CASP7

Summary

CASP7 (caspase 7, HGNC:1508) is a protein-coding gene on chromosome 10q25.3, encoding Caspase-7 (P55210). Thiol protease involved in different programmed cell death processes, such as apoptosis, pyroptosis or granzyme-mediated programmed cell death, by proteolytically cleaving target proteins.

This gene encodes 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 two subunits, large and small, that dimerize to form the active enzyme. The precursor of the encoded protein is cleaved by caspase 3 and 10, is activated upon cell death stimuli and induces apoptosis. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene.

Source: NCBI Gene 840 — RefSeq curated summary.

At a glance

• GWAS associations: 4
• Clinical variants (ClinVar): 66 total
• Druggable target: yes — 32 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_001227

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:1508
Approved symbol	CASP7
Name	caspase 7
Location	10q25.3
Locus type	gene with protein product
Status	Approved
Aliases	MCH3, CMH-1, ICE-LAP3
Ensembl gene	ENSG00000165806
Ensembl biotype	protein_coding
OMIM	601761
Entrez	840

Gene structure

Transcript identifiers

Ensembl transcripts: 25 — 23 protein_coding, 1 protein_coding_CDS_not_defined, 1 retained_intron

ENST00000345633, ENST00000369315, ENST00000369318, ENST00000369321, ENST00000369331, ENST00000429617, ENST00000452490, ENST00000468790, ENST00000487232, ENST00000614447, ENST00000621345, ENST00000621607, ENST00000672138, ENST00000891217, ENST00000891218, ENST00000891219, ENST00000891220, ENST00000891221, ENST00000891222, ENST00000891223, ENST00000891224, ENST00000891225, ENST00000959920, ENST00000959921, ENST00000959922

RefSeq mRNA: 8 — MANE Select: NM_001227 NM_001227, NM_001267056, NM_001267057, NM_001267058, NM_001320911, NM_033338, NM_033339, NM_033340

CCDS: CCDS58096, CCDS73200, CCDS7580, CCDS7581, CCDS7582

Canonical transcript exons

ENST00000369318 — 7 exons

Exon	Start	End
ENSE00000000111	113729311	113730905
ENSE00001832746	113679912	113679978
ENSE00003494172	113726305	113726434
ENSE00003505017	113721032	113721168
ENSE00003512533	113697494	113697603
ENSE00003542525	113725362	113725537
ENSE00003555462	113721651	113721779

Expression profiles

Bgee: expression breadth ubiquitous, 269 present calls, max score 96.19.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 19.8104 / max 169.7284, expressed in 1770 samples.

FANTOM5 promoters (9 alternative TSS)

Promoter ID	TPM avg	Samples expressed
107131	10.4919	1705
107130	3.6008	1524
107126	3.5303	1480
107127	0.9458	617
107129	0.7040	383
107128	0.1796	55
107132	0.1562	57
107135	0.1326	41
107134	0.0691	32

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
rectum	UBERON:0001052	96.19	gold quality
palpebral conjunctiva	UBERON:0001812	96.02	gold quality
epithelium of nasopharynx	UBERON:0001951	95.73	gold quality
jejunal mucosa	UBERON:0000399	95.69	gold quality
mucosa of transverse colon	UBERON:0004991	95.60	gold quality
colonic mucosa	UBERON:0000317	95.00	gold quality
duodenum	UBERON:0002114	94.49	gold quality
parotid gland	UBERON:0001831	94.26	gold quality
nasal cavity epithelium	UBERON:0005384	94.09	gold quality
mucosa of sigmoid colon	UBERON:0004993	94.06	gold quality
nasal cavity mucosa	UBERON:0001826	93.63	gold quality
transverse colon	UBERON:0001157	93.06	gold quality
mucosa of paranasal sinus	UBERON:0005030	92.96	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	92.22	gold quality
small intestine	UBERON:0002108	91.27	gold quality
small intestine Peyer’s patch	UBERON:0003454	91.26	gold quality
vermiform appendix	UBERON:0001154	91.02	gold quality
islet of Langerhans	UBERON:0000006	90.91	gold quality
intestine	UBERON:0000160	90.81	gold quality
large intestine	UBERON:0000059	90.70	gold quality
colon	UBERON:0001155	90.45	gold quality
caecum	UBERON:0001153	90.42	gold quality
jejunum	UBERON:0002115	90.25	gold quality
bronchial epithelial cell	CL:0002328	90.12	gold quality
colonic epithelium	UBERON:0000397	90.06	gold quality
germinal epithelium of ovary	UBERON:0001304	90.00	gold quality
epithelium of bronchus	UBERON:0002031	89.91	gold quality
bronchus	UBERON:0002185	89.71	gold quality
body of pancreas	UBERON:0001150	89.64	gold quality
pancreas	UBERON:0001264	89.32	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.05

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CTNNB1, E2F1, IRF1, NFKB, PARP1, RUNX3, SREBF1, SREBF2, TCF7L2, TP53

miRNA regulators (miRDB)

87 targeting CASP7, 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-3134	100.00	66.43	777
HSA-MIR-4776-3P	100.00	68.73	1340
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-507	99.97	70.11	1915
HSA-MIR-9-3P	99.96	70.88	2068
HSA-MIR-557	99.96	70.01	1640
HSA-MIR-146A-5P	99.96	68.93	988
HSA-MIR-146B-5P	99.96	69.13	977
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-23A-3P	99.95	74.24	3163
HSA-MIR-23B-3P	99.95	74.24	3163
HSA-MIR-23C	99.95	73.92	3192
HSA-MIR-7153-5P	99.94	68.89	1006
HSA-MIR-1236-3P	99.94	68.04	1695
HSA-MIR-3143	99.93	71.96	3104
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-552-5P	99.93	68.56	1583
HSA-MIR-7-1-3P	99.91	71.53	4384
HSA-MIR-7-2-3P	99.91	71.40	4394
HSA-MIR-4753-3P	99.90	71.03	3786
HSA-MIR-95-5P	99.89	72.17	3973
HSA-MIR-8062	99.88	68.43	995
HSA-MIR-3065-3P	99.87	70.25	1407
HSA-MIR-3919	99.87	69.45	2489
HSA-MIR-3941	99.86	70.54	2735
HSA-MIR-544A	99.84	68.66	1965

Literature-anchored findings (GeneRIF, showing 40)

• Pro-CASP7 was detected in mitochondria, cytosol, nucleus, and microsomes of U937 cells. During TPA-induced differentiation, it moved to the mitochondria. (PMID:12145703)
• caspase 9 by itself can activate caspase 7 in the absence of the caspase 3-dependent pathway in TNF-alpha-induced apoptosis (PMID:12804035)
• the N-peptide of caspase 7 serves to physically sequester the caspase-7 zymogen in a cytosolic location that prevents access by upstream activators (PMID:12824163)
• our data suggest that the inactivating mutations of the CASPASE-7 gene might lead to the loss of its apoptotic function and contribute to the pathogenesis of some human solid cancers (PMID:12970753)
• caspase-7 is involved earlier than other effector caspases in apoptosis (PMID:14583630)
• caspase 7 and caspase 8, but not caspase 2, are involved in induction of apoptosis by sphingosine (PMID:14584591)
• apoptosis was preceded by proteolytic cleavage of caspases 2, 3, and 7, and wild type STAT1 also induced cleavage of caspase 7 (PMID:14623896)
• Dispensable for the execution of apoptosis in a metastatic melanoma cell line. (PMID:15033720)
• caspase-2, -6 and -7 expression in gastric cancer cells is decreased compared to in normal gastric mucosal cells (PMID:15511269)
• cleavage of Claspin by caspase-7 inactivates the Chk1 signaling pathway (PMID:16123041)
• Caspase 7 activation is a prominent feature in periodontitis-associated tissue injury. (PMID:16213496)
• These results demonstrate that SSRP1 degradation during apoptosis is a two-step process coupling caspase cleavage and ubiquitin-dependent proteolysis. (PMID:16498457)
• Promoters of CASP7 genes are modulated by prohibitin. (PMID:16918502)
• Collectively, these data suggest that cathepsin D activation of caspase 3/7 may be required for inducing one of the death pathways elicited by E. coli. (PMID:17023557)
• AIF overexpression specifically resulted in the activation of caspase-7, thereby amplifying the inhibition of protein synthesis including eIF3g cleavage. (PMID:17094969)
• observation indicates that neither CASP7 nor CASP8 mutation may occur in gastrointestinal lymphomas, and suggests that neither of them may play an important role in the development of gastrointestinal lymphomas (PMID:17532763)
• crystal structures show that the S2 pocket of caspase-7 can accommodate diverse residues (PMID:17697120)
• These findings suggest that caspase-7 facilitates the execution of apoptosis through down-regulation of the 26S proteasome, which regulates the turnover of proteins involved in the apoptotic process. (PMID:17880920)
• These data indicate that cytosolic PDI is a substrate of caspase-3 and -7, and that it has an anti-apoptotic action. (PMID:17978580)
• A reticulon protein is identified as one out of a selected number of caspase targets during apoptosis and as a novel substrate for Cdk1 and 2.[ (PMID:18072206)
• Melatonin maintains mitochondrial membrane potential and attenuates activation of initiator (casp-9) and effector caspases (casp-3/casp-7) and PARP in UVR-exposed HaCaT keratinocytes (PMID:18086147)
• These results revealed that caspase-7 has a novel role during cell cycle progression at mitosis. (PMID:18459962)
• study provides evidence that during T cell proliferation the intracellular caspase inhibitor X-linked inhibitor-of-apoptosis protein (XIAP) interacts with caspases-3/-7, thereby blocking their full activation, substrate cleavage, and cell death (PMID:18521960)
• Valosin-containing protein was cleaved by both capspase-7 and caspase-3 in vitro and during apoptosis; degradomic approach to caspase-7 provides new candidate substrates and valuable clues to the specific function of caspase-7 in apoptosis (PMID:18596415)
• hMTH1 plays an important role in protecting cells against H(2)O(2)-induced apoptosis via a Noxa- and caspase-3/7-mediated signaling pathway, thus conferring a survival advantage through the inhibition of oxidative-stress-induced DNA damage (PMID:18708163)
• CASP7 (caspase 7) rs2227309 SNP was not associated with rheuatoid arthritis (RA) in a European Caucasian population. CASP7 isoforms alpha and beta could have an involvement in the apoptosis process in RA (PMID:18785314)
• During hypoxia in tube-forming endothelial cells, caspase-7 is responsible for chromatin condensation and nuclear fragmentation while caspase-6 is responsible for DNA ladder formation. (PMID:19022247)
• Modulation of effector caspase-7 cleavage determines response of breast and lung tumor cell lines to chemotherapy. (PMID:19241192)
• Results show that caspase 7, as an SREBP-1/2 target, can be induced under mevalonate-restricting conditions, which might help overcome its shortage. (PMID:19323650)
• These findings suggest that genetic variants in caspase-3 and caspase-7 may play a role in endometrial cancer susceptibility. (PMID:19531679)
• Dissecting an allosteric switch in caspase-7 using chemical and mutational probes. (PMID:19581639)
• there is an an association between HCV core and HAX-1, which promotes 5-FU mediated p53-dependent caspase-7 activation and hepatocyte growth inhibition (PMID:19605487)
• the calpain-activated form of caspase-7 has unique enzymatic activity, localization, and binding affinity when compared with the caspase-activated form (PMID:19617626)
• The current study shows that the executioner caspase-3 and -7 have similar conformations for the unliganded active site as well as the inhibitor-bound active site. (PMID:19655253)
• Data show that the N-t-boc-Daidzein induced apoptosis is characterized by caspase activation, XIAP and AKT degradation. (PMID:19738422)
• Specific cleavage by caspase-7 relies on excluding recognition by caspase-3 and not on increasing binding for caspase-7. (PMID:19759058)
• Data show that sorafenib initiated lethal apoptotic process through the release of cytochrome c and caspase 3/7 activation. (PMID:19770576)
• Specifically interfering with caspase-7 activation may hold therapeutic value for the treatment of cancer and inflammatory ailments. (PMID:19782763)
• Results show that wild-type p53 protects cells from caspases dependent death induced by this therapeutic combination in vitro. (PMID:19996278)
• caspase 7 cleavage of ORF57 may represent a cellular function against lytic KSHV infection (PMID:20159985)

Cross-species orthologs

8 orthologs

Organism	Symbol	Gene ID
danio_rerio	casp7	ENSDARG00000091836
mus_musculus	Casp7	ENSMUSG00000025076
rattus_norvegicus	Casp7	ENSRNOG00000056216
drosophila_melanogaster	Dcp-1	FBGN0010501
drosophila_melanogaster	Drice	FBGN0019972
caenorhabditis_elegans		WBGENE00000417
caenorhabditis_elegans		WBGENE00000820
caenorhabditis_elegans	csp-3	WBGENE00000821

Paralogs (16): CASP10 (ENSG00000003400), CFLAR (ENSG00000003402), CASP8 (ENSG00000064012), PYCARD (ENSG00000103490), CASP14 (ENSG00000105141), CASP2 (ENSG00000106144), CASP9 (ENSG00000132906), CASP1 (ENSG00000137752), CASP5 (ENSG00000137757), CASP6 (ENSG00000138794), CASP3 (ENSG00000164305), PYDC1 (ENSG00000169900), CASP4 (ENSG00000196954), CARD16 (ENSG00000204397), CASP12 (ENSG00000204403), CARD18 (ENSG00000255501)

Protein

Protein identifiers

Caspase-7 — P55210 (reviewed: P55210)

Alternative names: Apoptotic protease Mch-3, CMH-1, ICE-like apoptotic protease 3

All UniProt accessions (4): A0A0A0MRL7, A0A5F9ZHZ6, P55210, Q5SVL2

UniProt curated annotations — full annotation on UniProt →

Function. Thiol protease involved in different programmed cell death processes, such as apoptosis, pyroptosis or granzyme-mediated programmed cell death, by proteolytically cleaving target proteins. Has a marked preference for Asp-Glu-Val-Asp (DEVD) consensus sequences, with some plasticity for alternate non-canonical sequences. Its involvement in the different programmed cell death processes is probably determined by upstream proteases that activate CASP7. Acts as an effector caspase involved in the execution phase of apoptosis: following cleavage and activation by initiator caspases (CASP8, CASP9 and/or CASP10), mediates execution of apoptosis by catalyzing cleavage of proteins, such as CLSPN, PARP1, PTGES3 and YY1. Compared to CASP3, acts as a minor executioner caspase and cleaves a limited set of target proteins. Acts as a key regulator of the inflammatory response in response to bacterial infection by catalyzing cleavage and activation of the sphingomyelin phosphodiesterase SMPD1 in the extracellular milieu, thereby promoting membrane repair. Regulates pyroptosis in intestinal epithelial cells: cleaved and activated by CASP1 in response to S.typhimurium infection, promoting its secretion to the extracellular milieu, where it catalyzes activation of SMPD1, generating ceramides that repair membranes and counteract the action of gasdermin-D (GSDMD) pores. Regulates granzyme-mediated programmed cell death in hepatocytes: cleaved and activated by granzyme B (GZMB) in response to bacterial infection, promoting its secretion to the extracellular milieu, where it catalyzes activation of SMPD1, generating ceramides that repair membranes and counteract the action of perforin (PRF1) pores. Following cleavage by CASP1 in response to inflammasome activation, catalyzes processing and inactivation of PARP1, alleviating the transcription repressor activity of PARP1. Acts as an inhibitor of type I interferon production during virus-induced apoptosis by mediating cleavage of antiviral proteins CGAS, IRF3 and MAVS, thereby preventing cytokine overproduction. Cleaves and activates sterol regulatory element binding proteins (SREBPs). Cleaves phospholipid scramblase proteins XKR4, XKR8 and XKR9. In case of infection, catalyzes cleavage of Kaposi sarcoma-associated herpesvirus protein ORF57, thereby preventing expression of viral lytic genes. Cleaves BIRC6 following inhibition of BIRC6-caspase binding by DIABLO/SMAC. Lacks enzymatic activity.

Subunit / interactions. Heterotetramer that consists of two anti-parallel arranged heterodimers, each one formed by a 20 kDa (p20) and a 11 kDa (p11) subunit. Interacts with XIAP (via its second BIR domain); inhibiting CASP7 activity. Interacts with BIRC6/bruce. Interacts with ATXN3 (short isoform 1). Interacts with HSPA5.

Subcellular location. Cytoplasm. Cytosol. Nucleus. Secreted. Extracellular space.

Tissue specificity. Highly expressed in lung, skeletal muscle, liver, kidney, spleen and heart, and moderately in testis. No expression in the brain.

Post-translational modifications. Cleavage by different proteases, such as granzyme B (GZMB), caspase-1 (CASP1), caspase-8 (CASP8), caspase-9 (CASP9) or caspase-10 (CASP10) generate the two active subunits. Its involvement in different programmed cell death processes is probably specified by the protease that activates CASP7. Cleaved and activated by initiator caspases (CASP8, CASP9 and/or CASP10), leading to execution phase of apoptosis. Cleavage and maturation by GZMB regulates granzyme-mediated programmed cell death. Cleaved and activated by CASP1 in response to bacterial infection. Propeptide domains can also be cleaved efficiently by CASP3. Active heterodimers between the small subunit of caspase-7 and the large subunit of CASP3, and vice versa, also occur. Also cleaved at the N-terminus at alternative sites by CAPN1, leading to its activation. Phosphorylation at Ser-30 and Ser-239 by PAK2 inhibits its activity. Phosphorylation at Ser-30 prevents cleavage and activation by initiator caspase CASP9, while phosphorylation at Ser-239 prevents thiol protease activity by preventing substrate-binding. (Microbial infection) ADP-riboxanation by C.violaceum CopC blocks CASP7 processing, preventing CASP7 activation and ability to recognize and cleave substrates. Ubiquitinated by BIRC6; this activity is inhibited by DIABLO/SMAC.

Activity regulation. During activation, the N-terminal disordered prodomain is removed by cleavage. Concomitantly, double cleavage gives rise to a large Caspase-7 subunit p20 and a small Caspase-7 subunit p11. The two large and two small subunits then assemble to form the active CASP7 complex. Can be cleaved and activated by different caspases, depending on the context. Cleaved and activated by initiator caspases (CASP8, CASP9 and/or CASP10), leading to execution phase of apoptosis. Inhibited by XIAP, which directly binds to the active site pocket and obstructs substrate entry. Cleavage and maturation by GZMB regulates granzyme-mediated programmed cell death. Cleavage and maturation by CASP1 regulates pyroptosis. Phosphorylation at Ser-30 and Ser-239 by PAK2 inhibits its activity. Inhibited by isatin sulfonamides. Inhibited by 2-(2,4-Dichlorophenoxy)- N-(2-mercapto-ethyl)-acetamide (DICA) and 5-Fluoro-1H-indole-2- carboxylic acid (2-mercapto-ethyl)-amide (FICA) allosteric inhibitors, which disrupt an interaction between Arg-187 and Tyr-223. Specifically inhibited by DARPin D7.18 and D7.43, which specifically bind to the precursor CASP7 and prevent its processing and activation. Inhibited by BIRC6; following inhibition of BIRC6-caspase binding by DIABLO/SMAC, BIRC6 is subjected to caspase cleavage, leading to an increase in active caspases.

Domain organisation. The exosite polybasic region mediates non-specific RNA-binding, acting as a bridge for RNA-binding target proteins, such as PARP1. The exosite is also required for interaction with non-RNA-binding proteins, such as Hsp90 co-chaperone PTGES3.

Similarity. Belongs to the peptidase C14A family.

Isoforms (4)

UniProt ID	Names	Canonical?
P55210-1	Alpha	yes
P55210-2	Beta
P55210-3	Alpha’, Beta
P55210-4	4

RefSeq proteins (8): NP_001218, NP_001253985, NP_001253986, NP_001253987, NP_001307840, NP_203124, NP_203125, NP_203126 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001309	Pept_C14_p20	Domain
IPR002138	Pept_C14_p10	Domain
IPR002398	Pept_C14	Family
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: PF00656

Enzyme classification (BRENDA):

• EC 3.4.22.60 — caspase-7 (BRENDA: 8 organisms, 155 substrates, 75 inhibitors, 35 Km, 27 kcat entries)

Substrate kinetics (BRENDA)

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

Substrate	Km (mM)	Measurements
N-ACETYL-DEVD-7-AMIDO-4-FLUOROMETHYLCOUMARIN	0.0298–0.0687	7
N-ACETYL-ASP-GLU-VAL-ASP-P-NITROANILIDE	0.0848–0.9365	5
AC-DEVD-7-AMIDO-4-METHYLCOUMARIN	0.041	2
AC-VEID-7-AMIDO-4-METHYLCOUMARIN	0.0054–0.2	2
ACETYL-DEVD-4-NITROANILIDE	0.012–0.0646	2
ACETYL-DEVD-7-AMIDO-4-METHYLCOUMARIN	0.015–0.1	2
AC-DVAD-P-NITROANILIDE	0.2193	1
AC-LDVAD-P-NITROANILIDE	0.3239	1
AC-VDVAD-P-NITROANILIDE	0.3149	1
ACETYL-DEVD-7-AMIDO-4-FLUOROMETHYLCOUMARIN	0.0605	1
ACETYL-DQMD-4-NITROANILIDE	0.13	1
ACETYL-VDQQD-4-NITROANILIDE	3.1	1
ACETYL-VDQVDGW-AMIDE	0.125	1
ACETYL-VDVAD-4-NITROANILIDE	0.2	1
ACETYL-VQVDGW-AMIDE	0.13	1

UniProt features (92 total): mutagenesis site 31, strand 13, helix 11, region of interest 6, modified residue 6, turn 6, site 5, splice variant 3, propeptide 2, active site 2, chain 2, sequence variant 2, initiator methionine 1, compositionally biased region 1, sequence conflict 1

Structure

Experimental structures (PDB)

47 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
4JR2	X-RAY DIFFRACTION	1.65
4JB8	X-RAY DIFFRACTION	1.7
2QL9	X-RAY DIFFRACTION	2.14
4JR1	X-RAY DIFFRACTION	2.15
5K20	X-RAY DIFFRACTION	2.2
2QLB	X-RAY DIFFRACTION	2.25
4LSZ	X-RAY DIFFRACTION	2.26
4ZVR	X-RAY DIFFRACTION	2.3
2QL5	X-RAY DIFFRACTION	2.34
1F1J	X-RAY DIFFRACTION	2.35
6CL2	X-RAY DIFFRACTION	2.35
1I4O	X-RAY DIFFRACTION	2.4
2QL7	X-RAY DIFFRACTION	2.4
1I51	X-RAY DIFFRACTION	2.45
3EDR	X-RAY DIFFRACTION	2.45
6X8L	X-RAY DIFFRACTION	2.45
3IBF	X-RAY DIFFRACTION	2.5
4ZVP	X-RAY DIFFRACTION	2.5
4ZVQ	X-RAY DIFFRACTION	2.5
4ZVS	X-RAY DIFFRACTION	2.5
1K86	X-RAY DIFFRACTION	2.6
2QLJ	X-RAY DIFFRACTION	2.6
5V6Z	X-RAY DIFFRACTION	2.6
4ZVU	X-RAY DIFFRACTION	2.6
6X8J	X-RAY DIFFRACTION	2.6
3H1P	X-RAY DIFFRACTION	2.61
6CL1	X-RAY DIFFRACTION	2.65
1K88	X-RAY DIFFRACTION	2.7
5IC6	X-RAY DIFFRACTION	2.7
3IBC	X-RAY DIFFRACTION	2.75

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P55210-F1	82.05	0.67

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 (7): 144; 186; 36–37 (cleavage; by capn1); 45–46 (cleavage; by capn1); 47–48 (cleavage; by capn1); 187 (involved in allosteric regulation); 223 (involved in allosteric regulation)

Post-translational modifications (6): 2, 30, 37, 173, 233, 239

Mutagenesis-validated functional residues (31):

Position	Phenotype
23	abolished cleavage at the n-terminus, leading to impaired activation and thiol protease activity. in p7-d2a mutant; abol
30	abolished phosphorylation by pak2; when associated with a-173 and a-239.
30	mimics phosphorylation; does not affect thiol protease activity.
38–41	decreased ability to cleave parp1 and ptges3.
38–41	decreased ability to cleave parp1.
39–40	does not affect ability to cleave parp1.
39–40	decreased ability to cleave parp1. decreased rna-binding.
39	decreased ability to cleave parp1.
173	abolished phosphorylation by pak2; when associated with a-30 and a-239.
186	abolished thiol protease activity.
187	does not significantly affect thiol protease catalytic efficiency.
187	reduced thiol protease catalytic efficiency.
187	strongly reduced thiol protease catalytic efficiency.
192	strongly reduced thiol protease activity.
195–206	in mutant ii; prevents cleavage of loop l2 region; retains significant thiol protease activity.
195–200	in mutant iii; prevents cleavage of loop l2 region; abolished thiol protease activity.
198–204	in mutant iv; prevents cleavage of loop l2 region; retains significant thiol protease activity.
198	strongly reduced cleavage and activation by initiator caspases. abolished cleavage and activation by initiator caspases;
206	reduced cleavage and activation by initiator caspases. abolished cleavage and activation by initiator caspases; when ass
223	does not significantly affect thiol protease catalytic efficiency.
229	strongly reduced thiol protease catalytic efficiency.
230–234	in escasp-7 v3 mutant; promotes specificity toward alternate peptides with veid, yvad, wehd, letd or lehd sequence; when
232–234	in dscasp-7 mutant; unable to cleave devd and veid peptides; when associated with f-276.
233	abolished adp-riboxanation by c.violaceum copc.
239	abolished phosphorylation by pak2; when associated with a-30 and a-173.

Function

Pathways and Gene Ontology

Reactome pathways

12 pathways

ID	Pathway
R-HSA-111459	Activation of caspases through apoptosome-mediated cleavage
R-HSA-111463	SMAC (DIABLO) binds to IAPs
R-HSA-111464	SMAC(DIABLO)-mediated dissociation of IAP:caspase complexes
R-HSA-111465	Apoptotic cleavage of cellular proteins
R-HSA-111469	SMAC, XIAP-regulated apoptotic response
R-HSA-264870	Caspase-mediated cleavage of cytoskeletal proteins
R-HSA-109581	Apoptosis
R-HSA-109606	Intrinsic Pathway for Apoptosis
R-HSA-111461	Cytochrome c-mediated apoptotic response
R-HSA-111471	Apoptotic factor-mediated response
R-HSA-5357801	Programmed Cell Death
R-HSA-75153	Apoptotic execution phase

MSigDB gene sets: 406 (showing top): GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_INFLAMMATORY_RESPONSE, GOBP_CELLULAR_RESPONSE_TO_LIPID, GOBP_CELLULAR_RESPONSE_TO_BIOTIC_STIMULUS, GRAESSMANN_APOPTOSIS_BY_SERUM_DEPRIVATION_UP, GRAESSMANN_RESPONSE_TO_MC_AND_SERUM_DEPRIVATION_UP, GOBP_PLASMA_MEMBRANE_ORGANIZATION, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, GOBP_STRIATED_MUSCLE_CELL_DIFFERENTIATION, GOBP_EXTRINSIC_APOPTOTIC_SIGNALING_PATHWAY, RAMJAUN_APOPTOSIS_BY_TGFB1_VIA_SMAD4_DN, GOBP_CELLULAR_RESPONSE_TO_OXYGEN_CONTAINING_COMPOUND, BAKER_HEMATOPOESIS_STAT1_TARGETS, BOYLAN_MULTIPLE_MYELOMA_D_DN, HERNANDEZ_MITOTIC_ARREST_BY_DOCETAXEL_1_DN

GO Biological Process (25): plasma membrane repair (GO:0001778), proteolysis (GO:0006508), apoptotic process (GO:0006915), heart development (GO:0007507), response to UV (GO:0009411), protein processing (GO:0016485), protein catabolic process (GO:0030163), defense response to bacterium (GO:0042742), positive regulation of neuron apoptotic process (GO:0043525), fibroblast apoptotic process (GO:0044346), ceramide biosynthetic process (GO:0046513), striated muscle cell differentiation (GO:0051146), neuron apoptotic process (GO:0051402), protein maturation (GO:0051604), lymphocyte apoptotic process (GO:0070227), cellular response to lipopolysaccharide (GO:0071222), cellular response to staurosporine (GO:0072734), execution phase of apoptosis (GO:0097194), positive regulation of plasma membrane repair (GO:1905686), negative regulation of transcription by RNA polymerase II (GO:0000122), regulation of transcription by RNA polymerase II (GO:0006357), positive regulation of canonical NF-kappaB signal transduction (GO:0043123), protein poly-ADP-ribosylation (GO:0070212), pyroptotic inflammatory response (GO:0070269), leukocyte apoptotic process (GO:0071887)

GO Molecular Function (8): RNA binding (GO:0003723), aspartic-type endopeptidase activity (GO:0004190), cysteine-type endopeptidase activity (GO:0004197), peptidase activity (GO:0008233), cysteine-type peptidase activity (GO:0008234), catalytic activity (GO:0003824), protein binding (GO:0005515), hydrolase activity (GO:0016787)

GO Cellular Component (8): fibrillar center (GO:0001650), obsolete extracellular space (GO:0005615), nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), cytosol (GO:0005829), plasma membrane (GO:0005886), extracellular region (GO:0005576)

Reactome top-level categories

Rollup of top-8 pathways:

Category	Pathways
SMAC, XIAP-regulated apoptotic response	2
Apoptotic factor-mediated response	2
Apoptosis	2
Cytochrome c-mediated apoptotic response	1
Apoptotic execution phase	1
Apoptotic cleavage of cellular proteins	1
Programmed Cell Death	1
Intrinsic Pathway for Apoptosis	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	5
protein metabolic process	3
apoptotic process	3
endopeptidase activity	2
plasma membrane organization	1
wound healing	1
programmed cell death	1
apoptotic signaling pathway	1
execution phase of apoptosis	1
animal organ development	1
circulatory system development	1
response to light stimulus	1
proteolysis	1
protein maturation	1
macromolecule catabolic process	1
defense response	1
response to bacterium	1
positive regulation of apoptotic process	1
regulation of neuron apoptotic process	1
neuron apoptotic process	1
ceramide metabolic process	1
sphingolipid biosynthetic process	1
muscle cell differentiation	1
gene expression	1
leukocyte apoptotic process	1
response to lipopolysaccharide	1
cellular response to molecule of bacterial origin	1
cellular response to lipid	1
cellular response to oxygen-containing compound	1
cellular response to alkaloid	1
response to staurosporine	1
cellular process	1
bleb assembly	1
plasma membrane repair	1
positive regulation of cellular component organization	1
regulation of plasma membrane repair	1
regulation of transcription by RNA polymerase II	1
transcription by RNA polymerase II	1
negative regulation of DNA-templated transcription	1
nucleic acid binding	1

Protein interactions and networks

STRING

2378 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CASP7	XIAP	P98170	997
CASP7	HSPA5	P11021	933
CASP7	CYCS	P00001	904
CASP7	APAF1	O14727	879
CASP7	BIRC7	Q96CA5	872
CASP7	PARP1	P09874	849
CASP7	BCL2	P10415	836
CASP7	BCL2L1	Q07817	822
CASP7	BIRC2	Q13490	809
CASP7	BCL2L12	Q9HB09	799
CASP7	CASP8	Q14790	789
CASP7	DIABLO	Q9NR28	779
CASP7	ANXA5	P08758	731
CASP7	GAPDH	P00354	730
CASP7	TNFRSF10B	O14763	711

IntAct

80 interactions, top by confidence:

A	B	Type	Score
CASP7	XIAP	psi-mi:“MI:0407”(direct interaction)	0.840
XIAP	CASP7	psi-mi:“MI:0915”(physical association)	0.840
CASP7	XIAP	psi-mi:“MI:0914”(association)	0.840
SAT1	CASP7	psi-mi:“MI:0915”(physical association)	0.720
CASP7	SAT1	psi-mi:“MI:0915”(physical association)	0.720
CASP7	BIRC2	psi-mi:“MI:0915”(physical association)	0.640
HTRA4	CASP7	psi-mi:“MI:0403”(colocalization)	0.620
HTRA4	CASP7	psi-mi:“MI:2364”(proximity)	0.620
CASP7	HTRA4	psi-mi:“MI:0194”(cleavage reaction)	0.620
CASP7	PAK2	psi-mi:“MI:0915”(physical association)	0.620
PAK2	CASP7	psi-mi:“MI:0915”(physical association)	0.620
PAK2	CASP7	psi-mi:“MI:0403”(colocalization)	0.620
PAK2	CASP7	psi-mi:“MI:0217”(phosphorylation reaction)	0.620
CASP7	PAK2	psi-mi:“MI:0217”(phosphorylation reaction)	0.620
CASP7	NIF3L1	psi-mi:“MI:0915”(physical association)	0.560
MAGEA11	CASP7	psi-mi:“MI:0915”(physical association)	0.560
PIK3R1	CASP7	psi-mi:“MI:0915”(physical association)	0.560
SKAP1	CASP7	psi-mi:“MI:0915”(physical association)	0.560
CASP7	KLHL36	psi-mi:“MI:0915”(physical association)	0.560
HTT	CASP7	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (120): PTGES3 (Biochemical Activity), PARP1 (Biochemical Activity), CASP7 (Co-fractionation), SAT1 (Two-hybrid), CASP7 (Affinity Capture-MS), CASP7 (Reconstituted Complex), MAPT (Biochemical Activity), CASP7 (Affinity Capture-MS), CASP7 (Affinity Capture-Western), CTBP1 (Affinity Capture-MS), CASP7 (Affinity Capture-MS), CASP7 (Affinity Capture-Western), HSPA5 (Affinity Capture-Western), CASP7 (Two-hybrid), MAGEA11 (Two-hybrid)

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: A0A1D5PPP7, F1NV61, O01382, O02002, O08738, O35397, O89110, P29452, P42573, P42574, P55210, P55211, P55212, P55213, P55214, P55866, P70677, P89116, P97864, Q08DY9, Q14790, Q2PFV2, Q3T0P5, Q5IS54, Q5IS99, Q60431, Q8C3Q9, Q8MJC3, Q8MJU1, Q8MKI5, Q92851, Q95ND5, Q9JHX4, G5EBM1, G5ECW5, O15519, O89094, P31944, P42575, P45436

SIGNOR signaling

15 interactions.

A	Effect	B	Mechanism
CASP8	up-regulates	CASP7	cleavage
PAK2	down-regulates	CASP7	phosphorylation
“Caspase 8 complex”	up-regulates	CASP7	cleavage
SRC	“up-regulates activity”	CASP7	phosphorylation
CASP7	down-regulates	PARP1	cleavage
XIAP	“down-regulates quantity by destabilization”	CASP7	binding
CASP7	“form complex”	“Caspase 7 complex”	binding
CASP7	“up-regulates activity”	PSEN2	cleavage
CASP7	“up-regulates activity”	PSEN1	cleavage

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 34 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.

GO biological processes:

GO term	Partners	Fold	FDR
positive regulation of apoptotic process	6	10.3×	2e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	46
Likely benign	9
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

1193 predictions. Top by Δscore:

Variant	Effect	Δscore
10:113697488:TCCCA:T	acceptor_gain	1.0000
10:113697489:CCCA:C	acceptor_gain	1.0000
10:113697489:CCCAG:C	acceptor_loss	1.0000
10:113697490:CCA:C	acceptor_gain	1.0000
10:113697490:CCAG:C	acceptor_loss	1.0000
10:113697491:CAG:C	acceptor_gain	1.0000
10:113697492:A:AG	acceptor_gain	1.0000
10:113697492:A:C	acceptor_gain	1.0000
10:113697492:AGAT:A	acceptor_gain	1.0000
10:113697492:AGATG:A	acceptor_gain	1.0000
10:113697493:G:A	acceptor_gain	1.0000
10:113697493:G:GA	acceptor_gain	1.0000
10:113697493:GA:G	acceptor_gain	1.0000
10:113697493:GAT:G	acceptor_gain	1.0000
10:113697493:GATG:G	acceptor_gain	1.0000
10:113697493:GATGG:G	acceptor_gain	1.0000
10:113697599:TTCAG:T	donor_gain	1.0000
10:113697600:TCAG:T	donor_gain	1.0000
10:113697601:CAG:C	donor_gain	1.0000
10:113697602:AG:A	donor_gain	1.0000
10:113697603:GG:G	donor_gain	1.0000
10:113697604:G:GA	donor_loss	1.0000
10:113697604:G:GG	donor_gain	1.0000
10:113697605:T:G	donor_loss	1.0000
10:113721648:CAGG:C	acceptor_loss	1.0000
10:113721649:AG:A	acceptor_gain	1.0000
10:113721650:GG:G	acceptor_gain	1.0000
10:113721650:GGT:G	acceptor_gain	1.0000
10:113721650:GGTA:G	acceptor_gain	1.0000
10:113721650:GGTAT:G	acceptor_gain	1.0000

AlphaMissense

2027 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
10:113721153:T:C	F78L	0.999
10:113721155:T:A	F78L	0.999
10:113721155:T:G	F78L	0.999
10:113725412:A:C	S143R	0.999
10:113725414:C:A	S143R	0.999
10:113725414:C:G	S143R	0.999
10:113725518:C:A	P178H	0.999
10:113725522:A:C	K179N	0.999
10:113725522:A:T	K179N	0.999
10:113726411:T:C	L220P	0.999
10:113721136:T:A	I72K	0.998
10:113721680:G:C	D93H	0.998
10:113725400:T:C	C139R	0.998
10:113725417:T:A	H144Q	0.998
10:113725417:T:G	H144Q	0.998
10:113725482:T:C	F166S	0.998
10:113725517:C:T	P178S	0.998
10:113725524:T:C	L180P	0.998
10:113725527:T:C	F181S	0.998
10:113726405:A:T	D218V	0.998
10:113726423:C:T	S224F	0.998
10:113729489:G:C	Q287H	0.998
10:113729489:G:T	Q287H	0.998
10:113729512:T:C	L295P	0.998
10:113721129:T:C	C70R	0.997
10:113721131:C:G	C70W	0.997
10:113721136:T:G	I72R	0.997
10:113721139:T:A	I73K	0.997
10:113721663:G:C	R87P	0.997
10:113725415:C:G	H144D	0.997

dbSNP variants (sampled 300 via entrez): RS1000004690 (10:113723828 C>T), RS1000096353 (10:113708593 T>A,C), RS1000106779 (10:113717683 C>T), RS1000139701 (10:113717965 A>G), RS1000157495 (10:113691931 T>A,C), RS1000207704 (10:113686888 A>G), RS1000237526 (10:113698570 T>C), RS1000312879 (10:113691662 A>G), RS1000338404 (10:113728510 G>T), RS1000359232 (10:113698095 A>G), RS1000374670 (10:113705726 G>C), RS1000451437 (10:113711252 G>A), RS1000470975 (10:113679214 C>T), RS1000518140 (10:113692472 C>G), RS1000574806 (10:113697183 G>C)

Disease associations

OMIM: gene MIM:601761 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST001509_8	Vitiligo	4.000000e-08
GCST004785_44	Vitiligo	4.000000e-12
GCST007327_55	Smoking status (ever vs never smokers)	1.000000e-08
GCST012013_24	Cataracts	5.000000e-15

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004318	smoking behavior

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (3): CHEMBL3430905 (PROTEIN FAMILY), CHEMBL3468 (SINGLE PROTEIN), CHEMBL3831289 (PROTEIN FAMILY)

Molecules with ChEMBL bioactivity

32 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 1,471,976 (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
CHEMBL1201038	ACRISORCIN	4	1,956
CHEMBL1351	CARBOPLATIN	4
CHEMBL1447476	BITHIONOLATE SODIUM	4	324
CHEMBL1534	RIBOFLAVIN	4	136,163
CHEMBL1554	DACTINOMYCIN	4	175,245
CHEMBL1607	TOPOTECAN HYDROCHLORIDE	4	56,379
CHEMBL255044	FLUPIRTINE	4	5,706
CHEMBL290106	BITHIONOL	4	6,439
CHEMBL34259	METHOTREXATE	4	398,396
CHEMBL43	AMSACRINE	4	82,326
CHEMBL43128	PRIMAQUINE PHOSPHATE	4	2,032
CHEMBL496	HEXACHLOROPHENE	4	26,164
CHEMBL572	NITROFURANTOIN	4	26,231
CHEMBL585	TRIAMTERENE	4	21,663
CHEMBL704	MESALAMINE	4	52,574
CHEMBL772	RESERPINE	4	330,645
CHEMBL932	DIPYRIDAMOLE	4	51,743
CHEMBL119443	ERGONOVINE	3	3,432
CHEMBL1255653	SEPIAPTERIN	3	676
CHEMBL140	CURCUMIN	3	93,882
CHEMBL273862	HYDROXYCAMPTOTHECIN	3
CHEMBL41286	DIACEREIN	3
CHEMBL51483	GOSSYPOL	3
CHEMBL12208	HYMECROMONE	2
CHEMBL284328	HOMIDIUM BROMIDE	2
CHEMBL31574	FISETIN	2
CHEMBL351585	PAPAVEROLINE	2
CHEMBL376180	AMINOPTERIN	2
CHEMBL43184	AMINACRINE	2
CHEMBL295316	PLUMBAGIN	1

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

PharmGKB clinical annotations

6 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs1127687	Efficacy	3	gemcitabine;Platinum compounds	Non-Small Cell Lung Carcinoma
rs1127687	Efficacy	3	paclitaxel;Platinum compounds	Non-Small Cell Lung Carcinoma
rs12415607	Efficacy	3	docetaxel;gemcitabine;paclitaxel;Platinum compounds;vinorelbine	Non-Small Cell Lung Carcinoma
rs2227310	Efficacy	3	docetaxel;gemcitabine;paclitaxel;Platinum compounds;vinorelbine	Non-Small Cell Lung Carcinoma
rs4353229	Efficacy	3	docetaxel;gemcitabine;paclitaxel;Platinum compounds;vinorelbine	Non-Small Cell Lung Carcinoma
rs7921977	Efficacy	3	docetaxel;gemcitabine;paclitaxel;Platinum compounds;vinorelbine	Non-Small Cell Lung Carcinoma

PharmGKB variants

5 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs1127687	CASP7	3	2.00	2	paclitaxel;Platinum compounds;gemcitabine;Platinum compounds
rs2227310	CASP7	3	5.50	1	docetaxel;gemcitabine;paclitaxel;Platinum compounds;vinorelbine
rs4353229	CASP7	3	3.50	1	docetaxel;gemcitabine;paclitaxel;Platinum compounds;vinorelbine
rs7921977	CASP7	3	0.50	1	docetaxel;gemcitabine;paclitaxel;Platinum compounds;vinorelbine
rs12415607	CASP7	3	3.50	1	docetaxel;gemcitabine;paclitaxel;Platinum compounds;vinorelbine

GtoPdb / IUPHAR curated pharmacology

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

Target class: enzyme — C14: Caspase

Most potent curated ligand interactions (3 total), top 3:

Ligand	Action	Affinity	Parameter
isatin sulfonamide 34 [PMID: 11384246]	Inhibition	8.2	pKi
M826	Inhibition	7.89	pIC50
compound 4 [PMID: 12408711]	Inhibition	6.89	pKi

Binding affinities (BindingDB)

94 measured of 192 human assays (196 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
5-{[(4-{[(2S)-1-carboxy-3-oxopropan-2-yl]carbamoyl}phenyl)methyl]sulfamoyl}-2-hydroxybenzoic acid	KI	160 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
CID6851947	EC50	220 nM	US-10166229: Compounds and methods for the treatment of cancer
4-oxo-4-(piperidin-1-yl)-N-(1,3,4-trioxo-1,2,3,4-tetrahydroisoquinolin-6-yl)butanamide	IC50	231 nM
2-oxo-1-phenyl-2-[(1,3,4-trioxo-1,2,3,4-tetrahydroisoquinolin-5-yl)amino]ethyl acetate	IC50	233 nM
Z-Asp-(D,L Ala(2’-quinolyl))-Val- Aspphenyl vinylsulfone	IC50	300 nM	US-10167313: Selective caspase inhibitors and uses thereof
(5E)-2-(4-methoxyphenyl)-5-[(3,4,5-trimethoxyphenyl)methylidene]-4-oxazolone	EC50	420 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
3-Chloro-N-(1,2,3,4-tetrahydro-1,3,4-trioxoisoquinolin-6-yl)-propanamide	IC50	530 nM
N-(2-Methoxy-phenyl)-N-(1,3,4-trioxo-1,2,3,4-tetrahydro-isoquinolin-6-yl)-succinamide	IC50	537 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
N-(1,3,4-Trioxo-1,2,3,4-tetrahydro-isoquinolin-6-yl)-succinamic acid	IC50	859 nM
(3S)-5-(benzylsulfanyl)-3-[(2S)-2-[(3,5-dibromophenyl)formamido]-3-methylbutanamido]-4-oxopentanoic acid	IC50	860 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)-5-(benzylsulfanyl)-3-[(2S)-2-[(2R)-2-(5-bromo-2-methoxyphenyl)pent-4-ynamido]-3-methylbutanamido]-4-oxopentanoic acid	IC50	1030 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
4-[(2-oxidanylidenebenzo[cd]indol-1-yl)methyl]-N’-[(E)-(2-oxidanyl-4-oxidanylidene-cyclohexa-2,5-dien-1-ylidene)methyl]benzohydrazide	IC50	1470 nM
(S)-5-({5-[1-Carboxymethyl-3-(2-chloro-benzylsulfanyl)-2-oxo-propylcarbamoyl]pyridin-2-ylmethyl}sulfamoyl)-2-hydroxy-benzoic Acid	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)-3-[(2S)-2-[(2S)-2-[(3S)-3-formamido-3-(phenylformamido)propanoic acid]propanamido]-3-methylbutanamido]-4-oxo-7-phenylheptanoic acid	IC50	1650 nM
6-methyl-2-(1-naphthalenyl)-5-benzotriazolamine	EC50	1750 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
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
(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
(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
(3S)-5-(benzylsulfanyl)-3-[(2S)-2-[(2S)-2-hydroxy-3-methylbutanamido]-3-methylbutanamido]-4-oxopentanoic acid	IC50	3020 nM
valine aspartyl ketone 29	IC50	3040 nM
Thiophene Scaffold 66b	KI	3200 nM
N-(3-prop-2-enyl-6-sulfamoyl-1,3-benzothiazol-2-ylidene)-2-thiophen-2-ylquinoline-4-carboxamide	EC50	3260 nM
isatin Michael acceptor (IMA) analogue, 18a	IC50	3300 nM
2-(2-methoxyanilino)-8-methyl-3-quinolinecarbonitrile	EC50	3540 nM
(3S)-3-[(2S)-2-{1-[5-(carboxymethoxy)-2-ethoxyphenyl]acetamido}-3-methylbutanamido]-5-{[(2-chloro-6-fluorophenyl)methyl]sulfanyl}-4-oxopentanoic acid	IC50	3800 nM
isatin Michael acceptor (IMA) analogue, 12a	IC50	3880 nM
Pyridine Scaffold 4	KI	3900 nM
(3S)-5-(benzylsulfanyl)-3-[(2S)-2-[(2S)-2-hydroxy-2-phenylacetamido]-3-methylbutanamido]-4-oxopentanoic acid	IC50	4060 nM
isatin Michael acceptor (IMA) analogue, 11a	IC50	4100 nM
(3S)-5-(benzylsulfanyl)-3-[(2S)-2-[(2R)-2-hydroxy-2-phenylacetamido]-3-methylbutanamido]-4-oxopentanoic acid	IC50	4160 nM
isatin Michael acceptor (IMA) analogue, 18b	IC50	4180 nM
(3S)-5-{[(2-chloro-6-fluorophenyl)methyl]sulfanyl}-3-[(2S)-2-(1-{2-ethoxy-5-[2-oxo-2-(propan-2-yloxy)ethoxy]phenyl}acetamido)-3-methylbutanamido]-4-oxopentanoic acid	IC50	4200 nM
2-(2,3-dihydro-1,4-benzodioxin-2-yl)-4-[3-(trifluoromethyl)phenyl]-1,3-thiazole	KI	4300 nM
isatin Michael acceptor (IMA) analogue, 13b	IC50	4300 nM
(3S)-5-(benzylsulfanyl)-3-[(2S)-2-[2-(2,5-dimethoxyphenyl)-2-hydroxyacetamido]-3-methylbutanamido]-4-oxopentanoic acid	IC50	4490 nM

ChEMBL bioactivities

1282 potent at pChembl≥5 of 2951 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
9.22	IC50	0.6	nM	CHEMBL467252
9.02	IC50	0.951	nM	CHEMBL2381343
8.80	Ki	1.6	nM	CHEMBL5723373
8.74	IC50	1.8	nM	CHEMBL217457
8.72	IC50	1.9	nM	CHEMBL523666
8.70	EC50	2	nM	CHEMBL5289751
8.66	EC50	2.2	nM	CHEMBL456799
8.64	EC50	2.3	nM	CHEMBL515506
8.62	IC50	2.4	nM	CHEMBL494220
8.54	IC50	2.9	nM	CHEMBL417149
8.53	IC50	2.95	nM	CHEMBL417149
8.48	IC50	3.3	nM	CHEMBL3359194
8.42	IC50	3.8	nM	CHEMBL1762363
8.40	IC50	4	nM	CHEMBL217777
8.34	IC50	4.6	nM	CHEMBL215480
8.30	IC50	5	nM	CHEMBL466422
8.27	IC50	5.4	nM	CHEMBL3133258
8.23	IC50	5.9	nM	CHEMBL213759
8.22	IC50	5.95	nM	CHEMBL3359196
8.22	Ki	6	nM	CHEMBL439753
8.21	IC50	6.1	nM	CHEMBL217777
8.21	IC50	6.1	nM	CHEMBL1762362
8.18	IC50	6.6	nM	CHEMBL227036
8.17	IC50	6.8	nM	CHEMBL494141
8.15	IC50	7	nM	CHEMBL23226
8.14	IC50	7.2	nM	CHEMBL513663
8.13	IC50	7.47	nM	CHEMBL2348860
8.12	IC50	7.6	nM	CHEMBL492385
8.12	Ki	7.5	nM	CHEMBL5641709
8.10	IC50	8	nM	CHEMBL443565
8.10	IC50	8	nM	CHEMBL248508
8.10	EC50	8	nM	CHEMBL516490
8.09	IC50	8.1	nM	CHEMBL521840
8.08	IC50	8.4	nM	CHEMBL352426
8.05	IC50	9	nM	CHEMBL513297
8.03	IC50	9.424	nM	CHEMBL3233629
8.02	IC50	9.6	nM	CHEMBL3133259
8.01	IC50	9.68	nM	CHEMBL2348702
8.01	IC50	9.7	nM	CHEMBL3359202
8.00	IC50	10	nM	CHEMBL178116
8.00	IC50	10	nM	CHEMBL185356
8.00	IC50	10	nM	CHEMBL100588
8.00	IC50	10	nM	CHEMBL430648
8.00	IC50	10	nM	CHEMBL328412
7.99	IC50	10.2	nM	CHEMBL1762350
7.96	IC50	11	nM	CHEMBL180263
7.96	IC50	11	nM	CHEMBL237310
7.96	IC50	11	nM	CHEMBL522148
7.96	IC50	11	nM	CHEMBL521822
7.95	IC50	11.2	nM	CHEMBL3133148

PubChem BioAssay actives

601 with measured affinity, of 851 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
5-[(2S)-2-(methoxymethyl)pyrrolidin-1-yl]sulfonyl-1-[(4-prop-2-enoxyphenyl)methyl]indole-2,3-dione	375064: Inhibition of human recombinant caspase 7 assessed as accumulation of cleaved fluorogenic 7-amino-4-methylcoumarin after 10 mins	ic50	0.0006	uM
1-[(3S)-3-fluoro-4-hydroxybutyl]-5-[(2S)-2-(methoxymethyl)pyrrolidin-1-yl]sulfonylindole-2,3-dione	748007: Inhibition of human recombinant caspase-7 assessed as Ac-DEVD-AMC conversion to 7-amino-4-methylcoumarin incubated for 10 mins prior to substrate addition measured after 10 mins by spectrophotometric analysis	ic50	0.0010	uM
1-[(4-iodophenyl)methyl]-5-[(2S)-2-(methoxymethyl)pyrrolidin-1-yl]sulfonylindole-2,3-dione	271891: Inhibition of caspase 7	ic50	0.0018	uM
5-[(2S)-2-(methoxymethyl)pyrrolidin-1-yl]sulfonyl-1-[[4-(oxiran-2-yl)phenyl]methyl]indole-2,3-dione	375064: Inhibition of human recombinant caspase 7 assessed as accumulation of cleaved fluorogenic 7-amino-4-methylcoumarin after 10 mins	ic50	0.0019	uM
(2S,4R)-1-[(2S)-2-[[2-[3-[2-[2-[2-[[2-[(9S)-7-(4-chlorophenyl)-4,5,13-trimethyl-3-thia-1,8,11,12-tetrazatricyclo[8.3.0.02,6]trideca-2(6),4,7,10,12-pentaen-9-yl]acetyl]amino]ethoxy]ethoxy]ethoxy]-2-[2-[2-[2-[[2-[(9S)-7-(4-chlorophenyl)-4,5,13-trimethyl-3-thia-1,8,11,12-tetrazatricyclo[8.3.0.02,6]trideca-2(6),4,7,10,12-pentaen-9-yl]acetyl]amino]ethoxy]ethoxy]ethoxymethyl]-2-methylpropoxy]acetyl]amino]-3,3-dimethylbutanoyl]-4-hydroxy-N-[[4-(4-methyl-1,3-thiazol-5-yl)phenyl]methyl]pyrrolidine-2-carboxamide	1939901: Activation of caspase 3/7 in human 22Rv1 cells by Caspase-Glo reagent based analysis	ec50	0.0020	uM
5-[(2S)-2-[(2,4-difluorophenoxy)methyl]pyrrolidin-1-yl]sulfonyl-1-[[1-(2-fluoroethyl)triazol-4-yl]methyl]indole-2,3-dione	389837: Inhibition of human recombinant caspase 7 assessed as accumulation of 7-amino-4-methylcoumarin substrate	ec50	0.0022	uM
1-[(4-fluorophenyl)methyl]-5-[(2S)-2-(pyrimidin-4-yloxymethyl)pyrrolidin-1-yl]sulfonylindole-2,3-dione	389837: Inhibition of human recombinant caspase 7 assessed as accumulation of 7-amino-4-methylcoumarin substrate	ec50	0.0023	uM
5-[(2S)-2-(methoxymethyl)pyrrolidin-1-yl]sulfonyl-1-[[4-(oxiran-2-ylmethoxy)phenyl]methyl]indole-2,3-dione	375064: Inhibition of human recombinant caspase 7 assessed as accumulation of cleaved fluorogenic 7-amino-4-methylcoumarin after 10 mins	ic50	0.0024	uM
(4S)-4-[[(2S)-2-acetamido-3-carboxypropanoyl]amino]-5-[[(2S)-1-[[(2S)-1-carboxy-3-oxopropan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]amino]-5-oxopentanoic acid	1799017: Enzyme Inhibition Assay from Article 10.1021/jm900135r: “Synthesis and in vitro evaluation of sulfonamide isatin Michael acceptors as small molecule inhibitors of caspase-6.”	ic50	0.0029	uM
7-bromo-1-butyl-5-[(2S)-2-(methoxymethyl)pyrrolidin-1-yl]sulfonylindole-2,3-dione	1170194: Inhibition of human recombinant caspase 7 using Ac-DEVD-AMC substrate assessed as accumulation of cleaved fluorogenic product	ic50	0.0033	uM
1-[[1-(2-fluoroethyl)triazol-4-yl]methyl]-5-[(2S)-2-(pyridin-3-yloxymethyl)pyrrolidin-1-yl]sulfonylindole-2,3-dione	591190: Inhibition of caspase 7 by fluorometric assay	ic50	0.0038	uM
5-[(2S)-2-(methoxymethyl)pyrrolidin-1-yl]sulfonyl-1-[(4-methoxyphenyl)methyl]indole-2,3-dione	271891: Inhibition of caspase 7	ic50	0.0040	uM
1-[[4-(3-fluoro-2-hydroxypropoxy)phenyl]methyl]-5-[(2S)-2-(methoxymethyl)pyrrolidin-1-yl]sulfonylindole-2,3-dione	375064: Inhibition of human recombinant caspase 7 assessed as accumulation of cleaved fluorogenic 7-amino-4-methylcoumarin after 10 mins	ic50	0.0050	uM
7-bromo-1-(4-fluorobutyl)-5-[(2S)-2-(methoxymethyl)pyrrolidin-1-yl]sulfonylindole-2,3-dione	1170194: Inhibition of human recombinant caspase 7 using Ac-DEVD-AMC substrate assessed as accumulation of cleaved fluorogenic product	ic50	0.0060	uM
1-benzyl-5-[(2S)-2-(phenoxymethyl)pyrrolidin-1-yl]sulfonylindole-2,3-dione	1796419: Caspase Inhibition Assay from Article 10.1021/jm0100537: “Potent and selective nonpeptide inhibitors of caspases 3 and 7.”	ki	0.0060	uM
1-[[1-(2-fluoroethyl)triazol-4-yl]methyl]-5-[(2S)-2-(pyridin-3-yloxymethyl)azetidin-1-yl]sulfonylindole-2,3-dione	591190: Inhibition of caspase 7 by fluorometric assay	ic50	0.0061	uM
1-[(4-bromophenyl)methyl]-5-[(2S)-2-(pyridin-3-yloxymethyl)pyrrolidin-1-yl]sulfonylindole-2,3-dione	292078: Inhibition of human recombinant caspase 7	ic50	0.0066	uM
1-(3-fluorobutyl)-5-[(2S)-2-(methoxymethyl)pyrrolidin-1-yl]sulfonylindole-2,3-dione	414667: Inhibition of human recombinant caspase 7	ic50	0.0068	uM
5-fluoro-3-[[(2S)-3-methyl-2-(phenylmethoxycarbonylamino)butanoyl]amino]-4-oxopentanoic acid	49566: Compound was evaluated for its inhibitory activity against the Caspase-7 enzyme	ic50	0.0070	uM
1-[(4-ethenylphenyl)methyl]-5-[(2S)-2-(methoxymethyl)pyrrolidin-1-yl]sulfonylindole-2,3-dione	375064: Inhibition of human recombinant caspase 7 assessed as accumulation of cleaved fluorogenic 7-amino-4-methylcoumarin after 10 mins	ic50	0.0072	uM
1-butyl-5-[(2S)-2-(2,2,2-trifluoroethoxymethyl)pyrrolidin-1-yl]sulfonylindole-2,3-dione	740439: Inhibition of human recombinant caspase 7 assessed as decrease in AMC release using Ac-Asp-Glu-Val-Asp-AMC as substrate preincubated with enzyme for 10 mins prior to substrate addition measured after 10 mins by fluorescence microplate analysis	ic50	0.0075	uM
1-[[4-(1-fluoro-2-hydroxyethyl)phenyl]methyl]-5-[(2S)-2-(methoxymethyl)pyrrolidin-1-yl]sulfonylindole-2,3-dione	375064: Inhibition of human recombinant caspase 7 assessed as accumulation of cleaved fluorogenic 7-amino-4-methylcoumarin after 10 mins	ic50	0.0076	uM
(3S)-3-[2-[5-tert-butyl-2-oxo-3-(2H-tetrazol-5-ylamino)pyrazin-1-yl]butanoylamino]-4-oxo-7-phenylheptanoic acid	306145: Inhibition of human recombinant caspase 7	ic50	0.0080	uM
5-[(2S)-2-[(4-fluorophenoxy)methyl]pyrrolidin-1-yl]sulfonyl-1-[(4-fluorophenyl)methyl]indole-2,3-dione	389837: Inhibition of human recombinant caspase 7 assessed as accumulation of 7-amino-4-methylcoumarin substrate	ec50	0.0080	uM
(3S)-3-[[(2S)-2-[[(2S)-2-[[(2S)-2-acetamido-3-carboxypropanoyl]amino]-4-carboxybutanoyl]amino]-3-methylbutanoyl]amino]-4-oxo-7-phenylheptanoic acid	241558: Inhibitory concentration against recombinant human caspase-7 in neuronal precursor (NT2) cells	ic50	0.0080	uM
1-butyl-5-[(2S)-2-(methoxymethyl)pyrrolidin-1-yl]sulfonylindole-2,3-dione	1170194: Inhibition of human recombinant caspase 7 using Ac-DEVD-AMC substrate assessed as accumulation of cleaved fluorogenic product	ic50	0.0081	uM
(3S)-3-[[(2S)-2-[[(2S)-2-[[(2S)-2-benzamido-3-carboxypropanoyl]amino]propanoyl]amino]-3-methylbutanoyl]amino]-4-oxo-7-phenylheptanoic acid	1796494: Caspase Inhibition Assay from Article 10.1016/j.bmcl.2003.10.064: “Discovery of novel aspartyl ketone dipeptides as potent and selective caspase-3 inhibitors.”	ic50	0.0084	uM
5-[(2S)-2-(methoxymethyl)pyrrolidin-1-yl]sulfonyl-1-[[(2S)-oxiran-2-yl]methyl]indole-2,3-dione	375064: Inhibition of human recombinant caspase 7 assessed as accumulation of cleaved fluorogenic 7-amino-4-methylcoumarin after 10 mins	ic50	0.0090	uM
N-(3-morpholin-4-ylphenyl)-3-oxo-1,2-benzothiazole-2-carboxamide	1125750: Inhibition of human recombinant caspase-7 using Ac-DEVD-AMC as substrate after 10 mins by fluorescence assay	ic50	0.0094	uM
1-butyl-7-fluoro-5-[(2S)-2-(methoxymethyl)pyrrolidin-1-yl]sulfonylindole-2,3-dione	1170194: Inhibition of human recombinant caspase 7 using Ac-DEVD-AMC substrate assessed as accumulation of cleaved fluorogenic product	ic50	0.0097	uM
1-(4-fluorobutyl)-5-[(2S)-2-(2-fluoroethoxymethyl)pyrrolidin-1-yl]sulfonylindole-2,3-dione	740439: Inhibition of human recombinant caspase 7 assessed as decrease in AMC release using Ac-Asp-Glu-Val-Asp-AMC as substrate preincubated with enzyme for 10 mins prior to substrate addition measured after 10 mins by fluorescence microplate analysis	ic50	0.0097	uM
3-[[(2S)-2-[(2,4-dichlorophenyl)methoxycarbonylamino]-3-methylbutanoyl]amino]-5-fluoro-4-oxopentanoic acid	240703: Inhibition concentration required against caspase-7	ic50	0.0100	uM
(4S)-4-[[(2S)-2-acetamido-3-carboxypropanoyl]amino]-5-[[(2S)-1-[[(3S)-2-hydroxy-5-oxooxolan-3-yl]amino]-3-methyl-1-oxobutan-2-yl]amino]-5-oxopentanoic acid	49705: Inhibitory concentration of compound required against Caspase-7 enzyme compared to acylated dipeptides	ic50	0.0100	uM
(4S)-5-[[(2S)-1-[[(3S)-2-hydroxy-5-oxooxolan-3-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-5-oxo-4-(phenylmethoxycarbonylamino)pentanoic acid	49703: Inhibitory concentration of compound required against Caspase-7 compared to acylated dipeptides	ic50	0.0100	uM
(4S)-4-[[(2R)-2-acetamido-2-carboxyacetyl]amino]-5-[[(2S)-1-[[(3S)-2-hydroxy-5-oxooxolan-3-yl]amino]-3-methyl-1-oxobutan-2-yl]amino]-5-oxopentanoic acid	49703: Inhibitory concentration of compound required against Caspase-7 compared to acylated dipeptides	ic50	0.0100	uM
(3S)-3-[[(2S)-2-[3-[[(2S)-2-acetamido-3-carboxypropanoyl]amino]-2-oxo-1-pyridinyl]butanoyl]amino]-5-benzylsulfanyl-4-oxopentanoic acid	241558: Inhibitory concentration against recombinant human caspase-7 in neuronal precursor (NT2) cells	ic50	0.0100	uM
1-[(4-methoxyphenyl)methyl]-5-[(2S)-2-(pyridin-3-yloxymethyl)azetidin-1-yl]sulfonylindole-2,3-dione	591190: Inhibition of caspase 7 by fluorometric assay	ic50	0.0102	uM
5-fluoro-3-[[(2S)-3-methyl-2-(phenylcarbamoyloxy)butanoyl]amino]-4-oxopentanoic acid	240591: Inhibitory concentration against Caspase-7	ic50	0.0110	uM
4-fluoro-2-[[2-[[(2S)-3-methyl-2-(phenylmethoxycarbonylamino)butanoyl]amino]benzoyl]amino]-3-oxobutanoic acid	302016: Inhibition of human caspase 7	ic50	0.0110	uM
1-(4-hydroxybutyl)-5-[(2S)-2-(methoxymethyl)pyrrolidin-1-yl]sulfonylindole-2,3-dione	414667: Inhibition of human recombinant caspase 7	ic50	0.0110	uM
5-[(2S)-2-(methoxymethyl)pyrrolidin-1-yl]sulfonyl-1-[[4-(trifluoromethyl)phenyl]methyl]indole-2,3-dione	414667: Inhibition of human recombinant caspase 7	ic50	0.0110	uM
1-[[4-(2-fluoroethoxy)phenyl]methyl]-5-[(2S)-2-(pyridin-3-yloxymethyl)pyrrolidin-1-yl]sulfonylindole-2,3-dione	591190: Inhibition of caspase 7 by fluorometric assay	ic50	0.0113	uM
1-[(4-hydroxyphenyl)methyl]-5-[(2S)-2-(pyridin-3-yloxymethyl)pyrrolidin-1-yl]sulfonylindole-2,3-dione	292078: Inhibition of human recombinant caspase 7	ic50	0.0117	uM
1-[[4-[2-(2-fluoroethoxy)ethoxy]phenyl]methyl]-5-[(2S)-2-(phenoxymethyl)pyrrolidin-1-yl]sulfonylindole-2,3-dione	591190: Inhibition of caspase 7 by fluorometric assay	ic50	0.0119	uM
5-[(2S)-2-[(2,4-difluorophenoxy)methyl]pyrrolidin-1-yl]sulfonyl-1-[[4-(2-fluoroethoxy)phenyl]methyl]indole-2,3-dione	591190: Inhibition of caspase 7 by fluorometric assay	ic50	0.0123	uM
1-(4-fluorobutyl)-5-[(2S)-2-(2-methoxyethyl)pyrrolidin-1-yl]sulfonylindole-2,3-dione	740439: Inhibition of human recombinant caspase 7 assessed as decrease in AMC release using Ac-Asp-Glu-Val-Asp-AMC as substrate preincubated with enzyme for 10 mins prior to substrate addition measured after 10 mins by fluorescence microplate analysis	ic50	0.0123	uM
1-[[1-(2-fluoroethyl)triazol-4-yl]methyl]-5-[(2S)-2-(phenoxymethyl)pyrrolidin-1-yl]sulfonylindole-2,3-dione	591190: Inhibition of caspase 7 by fluorometric assay	ic50	0.0124	uM
5-[(2S)-2-[(2,4-difluorophenoxy)methyl]pyrrolidin-1-yl]sulfonyl-1-[(4-fluorophenyl)methyl]indole-2,3-dione	389837: Inhibition of human recombinant caspase 7 assessed as accumulation of 7-amino-4-methylcoumarin substrate	ec50	0.0130	uM
3-[2-[5-tert-butyl-3-[(4-methyl-1,2,5-oxadiazol-3-yl)methylamino]-2-oxopyrazin-1-yl]butanoylamino]-5-[hexyl(methyl)amino]-4-oxopentanoic acid;hydrochloride	241558: Inhibitory concentration against recombinant human caspase-7 in neuronal precursor (NT2) cells	ic50	0.0130	uM
5-[(2S)-2-(ethoxymethyl)pyrrolidin-1-yl]sulfonyl-1H-indole-2,3-dione	740439: Inhibition of human recombinant caspase 7 assessed as decrease in AMC release using Ac-Asp-Glu-Val-Asp-AMC as substrate preincubated with enzyme for 10 mins prior to substrate addition measured after 10 mins by fluorescence microplate analysis	ic50	0.0132	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Acetylcysteine	decreases expression, affects cleavage, decreases reaction, increases activity, affects cotreatment (+5 more)	18
Doxorubicin	increases expression, increases reaction, affects reaction, affects response to substance, affects cotreatment (+6 more)	15
Resveratrol	affects reaction, decreases reaction, increases cleavage, increases expression, increases activity (+2 more)	12
Arsenic Trioxide	increases reaction, decreases reaction, increases activity, affects cotreatment, increases cleavage (+1 more)	11
Bortezomib	affects cotreatment, increases activity, increases cleavage, affects cleavage, increases reaction (+1 more)	9
Quercetin	increases activity, decreases reaction, increases cleavage, increases expression	8
Paclitaxel	affects cotreatment, increases expression, increases reaction, decreases reaction, increases activity (+1 more)	8
Staurosporine	increases expression, increases cleavage, decreases reaction, increases activity	8
(+)-JQ1 compound	increases activity, increases response to substance, increases cleavage	7
Cisplatin	affects cotreatment, increases cleavage, increases expression, increases reaction, increases activity	7
Estradiol	increases expression, affects cotreatment, increases reaction, decreases activity, decreases expression (+2 more)	6
Etoposide	decreases reaction, increases activity, increases reaction, increases response to substance	6
Cadmium Chloride	decreases expression, increases abundance, increases cleavage, increases activity, decreases reaction	6
bisphenol A	decreases expression, increases cleavage, increases activity, increases expression	5
sodium arsenite	decreases expression, increases cleavage, increases expression, decreases reaction, increases activity	5
U 0126	increases activity, increases cleavage, increases reaction, decreases reaction	5
Dactinomycin	increases reaction, decreases expression, affects cotreatment, increases secretion, increases activity	5
Tretinoin	increases expression, affects cotreatment, increases activity, increases cleavage, increases reaction (+1 more)	5
Valproic Acid	affects expression, decreases reaction, increases cleavage, increases expression	5
Thapsigargin	decreases reaction, increases activity, increases cleavage	5
thymoquinone	decreases reaction, increases cleavage, increases expression	4
usnic acid	increases activity, increases reaction, decreases reaction, decreases expression	4
ON 01910	increases activity, increases cleavage	4
benzyloxycarbonyl-valyl-alanyl-aspartic acid	increases activity, affects cotreatment, increases cleavage, increases reaction, decreases reaction	4
Sorafenib	increases cleavage, affects cotreatment, increases activity	4
Capsaicin	affects cotreatment, increases cleavage, increases activity	4
Curcumin	decreases expression, increases cleavage, affects cotreatment, increases expression, increases reaction (+2 more)	4
Herbicides	affects cotreatment, increases activity, decreases reaction	4
Plant Extracts	decreases reaction, increases cleavage, increases activity	4
Rotenone	decreases expression, increases expression, decreases reaction, increases activity	4

ChEMBL screening assays

107 unique, capped per target: 99 binding, 8 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL3427881	Binding	Activation of Caspase 3/7 in human U937 cells assessed as cleavage of Ac-DEVD-AFC at 30 uM after 16 hrs by fluorescence assay relative to control	Removal of Metabolic Liabilities Enables Development of Derivatives of Procaspase-Activating Compound 1 (PAC-1) with Improved Pharmacokinetics. — J Med Chem
CHEMBL1613779	Functional	PUBCHEM_BIOASSAY: qHTS Assay for Allosteric/Competitive Inhibitors of Caspase-7. (Class of assay: confirmatory)	PubChem BioAssay data set

Cellosaurus cell lines

4 cell lines: 4 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B1M5	Abcam HeLa CASP7 KO	Cancer cell line	Female
CVCL_D6AI	HyCyte A-549 KO-hCASP7	Cancer cell line	Male
CVCL_SG96	HAP1 CASP7 (-) 1	Cancer cell line	Male
CVCL_SG97	HAP1 CASP7 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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