCT00389324 | PHASE2 | COMPLETED | A Trial of the Pharmacokinetics, Safety, and Tolerability of Subcutaneous Gamunex® in Primary Immunodeficiency |
| NCT00598481 | PHASE2 | COMPLETED | ADA Gene Transfer Into Hematopoietic Stem/Progenitor Cells for the Treatment of ADA-SCID |
| NCT01856582 | PHASE2 | TERMINATED | CD34+ Stem Cell Infusion to Augment Graft Function |
| NCT06199427 | PHASE2 | RECRUITING | PTCy and and Ruxolitinib for GVHD Prophylaxis After HSCT With Thymoglobulin in Conditioning Regimen in Patients With Inborn Errors of Immunity |
| NCT00253539 | PHASE2 | COMPLETED | Arzoxifene or Tamoxifen in Preventing Breast Cancer in Premenopausal Women at High Risk for Breast Cancer |
| NCT00305695 | PHASE2 | COMPLETED | Zoledronate or Observation in Maintaining Bone Mineral Density in Patients Who Are Undergoing Surgery to Remove Both Ovaries |
| NCT00321633 | PHASE2 | COMPLETED | Carboplatin or Docetaxel in Treating Women With Metastatic Genetic Breast Cancer |
| NCT01333748 | PHASE2 | COMPLETED | Search Allelic Imbalance of Expression of BRCA Genes in Hereditary Risk of Breast and/or Ovarian Cancer |
| NCT01367639 | PHASE2 | COMPLETED | Trial of Inquiry Based Stress Reduction (IBSR) Program for BRCA1/2 Mutation Carriers |
| NCT00535119 | PHASE1 | COMPLETED | Veliparib, Carboplatin, and Paclitaxel in Treating Patients With Advanced Solid Cancer |
| NCT00892736 | PHASE1 | COMPLETED | Veliparib in Treating Patients With Malignant Solid Tumors That Do Not Respond to Previous Therapy |
| NCT00001158 | Not specified | COMPLETED | Studies of the Immune Response in Normal Subjects and Patients With Disorders of the Immune System |
| NCT00001336 | Not specified | COMPLETED | In Vitro Studies of Immunological and Stem Cell Function in Peripheral Blood Mononuclear Cells in Patients |
| NCT00001788 | Not specified | TERMINATED | Genetic Basis of Primary Immunodeficiencies |
| NCT00006054 | Not specified | TERMINATED | Allogeneic Bone Marrow Transplantation in Patients With Primary Immunodeficiencies |
| NCT00006131 | Not specified | COMPLETED | Randomized Study of Two Doses of Oral Valacyclovir in Immunocompromised Patients With Uncomplicated Herpes Zoster |
| NCT01150240 | Not specified | UNKNOWN | Clinical and Laboratory Online Patient- and Research Database for Primary Immunodeficiencies in Switzerland |
| NCT01727895 | Not specified | COMPLETED | Effects of Orally Administered Beta-glucan on Leukocyte Function in Humans |
Related Atlas pages
- Associated diseases: immunodeficiency 57, autoinflammation with episodic fever and lymphadenopathy, immune dysregulation-inflammatory bowel disease-arthritis-recurrent infections-lymphopenia syndrome
- Targeted by drugs: Ponatinib
- Disease cohort memberships (association, not causation — diseases whose associated-gene cohort lists this gene; a subset are also under Associated diseases): autoinflammation with episodic fever and lymphadenopathy, hereditary breast ovarian cancer syndrome, IL10-related early-onset inflammatory bowel disease, immune dysregulation-inflammatory bowel disease-arthritis-recurrent infections-lymphopenia syndrome, immunodeficiency 57, inborn error of immunity