CASP1

Summary

CASP1 (caspase 1, HGNC:1499) is a protein-coding gene on chromosome 11q22.3, encoding Caspase-1 (P29466). Thiol protease involved in a variety of inflammatory processes by proteolytically cleaving other proteins, such as the precursors of the inflammatory cytokines interleukin-1 beta (IL1B) and interleukin 18 (IL18) as well as the pyroptosis inducer Gasdermin-D (GSDMD), into active….

This gene encodes a protein which is a member of the cysteine-aspartic acid protease (caspase) family. Sequential activation of caspases plays a central role in the execution-phase of cell apoptosis. Caspases exist as inactive proenzymes which undergo proteolytic processing at conserved aspartic residues to produce 2 subunits, large and small, that dimerize to form the active enzyme. This gene was identified by its ability to proteolytically cleave and activate the inactive precursor of interleukin-1, a cytokine involved in the processes such as inflammation, septic shock, and wound healing. This gene has been shown to induce cell apoptosis and may function in various developmental stages. Studies of a similar gene in mouse suggest a role in the pathogenesis of Huntington disease. Alternative splicing results in transcript variants encoding distinct isoforms.

Source: NCBI Gene 834 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 83 total
• Druggable target: yes — 43 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_001257118

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:1499
Approved symbol	CASP1
Name	caspase 1
Location	11q22.3
Locus type	gene with protein product
Status	Approved
Aliases	ICE
Ensembl gene	ENSG00000137752
Ensembl biotype	protein_coding
OMIM	147678
Entrez	834

Gene structure

Transcript identifiers

Ensembl transcripts: 25 — 19 protein_coding, 3 retained_intron, 3 nonsense_mediated_decay

ENST00000436863, ENST00000525825, ENST00000526511, ENST00000526568, ENST00000527625, ENST00000527979, ENST00000528424, ENST00000528974, ENST00000529871, ENST00000531166, ENST00000532439, ENST00000533400, ENST00000534497, ENST00000695714, ENST00000695715, ENST00000695716, ENST00000695717, ENST00000695718, ENST00000695719, ENST00000695720, ENST00000695721, ENST00000695722, ENST00000904258, ENST00000904259, ENST00000904260

RefSeq mRNA: 7 — MANE Select: NM_001257118 NM_001223, NM_001257118, NM_001257119, NM_033292, NM_033293, NM_033294, NM_033295

CCDS: CCDS53704, CCDS8329, CCDS8330, CCDS8331, CCDS8332

Canonical transcript exons

ENST00000533400 — 9 exons

Exon	Start	End
ENSE00000795390	105026842	105026951
ENSE00002147295	105025508	105026356
ENSE00003845168	105035107	105035144
ENSE00003964809	105034208	105034474
ENSE00003964813	105030330	105030503
ENSE00003964814	105033064	105033126
ENSE00003964815	105029124	105029267
ENSE00003964817	105031165	105031280
ENSE00003964819	105029665	105029899

Expression profiles

Bgee: expression breadth ubiquitous, 262 present calls, max score 99.56.

FANTOM5 (CAGE): breadth broad, TPM avg 6.3088 / max 153.0401, expressed in 891 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
122081	6.0636	883
122080	0.2452	94

Top tissues by expression

289 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
monocyte	CL:0000576	99.56	gold quality
mononuclear cell	CL:0000842	99.46	gold quality
leukocyte	CL:0000738	99.42	gold quality
granulocyte	CL:0000094	98.77	gold quality
blood	UBERON:0000178	97.67	gold quality
jejunal mucosa	UBERON:0000399	97.30	gold quality
spleen	UBERON:0002106	96.84	gold quality
vermiform appendix	UBERON:0001154	95.94	gold quality
ileal mucosa	UBERON:0000331	95.61	gold quality
duodenum	UBERON:0002114	95.33	gold quality
rectum	UBERON:0001052	95.14	gold quality
small intestine Peyer’s patch	UBERON:0003454	94.76	gold quality
stromal cell of endometrium	CL:0002255	94.41	gold quality
small intestine	UBERON:0002108	94.22	gold quality
mucosa of transverse colon	UBERON:0004991	93.77	gold quality
caecum	UBERON:0001153	93.55	gold quality
gall bladder	UBERON:0002110	93.28	gold quality
mucosa of sigmoid colon	UBERON:0004993	93.09	gold quality
lymph node	UBERON:0000029	93.08	gold quality
upper lobe of left lung	UBERON:0008952	92.92	gold quality
bone marrow cell	CL:0002092	92.86	gold quality
epithelium of nasopharynx	UBERON:0001951	92.83	gold quality
upper lobe of lung	UBERON:0008948	92.79	gold quality
colonic mucosa	UBERON:0000317	92.74	gold quality
bone marrow	UBERON:0002371	92.67	gold quality
right lung	UBERON:0002167	92.62	gold quality
lower lobe of lung	UBERON:0008949	92.52	gold quality
colonic epithelium	UBERON:0000397	91.30	gold quality
lung	UBERON:0002048	90.93	gold quality
pleura	UBERON:0000977	90.84	gold quality

Single-cell (SCXA)

Detected in 7 experiment(s), a significant marker in 7.

Experiment	Marker?	Max mean expression
E-MTAB-6701	yes	28.65
E-CURD-112	yes	25.34
E-GEOD-125970	yes	22.30
E-MTAB-8498	yes	9.89
E-MTAB-6678	yes	8.12
E-MTAB-9801	yes	6.58
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): BCL6, EGR1, ETS1, FOXO3, IRF1, IRF2, JUN, MAFA, MYC, NFE2L2, NFKB, NFYA, NR0B2, PARP1, RNF2, SSRP1, TP53, TP63, TP73

miRNA regulators (miRDB)

10 targeting CASP1, 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-4795-3P	100.00	74.62	4024
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-485-3P	99.98	70.68	1585
HSA-MIR-539-3P	99.98	70.74	1616
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-205-3P	99.92	69.92	3165
HSA-MIR-153-5P	99.89	73.86	6317
HSA-MIR-561-3P	99.64	70.90	3647
HSA-MIR-4291	99.20	68.88	2969
HSA-MIR-922	99.02	67.23	1838

Literature-anchored findings (GeneRIF, showing 40)

• CARD-8 protein, a new CARD family member that regulates caspase-1 activation and apoptosis. (PMID:11821383)
• The PYRIN-CARD protein ASC is an activating adaptor for caspase-1. (PMID:11967258)
• regulation of activation of caspase-1-dependent cytokine processing by PYPAF7 (PMID:12019269)
• Interleukin-1F7B (IL-1H4/IL-1F7) is processed by this enzyme (PMID:12096920)
• The caspase-1 level was significantly higher in biochemorefractory melanoma patients compared with responders, suggesting that disrupted apoptosis pathways might be involved in the progressive disease and drug resistance. (PMID:12170183)
• inflammasome comprises caspase-1, caspase-5, Pycard/Asc, and NALP1; a molecular platform triggering activation of inflammatory caspases and processing of proIL-beta (PMID:12191486)
• Differential rates of frameshift alterations in four repeat sequences of hereditary nonpolyposis colorectal cancer tumors.These repeats consisted of (A)10 in the TGF beta RII, (G)8 in the BAX, (A)8 in the CASP1, and (CCA)7 in the APP genes. (PMID:12215842)
• activation in immune cells by PYPAF5 (PMID:12387869)
• Caspase 1 has a role in T-cell protein tyrosine phosphatase-induced apoptosis in a human tumor cell line. (PMID:12459463)
• Exposure to a cytotoxic concentration of gp120 up-regulates expression of the inducible isoform of cyclooxygenase (COX-2) in neuroblastoma cells and this is blocked by caspase 1 inhibitors (PMID:12628757)
• Caspases responsible for parkin cleavage were identified by several experimental paradigms exploring the anti-Fas induced pathway and tnf-alpha pathway. (PMID:12692130)
• Data show that gingival fibroblasts express interleukin-1 (IL_1) beta converting enzyme mRNA, but low levels of IL-1 beta mRNA, and do not secrete interleukin-18. (PMID:14584052)
• Overexpression of Caspase-1 is a frequent event in pancreatic disorders and neoplasms. (PMID:14669344)
• caspase-1 contributes to inflammation by two distinct pathways: proteolysis of pro-IL-1beta, and RIP2-dependent activation of NF-kappaB and p38 MAPK mediated by the caspase recruitment domain (PMID:15039421)
• resistance of pro-interleukin-18 to processing by caspase 1 in ovarian tumors (PMID:15326478)
• expression of caspase-1 and IL-18 was significantly increased in multiple sclerosis patients (PMID:15471361)
• NF-kappaB- and C/EBPbeta-driven interleukin-1beta gene expression and PAK1-mediated caspase-1 activation play essential roles in interleukin-1beta release from Helicobacter pylori lipopolysaccharide-stimulated macrophages (PMID:15561713)
• epigenetic events such as DNA methylation and histone deacetylation play important roles in the regulation of caspase-1, and loss of caspase-1 expression is associated with poor survival in gastric carcinoma (PMID:15809717)
• data suggest that both pyrin and cryopyrin are capable of assembling independent inflammasome complexes with ASC and procaspase-1, and activating caspase-1 via ASC oligomerization (PMID:16037825)
• VLDL induces IL-1beta mRNA expression, caspase-1 activation, and IL-1beta release from macrophages (PMID:16087165)
• results show that Csp-1 is an upstream positive regulator of Csp-6-mediated cell death in primary human neurons; also results suggest that the activation of Csp-1 must be accompanied by an apoptotic insult to induce Csp-6-mediated cell death (PMID:16123779)
• IL-32 synergizes with nucleotide oligomerization domain (NOD) 1 and NOD2 ligands for IL-1beta and IL-6 production through a caspase 1-dependent mechanism. (PMID:16260731)
• Interleukin-1 Beta gene polymorphism is associated with precancerous lesions in African Americans and Caucasians. (PMID:16405550)
• Increased plasma levels of caspase-1 is associated with cutaneous T-cell lymphoma (PMID:16428475)
• proinflammatory response mediated by statins in activated peripheral blood mononuclear cells is mediated mainly via the activation of caspase-1 and interleukin-18 secretion in the monocytes and to a lesser extent by interleukin-12 (PMID:16621994)
• Data show that expression of Caspase-1 was significantly increased in the hippocampus of the developing recurrent seizures rats. (PMID:16780720)
• The C-terminal B30.2 domain of pyrin is necessary and sufficient for the interaction with caspase-1 to modulate IL-1beta production. (PMID:16785446)
• Involvement of caspase 1 and its activator Ipaf upstream of mitochondrial events in apoptosis (PMID:16817903)
• IL-32 is a cell-associated proinflammatory cytokine, which is specifically stimulated by mycobacteria through a caspase-1- and IL-18-dependent production of interferon gamma. (PMID:16903774)
• Cop inhibition of cell death, at least to a certain extent, results from its interference with the activation of caspase-1 and caspase-4. (PMID:16920334)
• pannexin-1 is required for processing of caspase-1 and release of mature IL-1beta induced by P2X(7) receptor activation. (PMID:17036048)
• In summary, we showed that HIPPI could interact with the putative promoter sequence of caspase-1 and increased the expression of the downstream gene suggesting that HIPPI could act as transcription regulator. (PMID:17173859)
• Caspase-1 is upregulated in human heart failure and acts as a potent proapoptotic caspase both in isolated human cardiomyocytes and in vivo. (PMID:17303764)
• Caspase-1 plays a role in the regulation of Toll-like receptors-2 and -4 signaling pathways via an effect on MyD88 adapter-like protein. (PMID:17360653)
• Antiapoptotic proteins Bcl-2 and Bcl-X(L) bind and suppress NALP1, reducing caspase-1 activation and interleukin-1beta (IL-1beta) production. (PMID:17418785)
• the activity of caspase-1 is increased in psoriatic skin and IL-18 secretion is regulated by a p38 MAPK/caspase-1-dependent mechanism (PMID:17597823)
• identification of a novel function of HIPPI; it binds to specific upstream sequences of the caspase-1, caspase-8 and caspase-10 genes and alters the expression of the genes (PMID:17623017)
• characterization of caspase-1 substrates identifies the glycolysis pathway as a caspase-1 target and provides new insights into its function during pyroptosis and septic shock. (PMID:17959595)
• Triggering of cytosolic RNA recognition pathway with poly(I:C) transfection or influenza A virus infection resulted in caspase-1- and -3-mediated proteolytic processing of pro-IL-18 and secretion of biologically active IL-18. (PMID:18209072)
• up-regulated in pancreatic sections and in isolated islets from type 2 diabetic patients (PMID:18263705)

Cross-species orthologs

12 orthologs

Organism	Symbol	Gene ID
danio_rerio	casp8	ENSDARG00000058325
danio_rerio	casp3l	ENSDARG00000086266
danio_rerio	casp20	ENSDARG00000104367
danio_rerio		ENSDARG00000112575
mus_musculus	Casp1	ENSMUSG00000025888
rattus_norvegicus	Casp1	ENSRNOG00000007372
drosophila_melanogaster	Dronc	FBGN0026404
drosophila_melanogaster	Decay	FBGN0028381
caenorhabditis_elegans		WBGENE00000417
caenorhabditis_elegans		WBGENE00000819
caenorhabditis_elegans		WBGENE00000820
caenorhabditis_elegans	csp-3	WBGENE00000821

Paralogs (16): CASP10 (ENSG00000003400), CFLAR (ENSG00000003402), CASP8 (ENSG00000064012), PYCARD (ENSG00000103490), CASP14 (ENSG00000105141), CASP2 (ENSG00000106144), CASP9 (ENSG00000132906), CASP5 (ENSG00000137757), CASP6 (ENSG00000138794), CASP3 (ENSG00000164305), CASP7 (ENSG00000165806), PYDC1 (ENSG00000169900), CASP4 (ENSG00000196954), CARD16 (ENSG00000204397), CASP12 (ENSG00000204403), CARD18 (ENSG00000255501)

Protein

Protein identifiers

Caspase-1 — P29466 (reviewed: P29466)

Alternative names: Interleukin-1 beta convertase, Interleukin-1 beta-converting enzyme, p45

All UniProt accessions (9): P29466, A0A8Q3SI00, A0A8Q3SI67, A0A8Q3SIY2, B4DKN4, B4DVD8, G3V169, H0YEC7, Q5FBZ0

UniProt curated annotations — full annotation on UniProt →

Function. Thiol protease involved in a variety of inflammatory processes by proteolytically cleaving other proteins, such as the precursors of the inflammatory cytokines interleukin-1 beta (IL1B) and interleukin 18 (IL18) as well as the pyroptosis inducer Gasdermin-D (GSDMD), into active mature peptides. Plays a key role in cell immunity as an inflammatory response initiator: once activated through formation of an inflammasome complex, it initiates a pro-inflammatory response through the cleavage of the two inflammatory cytokines IL1B and IL18, releasing the mature cytokines which are involved in a variety of inflammatory processes. Cleaves a tetrapeptide after an Asp residue at position P1. Also initiates pyroptosis, a programmed lytic cell death pathway, through cleavage of GSDMD. In contrast to cleavage of interleukin IL1B, recognition and cleavage of GSDMD is not strictly dependent on the consensus cleavage site but depends on an exosite interface on CASP1 that recognizes and binds the Gasdermin-D, C-terminal (GSDMD-CT) part. Cleaves and activates CASP7 in response to bacterial infection, promoting plasma membrane repair. Upon inflammasome activation, during DNA virus infection but not RNA virus challenge, controls antiviral immunity through the cleavage of CGAS, rendering it inactive. In apoptotic cells, cleaves SPHK2 which is released from cells and remains enzymatically active extracellularly. Apoptosis inactive. Apoptosis inactive.

Subunit / interactions. Heterotetramer that consists of two anti-parallel arranged heterodimers, each one formed by a 20 kDa (Caspase-1 subunit p20) and a 10 kDa (Caspase-1 subunit p10) subunit. May be a component of the inflammasome, a protein complex which also includes PYCARD, CARD8 and NLRP2 and whose function would be the activation of pro-inflammatory caspases. Component of the AIM2 PANoptosome complex, a multiprotein complex that drives inflammatory cell death (PANoptosis). Interacts with CARD8; interacts with the released C-terminus of CARD8 which forms an inflammasome and directly activates CASP1 to promote pyroptosis. Both the p10 and p20 subunits interact with MEFV. Interacts with CARD17P/INCA and CARD18. Interacts with SERPINB1; this interaction regulates CASP1 activity. Heterotetramer that consists of two anti-parallel arranged heterodimers, each one formed by a 20 kDa (Caspase-1 subunit p20) and a 10 kDa (Caspase-1 subunit p10) subunit. Can form a heterodimer with isoform epsilon which then has an inhibitory effect. Heterotetramer that consists of two anti-parallel arranged heterodimers, each one formed by a 20 kDa (Caspase-1 subunit p20) and a 10 kDa (Caspase-1 subunit p10) subunit. Can form a heterodimer with Caspase-1 subunit p20 which then has an inhibitory effect.

Subcellular location. Cytoplasm. Cell membrane.

Tissue specificity. Expressed in larger amounts in spleen and lung. Detected in liver, heart, small intestine, colon, thymus, prostate, skeletal muscle, peripheral blood leukocytes, kidney and testis. No expression in the brain.

Post-translational modifications. The two subunits are derived from the precursor sequence by an autocatalytic mechanism. Ubiquitinated via ‘Lys-11’-linked polyubiquitination. Deubiquitinated by USP8. Cleavage in the interdomain linker region is required to induce pyroptosis.

Activity regulation. (Microbial infection) Specifically inhibited by the cowpox virus Crma protein.

Induction. Transcription and translation induced by M.tuberculosis and a number of different M.tuberculosis components; EsxA is the most potent activator tested (at protein level).

Similarity. Belongs to the peptidase C14A family.

Isoforms (5)

UniProt ID	Names	Canonical?
P29466-1	Alpha	yes
P29466-2	Beta
P29466-3	Gamma
P29466-4	Delta
P29466-5	Epsilon

RefSeq proteins (7): NP_001214, NP_001244047, NP_001244048, NP_150634, NP_150635, NP_150636, NP_150637 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001309	Pept_C14_p20	Domain
IPR001315	CARD	Domain
IPR002138	Pept_C14_p10	Domain
IPR002398	Pept_C14	Family
IPR011029	DEATH-like_dom_sf	Homologous_superfamily
IPR011600	Pept_C14_caspase	Domain
IPR015917	Pept_C14A	Domain
IPR016129	Caspase_his_AS	Active_site
IPR029030	Caspase-like_dom_sf	Homologous_superfamily
IPR033139	Caspase_cys_AS	Active_site

Pfam: PF00619, PF00656

Enzyme classification (BRENDA):

• EC 3.4.22.36 — caspase-1 (BRENDA: 17 organisms, 274 substrates, 222 inhibitors, 49 Km, 41 kcat entries)

Substrate kinetics (BRENDA)

34 substrates with measured Km, best-characterized 15. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
AC-FEAD-7-AMIDO-4-CARBAMOYLMETHYLCOUMARIN	0.021	2
AC-WEHD-7-AMIDO-4-TRIFLUOROMETHYLCOUMARIN	0.038	2
AC-WQPD-7-AMIDO-4-CARBAMOYLMETHYLCOUMARIN	0.0115–0.016	2
ACETYL-LEVD-4-NITROANILIDE	0.0085–0.018	2
ACETYL-WEHD-7-AMIDO-4-METHYLCOUMARIN	0.004–0.038	2
LLSDGID	0.022	2
LSDGIDE	0.115	2
SDGIDEE	0.038	2
SLLSDG	0.087	2
SLLSDGI	0.052	2
SLLSDGID	0.049	2
SLLSDGIDE	0.038	2
SLLSDGIDEE	0.047	2
SUCCINYL-YVAD-4-NITROANILIDE	—	2
4-[[4’-(DIMETHYLAMINO)PHENYL]AZO]-BENZOIC ACID-Y	—	1

UniProt features (54 total): strand 16, helix 10, mutagenesis site 7, turn 5, splice variant 4, propeptide 2, chain 2, sequence conflict 2, active site 2, sequence variant 1, domain 1, modified residue 1, cross-link 1

Structure

Experimental structures (PDB)

42 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
8WRA	X-RAY DIFFRACTION	1.45
6BZ9	X-RAY DIFFRACTION	1.8
1SC3	X-RAY DIFFRACTION	1.8
2H54	X-RAY DIFFRACTION	1.8
2HBQ	X-RAY DIFFRACTION	1.8
3D6M	X-RAY DIFFRACTION	1.8
6F6R	X-RAY DIFFRACTION	1.8
1RWX	X-RAY DIFFRACTION	1.85
2H4Y	X-RAY DIFFRACTION	1.9
2HBZ	X-RAY DIFFRACTION	1.9
3D6F	X-RAY DIFFRACTION	1.9
6PZP	X-RAY DIFFRACTION	1.94
1RWN	X-RAY DIFFRACTION	2
2H4W	X-RAY DIFFRACTION	2
3D6H	X-RAY DIFFRACTION	2
3E4C	X-RAY DIFFRACTION	2.05
1RWO	X-RAY DIFFRACTION	2.1
1RWV	X-RAY DIFFRACTION	2.1
1SC4	X-RAY DIFFRACTION	2.1
2H51	X-RAY DIFFRACTION	2.1
2HBY	X-RAY DIFFRACTION	2.1
5MMV	X-RAY DIFFRACTION	2.15
1RWP	X-RAY DIFFRACTION	2.2
2H48	X-RAY DIFFRACTION	2.2
2HBR	X-RAY DIFFRACTION	2.2
1RWK	X-RAY DIFFRACTION	2.3
1BMQ	X-RAY DIFFRACTION	2.5
5MTK	X-RAY DIFFRACTION	2.53
1ICE	X-RAY DIFFRACTION	2.6
1SC1	X-RAY DIFFRACTION	2.6

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P29466-F1	82.48	0.58

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): 237; 285

Post-translational modifications (2): 302, 134

Mutagenesis-validated functional residues (7):

Position	Phenotype
285	loss of protease activity. loss of sphk2 cleavage and release in apoptotic cells.
294	mediates autoprocessing but is unable to interact with gasdermin-d (gsdmd) and mediate its cleavage.
297	in idl(uncl); abolished cleavage in the interdomain region; when associated with 315-n-n-316.
315–316	in idl(uncl); abolished cleavage in the interdomain region; when associated with n-297.
318–320	abolished ability to cleave il18.
318	mediates autoprocessing but is unable to interact with gasdermin-d (gsdmd) and mediate its cleavage.
320	abolishes cleavage of gasdermin-d (gsdmd).

Function

Pathways and Gene Ontology

Reactome pathways

34 pathways

ID	Pathway
R-HSA-168638	NOD1/2 Signaling Pathway
R-HSA-448706	Interleukin-1 processing
R-HSA-5620971	Pyroptosis
R-HSA-6803207	TP53 Regulates Transcription of Caspase Activators and Caspases
R-HSA-844456	The NLRP3 inflammasome
R-HSA-844615	The AIM2 inflammasome
R-HSA-844623	The IPAF inflammasome
R-HSA-9008059	Interleukin-37 signaling
R-HSA-9660826	Purinergic signaling in leishmaniasis infection
R-HSA-9692916	SARS-CoV-1 activates/modulates innate immune responses
R-HSA-9968551	Regulation of GBP-mediated host defense
R-HSA-1280215	Cytokine Signaling in Immune system
R-HSA-1643685	Disease
R-HSA-168249	Innate Immune System
R-HSA-168256	Immune System
R-HSA-168643	Nucleotide-binding domain, leucine rich repeat containing receptor (NLR) signaling pathways
R-HSA-212436	Generic Transcription Pathway
R-HSA-3700989	Transcriptional Regulation by TP53
R-HSA-446652	Interleukin-1 family signaling
R-HSA-449147	Signaling by Interleukins
R-HSA-5218859	Regulated Necrosis
R-HSA-5357801	Programmed Cell Death
R-HSA-5633008	TP53 Regulates Transcription of Cell Death Genes
R-HSA-5663205	Infectious disease
R-HSA-622312	Inflammasomes
R-HSA-73857	RNA Polymerase II Transcription
R-HSA-74160	Gene expression (Transcription)
R-HSA-9658195	Leishmania infection
R-HSA-9664424	Cell recruitment (pro-inflammatory response)
R-HSA-9678108	SARS-CoV-1 Infection

MSigDB gene sets: 581 (showing top): MODULE_172, WANG_CLIM2_TARGETS_UP, JI_RESPONSE_TO_FSH_UP, REACTOME_INNATE_IMMUNE_SYSTEM, REACTOME_NOD1_2_SIGNALING_PATHWAY, REACTOME_CYTOKINE_SIGNALING_IN_IMMUNE_SYSTEM, GOBP_INFLAMMATORY_RESPONSE, REACTOME_THE_NLRP3_INFLAMMASOME, GOBP_RESPONSE_TO_PEPTIDE, GOBP_CELLULAR_RESPONSE_TO_LIPID, REACTOME_INFLAMMASOMES, GOBP_CELLULAR_RESPONSE_TO_EXTERNAL_STIMULUS, REACTOME_NUCLEOTIDE_BINDING_DOMAIN_LEUCINE_RICH_REPEAT_CONTAINING_RECEPTOR_NLR_SIGNALING_PATHWAYS, ENK_UV_RESPONSE_KERATINOCYTE_UP, GOBP_CELLULAR_RESPONSE_TO_BIOTIC_STIMULUS

GO Biological Process (36): pattern recognition receptor signaling pathway (GO:0002221), proteolysis (GO:0006508), apoptotic process (GO:0006915), signal transduction (GO:0007165), osmosensory signaling pathway (GO:0007231), protein autoprocessing (GO:0016540), positive regulation of interleukin-1 beta production (GO:0032731), positive regulation of interleukin-18 production (GO:0032741), defense response to bacterium (GO:0042742), regulation of apoptotic process (GO:0042981), positive regulation of canonical NF-kappaB signal transduction (GO:0043123), icosanoid biosynthetic process (GO:0046456), regulation of inflammatory response (GO:0050727), positive regulation of inflammatory response (GO:0050729), protein maturation (GO:0051604), defense response to virus (GO:0051607), pyroptotic inflammatory response (GO:0070269), cellular response to lipopolysaccharide (GO:0071222), cellular response to mechanical stimulus (GO:0071260), cellular response to type II interferon (GO:0071346), cytokine precursor processing (GO:0140447), signaling receptor ligand precursor processing (GO:0140448), AIM2 inflammasome complex assembly (GO:0140970), positive regulation of tumor necrosis factor-mediated signaling pathway (GO:1903265), negative regulation of transcription by RNA polymerase II (GO:0000122), plasma membrane repair (GO:0001778), inflammatory response (GO:0006954), protein secretion (GO:0009306), protein catabolic process (GO:0030163), response to lipopolysaccharide (GO:0032496), regulation of interleukin-1 beta production (GO:0032651), interleukin-18-mediated signaling pathway (GO:0035655), ceramide biosynthetic process (GO:0046513), protein poly-ADP-ribosylation (GO:0070212), interleukin-1-mediated signaling pathway (GO:0070498), pyroptotic cell death (GO:0141201)

GO Molecular Function (12): endopeptidase activity (GO:0004175), cysteine-type endopeptidase activity (GO:0004197), cysteine-type endopeptidase activator activity involved in apoptotic process (GO:0008656), kinase binding (GO:0019900), cytokine binding (GO:0019955), identical protein binding (GO:0042802), CARD domain binding (GO:0050700), protein binding (GO:0005515), peptidase activity (GO:0008233), cysteine-type peptidase activity (GO:0008234), hydrolase activity (GO:0016787), enzyme binding (GO:0019899)

GO Cellular Component (13): nucleolus (GO:0005730), cytoplasm (GO:0005737), cytosol (GO:0005829), microtubule (GO:0005874), plasma membrane (GO:0005886), protein-containing complex (GO:0032991), canonical inflammasome complex (GO:0061702), IPAF inflammasome complex (GO:0072557), NLRP1 inflammasome complex (GO:0072558), NLRP3 inflammasome complex (GO:0072559), AIM2 inflammasome complex (GO:0097169), protease inhibitor complex (GO:0097179), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-14 pathways:

Category	Pathways
Inflammasomes	3
Interleukin-1 family signaling	2
Immune System	2
Nucleotide-binding domain, leucine rich repeat containing receptor (NLR) signaling pathways	1
Regulated Necrosis	1
TP53 Regulates Transcription of Cell Death Genes	1
Cell recruitment (pro-inflammatory response)	1
SARS-CoV-1-host interactions	1
GBP-mediated host defense	1
Innate Immune System	1
RNA Polymerase II Transcription	1
Generic Transcription Pathway	1
Signaling by Interleukins	1
Cytokine Signaling in Immune system	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
canonical inflammasome complex	4
inflammatory response	3
protein binding	3
cellular anatomical structure	3
protein metabolic process	2
defense response	2
peptidase activity	2
innate immune response-activating signaling pathway	1
programmed cell death	1
apoptotic signaling pathway	1
execution phase of apoptosis	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
intracellular signal transduction	1
cellular response to osmotic stress	1
protein processing	1
interleukin-1 beta production	1
regulation of interleukin-1 beta production	1
positive regulation of interleukin-1 production	1
positive regulation of cytokine production	1
interleukin-18 production	1
regulation of interleukin-18 production	1
response to bacterium	1
apoptotic process	1
regulation of programmed cell death	1
canonical NF-kappaB signal transduction	1
regulation of canonical NF-kappaB signal transduction	1
positive regulation of intracellular signal transduction	1
icosanoid metabolic process	1
carboxylic acid biosynthetic process	1
regulation of defense response	1
regulation of response to external stimulus	1
positive regulation of defense response	1
positive regulation of response to external stimulus	1
regulation of inflammatory response	1
gene expression	1
response to virus	1

Protein interactions and networks

STRING

4052 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CASP1	MEFV	O15553	999
CASP1	PYCARD	Q9ULZ3	999
CASP1	NLRP3	Q96P20	999
CASP1	AIM2	O14862	999
CASP1	NLRC4	Q9NPP4	999
CASP1	NLRP1	Q9C000	999
CASP1	NLRP6	P59044	994
CASP1	NLRP12	P59046	989
CASP1	IL1B	P01584	988
CASP1	CASP8	Q14790	986
CASP1	CASP5	P51878	984
CASP1	IL18	Q14116	979
CASP1	NLRP2	Q9NX02	975
CASP1	CARD8	Q9Y2G2	973
CASP1	XIAP	P98170	959

IntAct

65 interactions, top by confidence:

A	B	Type	Score
PYCARD	CASP1	psi-mi:“MI:0914”(association)	0.860
PYCARD	CASP1	psi-mi:“MI:0915”(physical association)	0.860
PYCARD	CASP1	psi-mi:“MI:0407”(direct interaction)	0.860
CASP1	PYCARD	psi-mi:“MI:0407”(direct interaction)	0.860
NLRC4	CASP1	psi-mi:“MI:0915”(physical association)	0.740
CASP1	NLRC4	psi-mi:“MI:0915”(physical association)	0.740
VAC14	CASP1	psi-mi:“MI:0915”(physical association)	0.670
CASP1	VAC14	psi-mi:“MI:0915”(physical association)	0.670
CASP1	NLRP1	psi-mi:“MI:0915”(physical association)	0.660
GSDMD	N	psi-mi:“MI:0914”(association)	0.660
CASP1	CARD18	psi-mi:“MI:0407”(direct interaction)	0.600
CASP1	NOD2	psi-mi:“MI:0915”(physical association)	0.590
NOD2	CASP1	psi-mi:“MI:0915”(physical association)	0.590
CASP1	CASP1	psi-mi:“MI:0407”(direct interaction)	0.590
CASP1	CARD17P	psi-mi:“MI:0915”(physical association)	0.590
CASP1	CARD17P	psi-mi:“MI:0407”(direct interaction)	0.590

BioGRID (113): ced-4 (Affinity Capture-Western), CASP1 (Affinity Capture-Western), CASP1 (Affinity Capture-Western), VAC14 (Two-hybrid), KIF3A (Affinity Capture-MS), KIF11 (Affinity Capture-MS), GAB1 (Affinity Capture-MS), ARID4B (Affinity Capture-MS), PI4KB (Affinity Capture-MS), FMN2 (Affinity Capture-MS), CASP1 (Reconstituted Complex), CASP1 (Affinity Capture-Western), CARD16 (Affinity Capture-Western), CASP1 (Affinity Capture-Western), CASP1 (Affinity Capture-Western)

ESM2 similar proteins: A0A1D5PPP7, F1NV61, O01382, O08738, O35397, O75601, O88600, O95757, P00860, P11926, P14019, P17706, P27117, P27119, P27120, P29452, P29466, P34932, P35233, P42574, P43527, P48722, P55210, P55212, P55213, P55214, P55866, P70677, P89116, P97864, Q06180, Q08DY9, Q14790, Q2PFV2, Q2TFN9, Q3T0P5, Q5E9C1, Q5IS54, Q5IS99, Q5RDM4

Diamond homologs: O08736, O35397, O75601, P29452, P29466, P42574, P43527, P49662, P51878, P55212, P55213, P55865, P55867, P70343, P70677, Q075B4, Q08DY9, Q153Z0, Q2PFV2, Q504J1, Q5E9C1, Q5IS54, Q5IS99, Q60431, Q6UXS9, Q8MJC3, Q8MJU1, Q8MKI5, Q920D5, Q95ND5, Q9I9L7, Q9MZV6, Q9MZV7, Q9N2I1, Q9TV13, A0A1D5PPP7, F1NV61, G5ECW5, O01382, O02002

SIGNOR signaling

14 interactions.

A	Effect	B	Mechanism
VX-765	down-regulates	CASP1	“chemical inhibition”
CASP1	“up-regulates activity”	SPHK2	binding
RNF31	“up-regulates activity”	CASP1	polyubiquitination
CASP1	“down-regulates activity”	RNF31	cleavage
CASP1	“form complex”	“Caspase 1 complex”	binding
CASP1	“form complex”	“AIM2 inflammasome”	binding
CASP1	“form complex”	“NLRC4 inflammasome”	binding
CASP1	“form complex”	“NLRP1 inflammasome”	binding
CASP1	“form complex”	“NLRP3 inflammasome”	binding
CASP1	“form complex”	“Pyrin inflammasome”	binding
CASP1	“up-regulates activity”	PSEN2	cleavage
CASP1	“up-regulates activity”	PSEN1	cleavage

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 26 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
Purinergic signaling in leishmaniasis infection	5	111.3×	9e-08

GO biological processes:

GO term	Partners	Fold	FDR
pattern recognition receptor signaling pathway	6	270.4×	7e-12
pyroptotic inflammatory response	6	139.3×	2e-10
positive regulation of interleukin-1 beta production	8	94.3×	5e-12
positive regulation of interleukin-6 production	8	60.7×	6e-11
positive regulation of interleukin-8 production	5	55.5×	1e-06
positive regulation of inflammatory response	8	52.8×	1e-10
positive regulation of tumor necrosis factor production	7	48.8×	5e-09
obsolete positive regulation of NF-kappaB transcription factor activity	5	46.7×	2e-06

Disease & clinical

Clinical variants and AI predictions

ClinVar

83 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	51
Likely benign	12
Benign	3

Top pathogenic / likely-pathogenic (0)

SpliceAI

1261 predictions. Top by Δscore:

Variant	Effect	Δscore
11:105029896:TGTC:T	acceptor_gain	1.0000
11:105030325:CTT:C	donor_loss	1.0000
11:105030326:TTAC:T	donor_loss	1.0000
11:105030327:TA:T	donor_loss	1.0000
11:105030328:A:AC	donor_gain	1.0000
11:105030329:C:CT	donor_gain	1.0000
11:105030503:TC:T	acceptor_loss	1.0000
11:105030504:C:CA	acceptor_loss	1.0000
11:105030505:T:C	acceptor_loss	1.0000
11:105034202:CCTTA:C	donor_loss	1.0000
11:105034203:CTTA:C	donor_loss	1.0000
11:105034205:TACCT:T	donor_loss	1.0000
11:105034206:ACCTG:A	donor_loss	1.0000
11:105034207:C:CG	donor_loss	1.0000
11:105029118:TGTTA:T	donor_loss	0.9900
11:105029120:TTAC:T	donor_loss	0.9900
11:105029122:ACC:A	donor_loss	0.9900
11:105029123:C:CT	donor_loss	0.9900
11:105029264:CTGT:C	acceptor_gain	0.9900
11:105029265:TGT:T	acceptor_gain	0.9900
11:105029660:C:CG	donor_loss	0.9900
11:105029661:TCAC:T	donor_gain	0.9900
11:105029662:C:CC	donor_loss	0.9900
11:105029662:CACC:C	donor_gain	0.9900
11:105029663:ACCA:A	donor_gain	0.9900
11:105029664:C:CG	donor_loss	0.9900
11:105029664:CCAC:C	donor_gain	0.9900
11:105029815:C:CT	acceptor_gain	0.9900
11:105029895:ATGTC:A	acceptor_gain	0.9900
11:105029897:GTCC:G	acceptor_loss	0.9900

AlphaMissense

2678 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:105029840:G:C	S229R	0.996
11:105029840:G:T	S229R	0.996
11:105029842:T:G	S229R	0.996
11:105030438:A:C	F173L	0.991
11:105030438:A:T	F173L	0.991
11:105030440:A:G	F173L	0.991
11:105029873:A:C	F218L	0.985
11:105029873:A:T	F218L	0.985
11:105029875:A:G	F218L	0.985
11:105030460:A:G	L166P	0.983
11:105026313:G:T	P387H	0.982
11:105029699:T:A	K276N	0.982
11:105029699:T:G	K276N	0.982
11:105029693:C:A	K278N	0.981
11:105029693:C:G	K278N	0.981
11:105029697:G:T	P277Q	0.978
11:105029822:C:A	M235I	0.978
11:105029822:C:G	M235I	0.978
11:105029822:C:T	M235I	0.978
11:105030463:G:T	A165D	0.978
11:105029698:G:A	P277S	0.977
11:105026342:A:C	F377L	0.976
11:105026342:A:T	F377L	0.976
11:105026344:A:G	F377L	0.976
11:105029829:A:T	V233E	0.976
11:105029741:A:C	F262L	0.975
11:105029741:A:T	F262L	0.975
11:105029743:A:G	F262L	0.975
11:105030404:C:G	D185H	0.975
11:105026278:A:C	Y399D	0.974

dbSNP variants (sampled 300 via entrez): RS1000180195 (11:105029335 G>A,C,T), RS1000430093 (11:105037454 G>A), RS1000520699 (11:105027990 T>G), RS1000787732 (11:105031461 A>G), RS1001155887 (11:105033540 G>T), RS1001184366 (11:105030898 G>A), RS1001436844 (11:105033712 G>A,T), RS1001510447 (11:105025415 G>T), RS1001583402 (11:105027420 A>G), RS1001793078 (11:105032668 G>T), RS1002040002 (11:105034846 T>A,G), RS1002559111 (11:105034581 C>T), RS1002589916 (11:105035192 T>A,C), RS1002772836 (11:105029192 A>C,G), RS1002984865 (11:105028878 G>A)

Disease associations

OMIM: gene MIM:147678 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST008156_76	Hip circumference adjusted for BMI	5.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0008039	BMI-adjusted hip circumference

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL3831289 (PROTEIN FAMILY), CHEMBL4801 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

43 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 1,565,650 (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
CHEMBL107	COLCHICINE	4	93,932
CHEMBL1201038	ACRISORCIN	4	1,956
CHEMBL12856	INAMRINONE	4	9,690
CHEMBL1351	CARBOPLATIN	4
CHEMBL1410	NONOXYNOL 9	4	14,701
CHEMBL1447476	BITHIONOLATE SODIUM	4	324
CHEMBL1534	RIBOFLAVIN	4	136,163
CHEMBL1554	DACTINOMYCIN	4	175,245
CHEMBL1607	TOPOTECAN HYDROCHLORIDE	4	56,379
CHEMBL190461	CANNABIDIOL	4	26,379
CHEMBL255044	FLUPIRTINE	4	5,706
CHEMBL290106	BITHIONOL	4	6,439
CHEMBL34259	METHOTREXATE	4	398,396
CHEMBL374478	RIFAMPIN	4	93,834
CHEMBL421	SULFASALAZINE	4	73,629
CHEMBL43	AMSACRINE	4	82,326
CHEMBL43128	PRIMAQUINE PHOSPHATE	4	2,032
CHEMBL53463	DOXORUBICIN	4	314,282
CHEMBL585	TRIAMTERENE	4	21,663
CHEMBL704	MESALAMINE	4	52,574
CHEMBL772	RESERPINE	4
CHEMBL932	DIPYRIDAMOLE	4
CHEMBL119443	ERGONOVINE	3
CHEMBL1255653	SEPIAPTERIN	3
CHEMBL140	CURCUMIN	3
CHEMBL273862	HYDROXYCAMPTOTHECIN	3
CHEMBL313971	ZUCAPSAICIN	3
CHEMBL413376	SURAMIN HEXASODIUM	3
CHEMBL51483	GOSSYPOL	3
CHEMBL12208	HYMECROMONE	2

PharmGKB: 1 entry (VIP=true, CPIC=false)

PharmGKB variants

3 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs557905	CASP1		0.00	0
rs568910	CASP1		0.00	0
rs580253	CASP1		0.00	0

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: enzyme — C14: Caspase

Most potent curated ligand interactions (4 total), top 4:

Ligand	Action	Affinity	Parameter
VRT-043198	Inhibition	9.1	pKi
pralnacasan	Inhibition	9.0	pKi
uracil 20	Inhibition	8.01	pIC50
M826	Inhibition	7.3	pIC50

Binding affinities (BindingDB)

134 measured of 228 human assays (234 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
(3S)-3-[(2S)-2-[(2S)-2-[(2S)-2-acetamido-3-(4-hydroxyphenyl)propanamido]-3-methylbutanamido]propanamido]-4-oxobutanoic acid	IC50	8.1 nM
(3S)-3-[(2S)-2-[(2S)-2-[(2S)-2-acetamido-3-(4-hydroxyphenyl)propanamido]-3-methylbutanamido]propanamido]-4-oxo-9-phenylnonanoic acid	KI	11 nM
CHEMBL4204225	IC50	16 nM
(3S)-3-({2-[4-(butan-2-yl)-3-methylphenoxy]benzene}sulfonamido)-4-oxobutanoic acid	KI	100 nM
(3S)-3-({2-[3-methyl-4-(propan-2-yl)phenoxy]benzene}sulfonamido)-4-oxobutanoic acid	KI	110 nM
5-{[(4-{[(2S)-1-carboxy-3-oxopropan-2-yl]carbamoyl}phenyl)methyl]sulfamoyl}-2-hydroxybenzoic acid	KI	160 nM
U83836E (B8)	IC50	167 nM
U74389G (B9)	IC50	174 nM
(4S)-4-{[(1S)-1-{[(2S)-1-carboxy-3-oxopropan-2-yl]carbamoyl}-2-methylpropyl]carbamoyl}-4-[(3S)-3-acetamido-3-formamidopropanoic acid]butanoic acid	IC50	190 nM
(3S)-4-oxo-3-{[2-(4-phenylphenoxy)benzene]sulfonamido}butanoic acid	KI	290 nM
(3S)-4-oxo-3-({2-[3-(propan-2-yl)phenoxy]benzene}sulfonamido)butanoic acid	KI	410 nM
(3S)-3-{[2-(3-methylphenoxy)benzene]sulfonamido}-4-oxobutanoic acid	KI	430 nM
(3S)-4-oxo-3-({2-[4-(pentan-3-yl)phenoxy]benzene}sulfonamido)butanoic acid	KI	440 nM
(3S)-4-oxo-3-{[2-(3,4,5-trimethylphenoxy)benzene]sulfonamido}butanoic acid	KI	450 nM
(3S)-3-({2-[4-(butan-2-yl)phenoxy]benzene}sulfonamido)-4-oxobutanoic acid	KI	490 nM
(4S)-5-[[(2S)-1-[[(E,2S)-1-carboxy-4-methylsulfonylbut-3-en-2-yl]amino]-3-methyl-1-oxobutan-2-yl]amino]-4-[[(2S)-3-(4-hydroxyphenyl)-2-(phenylmethoxycarbonylamino)propanoyl]amino]-5-oxopentanoic acid	IC50	500 nM	US-9045524: Selective caspase inhibitors and uses thereof
(3S)-4-oxo-3-({2-[4-(propan-2-yl)phenoxy]benzene}sulfonamido)butanoic acid	KI	620 nM
(3S)-5-(benzylsulfanyl)-3-[(2S)-2-[2-hydroxy-2-(5-iodo-2-methoxyphenyl)acetamido]-3-methylbutanamido]-4-oxopentanoic acid	IC50	675 nM
(E,3S)-3-[[(2S)-2-[[(2S)-2-[[(2S)-3-carboxy-2-(phenylmethoxycarbonylamino)propanoyl]amino]-3-(1H-indol-3-yl)propanoyl]amino]-3-methylbutanoyl]amino]-5-methylsulfonylpent-4-enoic acid	IC50	700 nM	US-9045524: Selective caspase inhibitors and uses thereof
(3S)-5-(benzylsulfanyl)-3-[(2S)-2-[(3,5-dibromophenyl)formamido]-3-methylbutanamido]-4-oxopentanoic acid	IC50	860 nM
(3S)-3-{[2-(4-cyclopentylphenoxy)benzene]sulfonamido}-4-oxobutanoic acid	KI	880 nM
(3S)-3-{[2-(4-cyclohexylphenoxy)benzene]sulfonamido}-4-oxobutanoic acid	KI	900 nM
(E,3S)-3-[[(2S)-2-[[(2S)-2-[[(2S)-3-carboxy-2-(phenylmethoxycarbonylamino)propanoyl]amino]-2-(2,3-dihydro-1H-inden-2-yl)acetyl]amino]-3-methylbutanoyl]amino]-5-methylsulfonylpent-4-enoic acid	IC50	900 nM	US-9045524: Selective caspase inhibitors and uses thereof
(3S)-3-{[2-(2,3-dimethylphenoxy)benzene]sulfonamido}-4-oxobutanoic acid	KI	1000 nM
(3S)-5-(benzylsulfanyl)-3-[(2S)-2-[(2R)-2-(5-bromo-2-methoxyphenyl)pent-4-ynamido]-3-methylbutanamido]-4-oxopentanoic acid	IC50	1030 nM
(3S)-3-{[2-(4-methylphenoxy)benzene]sulfonamido}-4-oxobutanoic acid	KI	1100 nM
(E,3S)-3-[[(2S)-2-[[(2S)-2-[[(2S)-3-carboxy-2-(phenylmethoxycarbonylamino)propanoyl]amino]-3-quinolin-2-ylpropanoyl]amino]-3-methylbutanoyl]amino]-5-phenoxysulfonylpent-4-enoic acid	IC50	1200 nM	US-9045524: Selective caspase inhibitors and uses thereof
(E,3S)-5-(benzenesulfonyl)-3-[[(2S)-2-[[(2S)-2-[[(2S)-3-(4-hydroxyphenyl)-2-(phenylmethoxycarbonylamino)propanoyl]amino]-3-methylbutanoyl]amino]propanoyl]amino]pent-4-enoic acid	IC50	1300 nM	US-9045524: Selective caspase inhibitors and uses thereof
(4S)-5-[[(2S)-1-[[(E,2S)-1-carboxy-4-methylsulfonylbut-3-en-2-yl]amino]-3-methyl-1-oxobutan-2-yl]amino]-4-[[(2S)-3-carboxy-2-(phenylmethoxycarbonylamino)propanoyl]amino]-5-oxopentanoic acid	IC50	1400 nM	US-9045524: Selective caspase inhibitors and uses thereof
(S)-5-({5-[1-Carboxymethyl-3-(2-chloro-benzylsulfanyl)-2-oxo-propylcarbamoyl]pyridin-2-ylmethyl}sulfamoyl)-2-hydroxy-benzoic Acid	KI	1500 nM
CHEMBL1223107	KI	1500 nM
(3S)-5-(benzylsulfanyl)-3-[(2S)-2-[2-(5-bromo-2-methoxyphenyl)-2-hydroxyacetamido]-3-methylbutanamido]-4-oxopentanoic acid	IC50	1540 nM
(3S)-5-{[(2-chloro-6-fluorophenyl)methyl]sulfanyl}-3-[(2S)-2-[1-(5-methanesulfonyl-2-methoxyphenyl)acetamido]-3-methylbutanamido]-4-oxopentanoic acid	IC50	1600 nM
(3S)-4-oxo-3-[(2-phenylbenzene)sulfonamido]butanoic acid	KI	1600 nM
(3S)-3-[(2S)-2-[(2S)-2-[(3S)-3-formamido-3-(phenylformamido)propanoic acid]propanamido]-3-methylbutanamido]-4-oxo-7-phenylheptanoic acid	IC50	1650 nM
Compound 3	IC50	1800 nM
(3S)-5-[(cyclohexylmethyl)sulfanyl]-3-[(2S)-2-[1-(2,5-dimethoxyphenyl)acetamido]-3-methylbutanamido]-4-oxopentanoic acid	IC50	1800 nM
1-[3-(4-chlorophenyl)-5-[(4-fluorobenzyl)amino]-1,2,4-triazol-1-yl]-2-methoxy-ethanone	IC50	1800 nM
(S)-3-(6-Methyl-biphenyl-2-sulfonylamino)-4-oxo-butyric acid	KI	1900 nM
Thiophene Scaffold 66a	KI	1900 nM
(E,3S)-3-[[(2S)-2-[[(2S)-2-[[(2S)-3-carboxy-2-(phenylmethoxycarbonylamino)propanoyl]amino]-2-phenylacetyl]amino]-3-methylbutanoyl]amino]-5-methylsulfonylpent-4-enoic acid	IC50	2000 nM	US-9045524: Selective caspase inhibitors and uses thereof
(S)-3-(3-Acetylamino-biphenyl-2-sulfonylamino)-4-oxo-butyric acid	KI	2300 nM
(3S)-4-oxo-3-[(2-phenoxybenzene)sulfonamido]butanoic acid	KI	2400 nM
(3S)-5-(benzylsulfanyl)-3-[(2S)-2-{2-hydroxy-2-[2-methoxy-5-(3-methyl-1,2,4-oxadiazol-5-yl)phenyl]acetamido}-3-methylbutanamido]-4-oxopentanoic acid	IC50	2460 nM
7-[8-formyl-1,6,7-trihydroxy-3-methyl-5-(propan-2-yl)naphthalen-2-yl]-2,3,8-trihydroxy-6-methyl-4-(propan-2-yl)naphthalene-1-carbaldehyde	IC50	2550 nM
(3S)-5-(benzylsulfanyl)-3-[(2S)-2-[(5-fluoro-1H-indol-2-yl)formamido]-3-methylbutanamido]-4-oxopentanoic acid	IC50	2600 nM
(3S)-3-[(2S)-2-[1-(2,5-dimethoxyphenyl)acetamido]-3-methylbutanamido]-5-[(2-methylpropyl)sulfanyl]-4-oxopentanoic acid	IC50	2600 nM
Heterocyclic deriv. 69b	KI	2700 nM
N-(4-acetylphenyl)-N’-(4-chlorophenyl)urea	IC50	2980 nM
(3S)-3-{[2-(2-methylphenoxy)benzene]sulfonamido}-4-oxobutanoic acid	KI	3000 nM

ChEMBL bioactivities

1605 potent at pChembl≥5 of 3884 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
9.96	IC50	0.11	nM	CHEMBL267338
9.82	Ki	0.15	nM	CHEMBL286519
9.82	Ki	0.15	nM	CHEMBL26544
9.70	IC50	0.2	nM	CHEMBL589552
9.70	Ki	0.2	nM	CHEMBL553107
9.43	Ki	0.37	nM	CHEMBL115090
9.43	IC50	0.37	nM	CHEMBL111965
9.40	IC50	0.4	nM	CHEMBL112207
9.24	Ki	0.58	nM	CHEMBL1221597
9.22	Ki	0.6	nM	VRT-18858
9.15	Ki	0.7	nM	CHEMBL37630
9.12	Ki	0.76	nM	CHEMBL366456
9.12	IC50	0.76	nM	CHEMBL111839
9.12	Ki	0.76	nM	CHEMBL37630
9.10	Ki	0.8	nM	VRT 043198
9.07	Ki	0.85	nM	CHEMBL366534
9.05	Ki	0.9	nM	CHEMBL1221644
9.02	Ki	0.95	nM	CHEMBL1221595
9.00	IC50	1	nM	CHEMBL199492
9.00	IC50	1	nM	CHEMBL381667
9.00	IC50	1	nM	CHEMBL198516
9.00	IC50	1	nM	CHEMBL382090
9.00	IC50	1	nM	CHEMBL372189
9.00	IC50	1	nM	CHEMBL196761
9.00	IC50	1	nM	CHEMBL197811
9.00	IC50	1	nM	CHEMBL196911
9.00	IC50	1	nM	CHEMBL198644
9.00	IC50	1	nM	CHEMBL196753
9.00	IC50	1	nM	CHEMBL198845
9.00	IC50	1	nM	CHEMBL381624
9.00	IC50	1	nM	CHEMBL394351
9.00	IC50	1	nM	CHEMBL268772
9.00	IC50	1	nM	CHEMBL411178
9.00	IC50	1	nM	CHEMBL3142900
9.00	Ki	1	nM	CHEMBL1223110
9.00	Ki	1	nM	CHEMBL1223114
9.00	Ki	1	nM	CHEMBL299288
9.00	Ki	1	nM	CHEMBL293979
8.96	Ki	1.1	nM	CHEMBL2371932
8.94	Ki	1.15	nM	CHEMBL368313
8.90	Ki	1.26	nM	CHEMBL1221691
8.89	IC50	1.3	nM	VRT-18858
8.89	IC50	1.3	nM	CHEMBL5569363
8.89	Ki	1.29	nM	CHEMBL1221643
8.89	Ki	1.3	nM	CHEMBL25943
8.88	Ki	1.31	nM	CHEMBL1221743
8.85	Ki	1.4	nM	CHEMBL25925
8.82	Ki	1.5	nM	CHEMBL287440
8.77	IC50	1.7	nM	CHEMBL115952
8.75	Ki	1.79	nM	CHEMBL176584

PubChem BioAssay actives

764 with measured affinity, of 1554 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
(4S)-4-[[(2S)-2-acetamido-3-(4-hydroxyphenyl)propanoyl]amino]-5-[[(2S)-1-[[1-carboxy-4-[(7,7-dihydroxy-2-oxo-1-bicyclo[2.2.1]heptanyl)methylsulfonylamino]-3-oxobutan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]amino]-5-oxopentanoic acid	49353: Compound was evaluated for the inhibitory activity against caspase-1	ic50	0.0001	uM
(3S)-3-[[(2S)-2-[[(2S)-3-methyl-2-(naphthalene-2-carbonylamino)butanoyl]amino]propanoyl]amino]-4-oxobutanoic acid	462661: Inhibition of human recombinant caspase 1	ic50	0.0002	uM
3-[[(2S)-2-[3-(naphthalene-2-carbonylamino)-2-oxo-1-pyridinyl]butanoyl]amino]-4-oxo-5-(2-phenylethylamino)pentanoic acid	49353: Compound was evaluated for the inhibitory activity against caspase-1	ic50	0.0004	uM
5-[(7,7-dimethyl-2-oxo-1-bicyclo[2.2.1]heptanyl)methylsulfonylamino]-3-[[(2S)-4-[2-(1-methylindol-3-yl)ethylamino]-4-oxo-2-propan-2-ylbutanoyl]amino]-4-oxopentanoic acid	49353: Compound was evaluated for the inhibitory activity against caspase-1	ic50	0.0004	uM
(3S)-3-[2-[3-(naphthalene-2-carbonylamino)-2-oxo-1-pyridinyl]butanoylamino]-4-oxo-5-(2-phenylethylamino)pentanoic acid	2100632: Binding affinity to caspase-1 (unknown origin) assessed as inhibition constant	ki	0.0004	uM
(3S)-3-[[(2S)-4-(2-naphthalen-1-ylethylamino)-4-oxo-2-propan-2-ylbutanoyl]amino]-4-oxobutanoic acid	501505: Inhibition of human ICE	ki	0.0006	uM
(3S)-3-[[(4S,7S)-7-(isoquinoline-1-carbonylamino)-6,10-dioxo-2,3,4,7,8,9-hexahydro-1H-pyridazino[1,2-a]diazepine-4-carbonyl]amino]-4-oxobutanoic acid	501505: Inhibition of human ICE	ki	0.0006	uM
(3S)-3-[[(2S)-2-[[(2S)-2-[[(2S)-2-acetamido-3-(4-hydroxyphenyl)propanoyl]amino]-3-methylbutanoyl]amino]propanoyl]amino]-4-oxobutanoic acid	501505: Inhibition of human ICE	ki	0.0007	uM
(3S)-3-[[(2S)-1-[(2S)-2-[(4-amino-3-chlorobenzoyl)amino]-3,3-dimethylbutanoyl]pyrrolidine-2-carbonyl]amino]-4-oxobutanoic acid	1899353: Inhibition of caspase 1 (unknown origin)	ki	0.0008	uM
3-[[(2S)-2-[[(2S)-2-[[(2S)-2-acetamido-3-(4-hydroxyphenyl)propanoyl]amino]-3-methylbutanoyl]amino]propanoyl]amino]-4-oxobutanoic acid	49354: Dissociation constant for inhibition of caspase-1	ic50	0.0008	uM
(3S)-5-(butylamino)-3-[2-[3-(naphthalene-2-carbonylamino)-2-oxo-1-pyridinyl]butanoylamino]-4-oxopentanoic acid	2100632: Binding affinity to caspase-1 (unknown origin) assessed as inhibition constant	ki	0.0008	uM
(3S)-5-(hexylamino)-3-[2-[3-(naphthalene-2-carbonylamino)-2-oxo-1-pyridinyl]butanoylamino]-4-oxopentanoic acid	2100632: Binding affinity to caspase-1 (unknown origin) assessed as inhibition constant	ki	0.0008	uM
(3S)-3-[[(2S)-4-[2-(3-chloroanilino)ethylamino]-4-oxo-2-propan-2-ylbutanoyl]amino]-4-oxobutanoic acid	501505: Inhibition of human ICE	ki	0.0009	uM
(3S)-3-[[(2S)-4-[2-(1,2-dimethylindol-3-yl)ethylamino]-4-oxo-2-propan-2-ylbutanoyl]amino]-4-oxobutanoic acid	501505: Inhibition of human ICE	ki	0.0009	uM
(3S)-3-[[(4S,7S)-7-[[4-(carboxymethoxy)benzoyl]amino]-6,10-dioxo-2,3,4,7,8,9-hexahydro-1H-pyridazino[1,2-a]diazepine-4-carbonyl]amino]-4-oxobutanoic acid	93790: Reversible Inhibition constants against IL-1 beta converting enzyme (ICE)	ki	0.0010	uM
benzyl (4S,7S,9Z,11aS)-4-[[(3S)-2-hydroxy-5-oxooxolan-3-yl]carbamoyl]-7-(isoquinoline-1-carbonylamino)-6-oxo-3,4,7,8,11,11a-hexahydro-1H-pyrazino[1,2-a]azocine-2-carboxylate	257627: Inhibitory activity against Caspase 1	ic50	0.0010	uM
(4S,7S,11aS)-N-[(3S)-2-hydroxy-5-oxooxolan-3-yl]-7-(naphthalene-2-carbonylamino)-6-oxo-1,2,3,4,7,8,9,10,11,11a-decahydropyrazino[1,2-a]azocine-4-carboxamide	257627: Inhibitory activity against Caspase 1	ic50	0.0010	uM
(3S)-3-[[(4S,7S)-7-[(2-fluorobenzoyl)amino]-6,10-dioxo-2,3,4,7,8,9-hexahydro-1H-pyridazino[1,2-a]diazepine-4-carbonyl]amino]-4-oxobutanoic acid	93790: Reversible Inhibition constants against IL-1 beta converting enzyme (ICE)	ki	0.0010	uM
(4S,7S,11aS)-N-[(3S)-2-hydroxy-5-oxooxolan-3-yl]-7-(naphthalene-2-carbonylamino)-6-oxo-3,4,7,8,9,10,11,11a-octahydro-1H-[1,4]oxazino[4,3-a]azocine-4-carboxamide	257627: Inhibitory activity against Caspase 1	ic50	0.0010	uM
(4S,7S,11aS)-N-[(3S)-2-hydroxy-5-oxooxolan-3-yl]-7-(isoquinoline-1-carbonylamino)-6-oxo-3,4,7,8,9,10,11,11a-octahydro-1H-[1,4]oxazino[4,3-a]azocine-4-carboxamide	257627: Inhibitory activity against Caspase 1	ic50	0.0010	uM
benzyl (4S,7S,9Z,11aS)-7-benzamido-4-[[(3S)-2-hydroxy-5-oxooxolan-3-yl]carbamoyl]-6-oxo-3,4,7,8,11,11a-hexahydro-1H-pyrazino[1,2-a]azocine-2-carboxylate	257627: Inhibitory activity against Caspase 1	ic50	0.0010	uM
(4S,7S,11aS)-2-(benzenesulfonyl)-N-[(3S)-2-hydroxy-5-oxooxolan-3-yl]-7-(isoquinoline-1-carbonylamino)-6-oxo-3,4,7,8,9,10,11,11a-octahydro-1H-pyrazino[1,2-a]azocine-4-carboxamide	257627: Inhibitory activity against Caspase 1	ic50	0.0010	uM
(4S,7S,11aS)-N-[(3S)-2-hydroxy-5-oxooxolan-3-yl]-7-(isoquinoline-1-carbonylamino)-2-methylsulfonyl-6-oxo-3,4,7,8,9,10,11,11a-octahydro-1H-pyrazino[1,2-a]azocine-4-carboxamide	257627: Inhibitory activity against Caspase 1	ic50	0.0010	uM
(4S,7S,11aS)-7-(1-benzothiophene-2-carbonylamino)-N-[(3S)-2-hydroxy-5-oxooxolan-3-yl]-6-oxo-3,4,7,8,9,10,11,11a-octahydro-1H-[1,4]oxazino[4,3-a]azocine-4-carboxamide	257627: Inhibitory activity against Caspase 1	ic50	0.0010	uM
(4S,7S,11aS)-2-(benzenesulfonyl)-N-[(3S)-2-hydroxy-5-oxooxolan-3-yl]-7-(naphthalene-2-carbonylamino)-6-oxo-3,4,7,8,9,10,11,11a-octahydro-1H-pyrazino[1,2-a]azocine-4-carboxamide	257627: Inhibitory activity against Caspase 1	ic50	0.0010	uM
benzyl (4S,7S,9Z,11aS)-4-[[(3S)-2-hydroxy-5-oxooxolan-3-yl]carbamoyl]-7-(naphthalene-2-carbonylamino)-6-oxo-3,4,7,8,11,11a-hexahydro-1H-pyrazino[1,2-a]azocine-2-carboxylate	257627: Inhibitory activity against Caspase 1	ic50	0.0010	uM
(4S,7S,11aS)-N-[(3S)-2-hydroxy-5-oxooxolan-3-yl]-7-(isoquinoline-1-carbonylamino)-6-oxo-1,2,3,4,7,8,9,10,11,11a-decahydropyrazino[1,2-a]azocine-4-carboxamide	257627: Inhibitory activity against Caspase 1	ic50	0.0010	uM
(4S,7S,11aS)-N-[(3S)-2-hydroxy-5-oxooxolan-3-yl]-2-methylsulfonyl-7-(naphthalene-2-carbonylamino)-6-oxo-3,4,7,8,9,10,11,11a-octahydro-1H-pyrazino[1,2-a]azocine-4-carboxamide	257627: Inhibitory activity against Caspase 1	ic50	0.0010	uM
N-[(6S)-1-[(2S)-1-[[(3S)-2-hydroxy-5-oxooxolan-3-yl]amino]-1-oxopropan-2-yl]-7-oxo-5,6-dihydro-2H-azepin-6-yl]naphthalene-2-carboxamide	293084: Inhibition of ICE	ic50	0.0010	uM
N-[(6S)-1-[2-[[(3S)-2-hydroxy-5-oxooxolan-3-yl]amino]-2-oxoethyl]-3-[[(3-methoxybenzoyl)amino]methyl]-7-oxo-5,6-dihydro-2H-azepin-6-yl]naphthalene-2-carboxamide	293084: Inhibition of ICE	ic50	0.0010	uM
N-[(6S)-1-[2-[[(3S)-2-hydroxy-5-oxooxolan-3-yl]amino]-2-oxoethyl]-3-[[(4-methoxybenzoyl)amino]methyl]-7-oxo-5,6-dihydro-2H-azepin-6-yl]naphthalene-2-carboxamide	293084: Inhibition of ICE	ic50	0.0010	uM
(3S)-5-(3,3-diphenylpropanoyloxy)-3-[[(2S)-2-[[(2S)-3-methyl-2-(phenylmethoxycarbonylamino)butanoyl]amino]propanoyl]amino]-4-oxopentanoic acid	501891: Inhibition of ICE	ki	0.0010	uM
(3S)-5-[[(3aS,7aS)-2-oxo-3a,4,5,6,7,7a-hexahydro-3H-indol-1-yl]oxy]-3-[[(2S)-2-[[(2S)-3-methyl-2-(phenylmethoxycarbonylamino)butanoyl]amino]propanoyl]amino]-4-oxopentanoic acid	501891: Inhibition of ICE	ki	0.0010	uM
(3S)-3-[[(7S)-7-[(2-fluorobenzoyl)amino]-6,10-dioxo-2,3,4,7,8,9-hexahydro-1H-pyridazino[1,2-a]diazepine-4-carbonyl]amino]-4-oxobutanoic acid	49354: Dissociation constant for inhibition of caspase-1	ic50	0.0010	uM
(3S)-3-[2-[3-(naphthalene-2-carbonylamino)-2-oxo-1-pyridinyl]butanoylamino]-4-oxo-5-(3-phenylpropylamino)pentanoic acid	2100632: Binding affinity to caspase-1 (unknown origin) assessed as inhibition constant	ki	0.0011	uM
(4S,7S)-N-[(2R,3S)-2-hydroxy-5-oxooxolan-3-yl]-7-(isoquinoline-1-carbonylamino)-6,10-dioxo-2,3,4,7,8,9-hexahydro-1H-pyridazino[1,2-a]diazepine-4-carboxamide	2100624: Inhibition of caspase-1 (unknown origin) by fluorescence based analysis	ic50	0.0013	uM
(3S)-3-[[2-[3-(naphthalene-2-carbonylamino)-2-oxo-1-pyridinyl]-2-phenylacetyl]amino]-4-oxo-5-phenoxypentanoic acid	93791: The binding affinity against IL-1 beta converting enzyme	ki	0.0013	uM
(3S)-3-[[(2S)-4-[2-(2-methyl-1H-indol-3-yl)ethylamino]-4-oxo-2-propan-2-ylbutanoyl]amino]-4-oxobutanoic acid	501505: Inhibition of human ICE	ki	0.0013	uM
(3S)-4-oxo-3-[[(2S)-4-oxo-2-propan-2-yl-4-[2-(2,5,6-trimethylbenzimidazol-1-yl)ethylamino]butanoyl]amino]butanoic acid	501505: Inhibition of human ICE	ki	0.0013	uM
(3S)-4-oxo-3-[[(2S)-4-oxo-2-propan-2-yl-4-(2-quinolin-4-ylethylamino)butanoyl]amino]butanoic acid	501505: Inhibition of human ICE	ki	0.0013	uM
5-(3-carbamoylnaphthalen-2-yl)oxy-3-[[(2S)-2-[[(2S)-3-methyl-2-(phenylmethoxycarbonylamino)butanoyl]amino]propanoyl]amino]-4-oxopentanoic acid	49353: Compound was evaluated for the inhibitory activity against caspase-1	ic50	0.0017	uM
(3S)-5-[hexyl(methyl)amino]-3-[2-[3-(naphthalene-2-carbonylamino)-2-oxo-1-pyridinyl]butanoylamino]-4-oxopentanoic acid	2100632: Binding affinity to caspase-1 (unknown origin) assessed as inhibition constant	ki	0.0018	uM
(3S)-4-oxo-3-[[(2S)-4-oxo-2-propan-2-yl-4-(2-quinolin-5-ylethylamino)butanoyl]amino]butanoic acid	501505: Inhibition of human ICE	ki	0.0018	uM
3-[[(2S)-2-[[(2S)-3-methyl-2-(phenylmethoxycarbonylamino)butanoyl]amino]propanoyl]amino]-4-oxo-5-(3-phenylpropanoyloxy)pentanoic acid	49353: Compound was evaluated for the inhibitory activity against caspase-1	ic50	0.0019	uM
(4S,7S)-N-[(2R,3S)-2-ethoxy-5-oxooxolan-3-yl]-7-(isoquinoline-1-carbonylamino)-6,10-dioxo-2,3,4,7,8,9-hexahydro-1H-pyridazino[1,2-a]diazepine-4-carboxamide	254996: Inhibition of caspase-1 using fluorogenic substrate and BMG Fluostar plate reader for 30 min at 37 degree C	ic50	0.0020	uM
3-[[(2S)-1-[(2S)-2-[[(2S)-2-acetamido-3-(4-hydroxyphenyl)propanoyl]amino]-3-methylbutanoyl]-4-hydroxypyrrolidine-2-carbonyl]amino]-4-oxobutanoic acid	49354: Dissociation constant for inhibition of caspase-1	ic50	0.0020	uM
3-[[2-[[(2S)-2-benzamido-3-methylbutanoyl]-(2,3-dihydro-1H-inden-2-yl)amino]acetyl]amino]-4-(1,3-benzoxazol-2-yl)-4-oxobutanoic acid	49353: Compound was evaluated for the inhibitory activity against caspase-1	ic50	0.0020	uM
(4S,7S,11aS)-7-benzamido-2-(benzenesulfonyl)-N-[(3S)-2-hydroxy-5-oxooxolan-3-yl]-6-oxo-3,4,7,8,9,10,11,11a-octahydro-1H-pyrazino[1,2-a]azocine-4-carboxamide	257627: Inhibitory activity against Caspase 1	ic50	0.0020	uM
N-[(6S)-3-(benzamidomethyl)-1-[2-[[(3S)-2-hydroxy-5-oxooxolan-3-yl]amino]-2-oxoethyl]-7-oxo-5,6-dihydro-2H-azepin-6-yl]naphthalene-2-carboxamide	293084: Inhibition of ICE	ic50	0.0020	uM
N-[(6S)-1-[2-[[(3S)-2-hydroxy-5-oxooxolan-3-yl]amino]-2-oxoethyl]-3-[[(2-methoxybenzoyl)amino]methyl]-7-oxo-5,6-dihydro-2H-azepin-6-yl]naphthalene-2-carboxamide	293084: Inhibition of ICE	ic50	0.0020	uM

CTD chemical–gene interactions

301 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Lipopolysaccharides	increases reaction, affects expression, affects reaction, decreases reaction, increases activity (+6 more)	24
Acetylcysteine	affects reaction, increases cleavage, decreases expression, increases expression, increases abundance (+5 more)	23
Adenosine Triphosphate	affects cotreatment, decreases reaction, increases expression, increases cleavage, increases activity (+2 more)	15
N-(1,2,3,5,6,7-hexahydro-S-indacen-4-ylcarbamoyl)-4-(2-hydroxy-2-propanyl)-2-furansulfonamide	affects cotreatment, affects reaction, increases cleavage, decreases reaction, increases expression (+1 more)	9
Cadmium Chloride	decreases reaction, increases abundance, increases expression, affects cotreatment, increases cleavage (+2 more)	9
Glucose	increases expression, affects cotreatment, increases cleavage, affects reaction, increases reaction (+1 more)	7
Silicon Dioxide	affects cotreatment, affects reaction, decreases reaction, affects localization, affects expression (+4 more)	7
Particulate Matter	increases abundance, increases cleavage, increases expression, decreases expression, affects reaction (+1 more)	7
bisphenol A	increases expression, affects expression, decreases reaction, decreases expression, increases activity	6
Resveratrol	decreases reaction, increases secretion, increases abundance, increases cleavage, decreases activity (+5 more)	6
Tetradecanoylphorbol Acetate	increases activity, affects activity, decreases reaction, increases cleavage, increases secretion (+4 more)	6
lipopolysaccharide, Escherichia coli O111 B4	affects cotreatment, decreases reaction, increases cleavage, increases activity, affects reaction (+1 more)	5
Arsenic Trioxide	increases activity, increases expression, increases reaction, affects cotreatment, decreases reaction (+1 more)	5
Cadmium	increases abundance, increases expression, increases cleavage, decreases expression, affects reaction (+1 more)	5
Uric Acid	increases secretion, affects reaction, affects cotreatment, increases phosphorylation, decreases reaction (+2 more)	5
Asbestos, Crocidolite	increases secretion, affects reaction, decreases reaction, increases expression, increases activity (+1 more)	5
sodium arsenite	increases cleavage, increases expression, increases reaction, decreases reaction, increases abundance (+1 more)	4
3-methyladenine	increases reaction, affects cotreatment, decreases reaction, increases cleavage, increases expression	4
L 709049	decreases reaction, increases expression, increases secretion, decreases activity	4
MitoTEMPO	affects cotreatment, decreases reaction, increases cleavage, increases expression, increases secretion	4
Acrolein	increases cleavage, increases reaction, increases expression, decreases reaction, increases oxidation (+3 more)	4
Air Pollutants	affects cotreatment, increases abundance, increases oxidation, decreases expression, increases expression	4
Nickel	increases abundance, increases cleavage, decreases expression, increases expression, decreases reaction	4
Quercetin	decreases reaction, increases expression, increases reaction, decreases expression	4
Tretinoin	increases expression, increases reaction, increases cleavage	4
N-acetyl-tyrosyl-valyl-alanyl-aspartyl chloromethyl ketone	decreases reaction, increases activity, decreases activity	3
tyrosyl-valyl-alanyl-aspartic acid fluoromethyl ketone	decreases reaction, increases expression, affects cotreatment, increases cleavage, decreases cleavage	3
lipopolysaccharide, E coli O55-B5	increases expression, affects cotreatment, increases cleavage, decreases reaction, affects activity (+2 more)	3
Calcimycin	affects cotreatment, increases activity, decreases reaction, increases cleavage	3
Zoledronic Acid	affects expression, affects cotreatment, increases expression	3

ChEMBL screening assays

216 unique, capped per target: 203 binding, 13 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4199992	Binding	Activation of caspase (unknown origin)	MK-8353: Discovery of an Orally Bioavailable Dual Mechanism ERK Inhibitor for Oncology. — ACS Med Chem Lett
CHEMBL1613851	Functional	PUBCHEM_BIOASSAY: Concentration-Response Counterscreen for Redox Active Inhibitors of Caspase-1: Cysteine. (Class of assay: confirmatory)	PubChem BioAssay data set

Cellosaurus cell lines

4 cell lines: 3 cancer cell line, 1 transformed cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_5I76	THP1-defCASP1	Cancer cell line	Male
CVCL_B1A8	Abcam THP-1 CASP1 KO	Cancer cell line	Male
CVCL_B2TI	Abcam HEK293T CASP1 KO	Transformed cell line	Female
CVCL_D6CN	HyCyte THP-1 KO-hCASP1	Cancer cell line	Male

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.