CASP3

Summary

CASP3 (caspase 3, HGNC:1504) is a protein-coding gene on chromosome 4q35.1, encoding Caspase-3 (P42574). Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis.

The protein encoded by this gene is a cysteine-aspartic acid protease that plays a central role in the execution-phase of cell apoptosis. The encoded protein cleaves and inactivates poly(ADP-ribose) polymerase while it cleaves and activates sterol regulatory element binding proteins as well as caspases 6, 7, and 9. This protein itself is processed by caspases 8, 9, and 10. It is the predominant caspase involved in the cleavage of amyloid-beta 4A precursor protein, which is associated with neuronal death in Alzheimer’s disease.

Source: NCBI Gene 836 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 28 total — 1 pathogenic
• GTEx eGene: eQTL in 23 tissues, sQTL in 39 (q < 0.05)
• ChEMBL bioactivity: 5 clinical-phase molecules tested; no curated mechanism-of-action drug
• Constraint (gnomAD): pLI 0.07 (LoF-tolerant), LOEUF 0.86 (unconstrained)
• MANE Select transcript: NM_004346
• Interaction hub: 7,530 STRING partners (top 1% of genes corpus-wide)

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:1504
Approved symbol	CASP3
Name	caspase 3
Location	4q35.1
Locus type	gene with protein product
Status	Approved
Aliases	CPP32, CPP32B, Yama, apopain
Ensembl gene	ENSG00000164305
Ensembl biotype	protein_coding
OMIM	600636
Entrez	836

Gene structure

Transcript identifiers

Ensembl transcripts: 36 — 30 protein_coding, 4 nonsense_mediated_decay, 2 retained_intron

MANE Select: ENST00000308394

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 3, TSL 3: 1, TSL 4: 1, TSL 5: 1

ENST00000308394, ENST00000393585, ENST00000393588, ENST00000447121, ENST00000517513, ENST00000523916, ENST00000700100, ENST00000700101, ENST00000700102, ENST00000700103, ENST00000700104, ENST00000872339, ENST00000872340, ENST00000872341, ENST00000872342, ENST00000872343, ENST00000872344, ENST00000872345, ENST00000872346, ENST00000872347, ENST00000939939, ENST00000939940, ENST00000939941, ENST00000939942, ENST00000939943, ENST00000939944, ENST00000939945, ENST00000939946, ENST00000972040, ENST00000972041, ENST00000972042, ENST00000972043, ENST00000984192, ENST00001082170, ENST00001082171, ENST00001139592

RefSeq mRNA: 10 — MANE Select: NM_004346 NM_001354777, NM_001354779, NM_001354780, NM_001354781, NM_001354782, NM_001354783, NM_001354784, NM_001440946, NM_004346, NM_032991

CCDS: CCDS3836, CCDS87283

Canonical transcript exons

ENST00000308394 — 8 exons

Exon	Start	End
ENSE00001083265	184635294	184635418
ENSE00001083266	184632268	184632396
ENSE00001083268	184631037	184631157
ENSE00001083271	184631765	184631940
ENSE00001215704	184648465	184648631
ENSE00001592717	184649395	184649447
ENSE00002443273	184638401	184638468
ENSE00003514002	184627696	184629501

Expression profiles

Bgee: expression breadth ubiquitous, 245 present calls, max score 95.17.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 43.2886 / max 1058.2623, expressed in 1808 samples.

Highest expression (Bgee): jejunal mucosa, rectum, epithelium of nasopharynx, nasopharynx, ventricular zone.

Genetic regulation across tissues (GTEx eQTL / sQTL)

CASP3 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 23 tissues and its splicing (sQTL) in 39 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

showing 20 of 62 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Cells Cultured fibroblasts	sqtl	6.6e-59	+1.28	4:184648576:C:T
Adipose Subcutaneous	sqtl	1.7e-38	+1.15	4:184648576:C:T
Testis	eqtl	2.2e-37	-0.56	4:184631944:T:G
Cells Cultured fibroblasts	eqtl	4.9e-35	-0.33	4:184648878:C:A
Cells EBV-transformed lymphocytes	sqtl	1.2e-34	+1.50	4:184648576:C:T
Artery Tibial	sqtl	1.5e-33	+1.03	4:184648576:C:T
Esophagus Muscularis	sqtl	3.1e-27	+1.02	4:184648576:C:T
Esophagus Mucosa	sqtl	1.4e-24	+1.04	4:184648576:C:T
Lung	sqtl	3.6e-24	+0.90	4:184648576:C:T
Adipose Visceral Omentum	sqtl	5.7e-23	+0.97	4:184648576:C:T
Muscle Skeletal	sqtl	4.7e-22	+0.82	4:184648576:C:T
Colon Transverse	sqtl	2.6e-21	+1.17	4:184648576:C:T
Artery Aorta	sqtl	8.3e-21	+0.93	4:184648576:C:T
Nerve Tibial	sqtl	8.8e-20	+0.81	4:184648576:C:T
Thyroid	sqtl	9.4e-18	+0.58	4:184649399:T:C
Adipose Subcutaneous	eqtl	4.5e-17	-0.30	4:184567662:G:T
Breast Mammary Tissue	sqtl	2.1e-16	+0.97	4:184648576:C:T
Skin Sun Exposed Lower leg	sqtl	3.5e-16	+0.69	4:184648576:C:T
Whole Blood	eqtl	2.1e-15	-0.20	4:184668747:C:A
Esophagus Gastroesophageal Junction	sqtl	4.6e-14	+0.90	4:184648576:C:T

FANTOM5 promoters

1 alternative TSS:

Promoter ID	TPM avg	Samples expressed
55151	43.2886	1808

Top tissues by expression

showing 100 of 277 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
jejunal mucosa	UBERON:0000399	95.17	gold quality
rectum	UBERON:0001052	93.30	gold quality
epithelium of nasopharynx	UBERON:0001951	92.51	silver quality
nasopharynx	UBERON:0001728	92.49	silver quality
ventricular zone	UBERON:0003053	92.23	gold quality
duodenum	UBERON:0002114	92.09	gold quality
palpebral conjunctiva	UBERON:0001812	91.76	gold quality
monocyte	CL:0000576	91.46	gold quality
esophagus squamous epithelium	UBERON:0006920	91.43	gold quality
mononuclear cell	CL:0000842	91.17	gold quality
leukocyte	CL:0000738	91.03	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	90.54	gold quality
ganglionic eminence	UBERON:0004023	90.41	gold quality
colonic mucosa	UBERON:0000317	90.31	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	90.22	gold quality
mucosa of sigmoid colon	UBERON:0004993	90.17	gold quality
vermiform appendix	UBERON:0001154	90.00	gold quality
mucosa of transverse colon	UBERON:0004991	90.00	gold quality
cortical plate	UBERON:0005343	89.48	gold quality
lymph node	UBERON:0000029	89.31	gold quality
gall bladder	UBERON:0002110	89.00	gold quality
esophagus mucosa	UBERON:0002469	88.93	gold quality
adrenal tissue	UBERON:0018303	88.87	gold quality
eye	UBERON:0000970	88.67	gold quality
oral cavity	UBERON:0000167	88.41	gold quality
nasal cavity mucosa	UBERON:0001826	88.00	gold quality
secondary oocyte	CL:0000655	87.94	gold quality
calcaneal tendon	UBERON:0003701	87.94	gold quality
nasal cavity epithelium	UBERON:0005384	87.86	silver quality
transverse colon	UBERON:0001157	87.71	gold quality
bone marrow	UBERON:0002371	87.62	gold quality
embryo	UBERON:0000922	87.25	gold quality
islet of Langerhans	UBERON:0000006	86.82	gold quality
tonsil	UBERON:0002372	86.68	gold quality
spleen	UBERON:0002106	86.61	gold quality
caecum	UBERON:0001153	86.59	gold quality
amniotic fluid	UBERON:0000173	86.56	gold quality
cerebellar hemisphere	UBERON:0002245	86.52	gold quality
cerebellar cortex	UBERON:0002129	86.44	gold quality
bone element	UBERON:0001474	86.33	gold quality
granulocyte	CL:0000094	86.31	gold quality
epithelium of esophagus	UBERON:0001976	86.31	gold quality
small intestine	UBERON:0002108	86.29	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	86.26	gold quality
small intestine Peyer’s patch	UBERON:0003454	86.23	gold quality
right lobe of liver	UBERON:0001114	86.17	gold quality
intestine	UBERON:0000160	86.03	gold quality
stromal cell of endometrium	CL:0002255	85.93	gold quality
large intestine	UBERON:0000059	85.78	gold quality
bone marrow cell	CL:0002092	85.73	gold quality
placenta	UBERON:0001987	85.55	gold quality
right hemisphere of cerebellum	UBERON:0014890	85.54	gold quality
colon	UBERON:0001155	85.52	gold quality
esophagus	UBERON:0001043	85.36	gold quality
jejunum	UBERON:0002115	85.35	gold quality
lower esophagus mucosa	UBERON:0035834	85.24	gold quality
body of stomach	UBERON:0001161	84.92	gold quality
cerebellum	UBERON:0002037	84.87	gold quality
endometrium	UBERON:0001295	84.83	gold quality
bronchial epithelial cell	CL:0002328	84.72	gold quality
smooth muscle tissue	UBERON:0001135	84.60	gold quality
mucosa of stomach	UBERON:0001199	84.53	gold quality
gastrocnemius	UBERON:0001388	84.49	gold quality
colonic epithelium	UBERON:0000397	84.32	gold quality
blood	UBERON:0000178	84.14	gold quality
muscle of leg	UBERON:0001383	84.02	gold quality
tendon	UBERON:0000043	83.92	gold quality
stomach	UBERON:0000945	83.90	gold quality
minor salivary gland	UBERON:0001830	83.90	gold quality
trabecular bone tissue	UBERON:0002483	83.80	gold quality
gingival epithelium	UBERON:0001949	83.73	silver quality
right adrenal gland cortex	UBERON:0035827	83.71	gold quality
mouth mucosa	UBERON:0003729	83.68	gold quality
epithelium of bronchus	UBERON:0002031	83.63	gold quality
gingiva	UBERON:0001828	83.55	silver quality
pancreas	UBERON:0001264	83.54	gold quality
sigmoid colon	UBERON:0001159	83.48	gold quality
left adrenal gland	UBERON:0001234	83.38	gold quality
right adrenal gland	UBERON:0001233	83.36	gold quality
bronchus	UBERON:0002185	83.22	gold quality
mucosa of urinary bladder	UBERON:0001259	83.14	silver quality
thoracic aorta	UBERON:0001515	83.02	gold quality
adrenal gland	UBERON:0002369	82.99	gold quality
ascending aorta	UBERON:0001496	82.92	gold quality
mucosa of paranasal sinus	UBERON:0005030	82.92	silver quality
left adrenal gland cortex	UBERON:0035825	82.86	gold quality
body of pancreas	UBERON:0001150	82.80	gold quality
omental fat pad	UBERON:0010414	82.78	gold quality
peritoneum	UBERON:0002358	82.75	gold quality
hindlimb stylopod muscle	UBERON:0004252	82.57	gold quality
right coronary artery	UBERON:0001625	82.51	gold quality
left uterine tube	UBERON:0001303	82.20	gold quality
adrenal cortex	UBERON:0001235	82.17	gold quality
visceral pleura	UBERON:0002401	82.08	gold quality
adipose tissue of abdominal region	UBERON:0007808	82.07	gold quality
muscle layer of sigmoid colon	UBERON:0035805	81.98	gold quality
left coronary artery	UBERON:0001626	81.94	gold quality
vagina	UBERON:0000996	81.93	gold quality
urinary bladder	UBERON:0001255	81.91	gold quality
parietal pleura	UBERON:0002400	81.91	gold quality

Single-cell (SCXA)

Detected in 5 experiment(s), a significant marker in 4.

Experiment	Marker?	Max mean expression
E-MTAB-7008	yes	1734.58
E-MTAB-11121	yes	1081.99
E-CURD-46	yes	18.11
E-CURD-88	no	3.64
E-ANND-3	no	0.00

HPA expression

RNA tissue specificity: Low tissue specificity

showing 60 of 79 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Duodenum	tissue	47.5	medium
Tonsil	tissue	36.6	medium
Small intestine	tissue	36.3	medium
Lymph node	tissue	35.8	medium
Thymus	tissue	33.6
Colon	tissue	29.8	medium
Rectum	tissue	28.1	medium
Stomach 1	tissue	26.1	medium
Esophagus	tissue	25.0	low
Placenta	tissue	23.2	medium
Urinary bladder	tissue	22.0	medium
Appendix	tissue	22.0	medium
Liver	tissue	18.7	not detected
Spleen	tissue	17.5	medium
Frontal cortex	tissue	15.7
Gallbladder	tissue	15.7	low
Bone marrow	tissue	13.3	medium
Heart muscle	tissue	12.7	not detected
Skin 1	tissue	12.6	not detected
Adipose tissue	tissue	12.6	not detected
Breast	tissue	12.5	not detected
Smooth muscle	tissue	12.5	not detected
Tongue	tissue	12.2
Pancreas	tissue	11.6	low
Cervix	tissue	11.5	not detected
Vagina	tissue	11.4	not detected
Endometrium 1	tissue	10.7	medium
Superior colliculi	tissue	10.2
Lung	tissue	9.8	low
Prostate	tissue	9.7	not detected
Ovary	tissue	9.5	low
Caudate putamen	tissue	9.5
Seminal vesicle	tissue	9.4	medium
Adrenal gland	tissue	9.3	not detected
Epididymis	tissue	8.9	not detected
Olfactory bulb	tissue	8.8
Thyroid gland	tissue	8.7	low
Cerebral cortex	tissue	8.5	not detected
Hippocampal formation	tissue	8.5
Temporal cortex	tissue	8.5
Pituitary gland	tissue	8.4
Retina	tissue	8.2
Parathyroid gland	tissue	7.9	not detected
Testis	tissue	7.8	medium
Fallopian tube	tissue	7.7	not detected
Kidney	tissue	7.5	not detected
Spinal cord	tissue	7.4
Amygdala	tissue	7.3
Thalamus	tissue	7.3
Hippocampus	tissue	7.3	low
Somatosensory cortex	tissue	7.3
Entorhinal cortex	tissue	7.2
Motor cortex	tissue	7.1
Retrosplenial and cingulate cortex	tissue	7.1
Salivary gland	tissue	7.0	not detected
Occipital cortex	tissue	7.0
Midbrain	tissue	6.9
Nucleus accumbens	tissue	6.7
Skeletal muscle	tissue	6.6	not detected
Retrosplenial cortex	tissue	6.6

Brain sub-regions (HPA Brain Atlas): detected in 190; highest nTPM — Cerebellar cortex (16.7), Flocculonodular lobe (16.3), Vermis (14.8), Blood vessel (10.6), Dorsal funiculus (white matter) (9.8).

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): ANXA3, AR, ATF2, CEBPD, CTNNB1, DDIT3, DEAF1, DLL4, E2F1, EHF, ENO1, ETS1, EWSR1, FLI1, FOXO1, FOXO3, FOXP3, GATA2, HIF1A, ING1, ING4, JUN, LMX1B, NFKB1, NKX3-1, NOTCH1, PARP1, PHF10, PML, POU1F1, PPARA, PROP1, RBM10, RBPJ, RELA, ROCK1, RUNX3, SIM2, SLC22A2, SMAD5

miRNA regulators (miRDB)

Targeting CASP3 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 98 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-29A-3P	100.00	73.11	1835
HSA-MIR-29B-3P	100.00	73.18	1833
HSA-MIR-29C-3P	100.00	73.15	1833
HSA-MIR-4533	100.00	69.48	2758
HSA-MIR-4500	99.99	72.72	2367
HSA-MIR-1184	99.99	68.19	1458
HSA-MIR-511-3P	99.99	68.85	1467
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-LET-7A-5P	99.98	72.29	1790
HSA-LET-7B-5P	99.98	72.31	1790
HSA-LET-7C-5P	99.98	72.29	1790
HSA-LET-7E-5P	99.98	72.29	1790
HSA-LET-7F-5P	99.98	72.56	1784
HSA-LET-7G-5P	99.98	72.37	1784
HSA-LET-7I-5P	99.98	72.37	1788
HSA-MIR-98-5P	99.98	72.33	1787
HSA-MIR-103A-3P	99.98	69.14	1595
HSA-MIR-107	99.98	69.14	1595
HSA-MIR-3688-3P	99.97	72.02	2834
HSA-LET-7D-5P	99.96	71.76	1632
HSA-MIR-4458	99.96	71.64	1650
HSA-MIR-548AT-5P	99.96	70.83	2666
HSA-LET-7C-3P	99.95	73.42	2862
HSA-MIR-101-3P	99.94	75.03	2230
HSA-MIR-4760-3P	99.93	70.50	2385
HSA-MIR-7-1-3P	99.91	71.53	4384

Functional genomics

gnomAD constraint: pLI 0.0669, LOEUF 0.859, missense Z 1.49 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD RMC): no regional variation along ENST00000308394 — one region, missense o/e 0.79.

Literature-anchored findings (GeneRIF, showing 40)

• A soluble proform of caspase 3 containing a fortuitous mutation (W206R) is inactive when incubated with recombinant human caspase 8 and therefore can serve as a useful reagent to test the efficacy of caspase 8 inhibitors. (PMID:11437602)
• Enzyme activation of caspase-3 was observed in apoptosis of K562 human cell line. (PMID:11787859)
• caspase-3 may participate in the regulation mechanism of lymphoma cel apoptosis. (PMID:11866986)
• Activation of caspase-3 and cleavage of Rb are associated with p16-mediated apoptosis in human non-small cell lung cancer cells. (PMID:11960384)
• caspase 3-mediated focal adhesion kinase processing in human ovarian cancer cells: possible regulation by X-linked inhibitor of apoptosis protein (PMID:11972398)
• investigation of molecular mechanism of MPO-mediated apoptosis and caspase-3 activation (PMID:11981455)
• These data suggest that D4-GDI of Rho family GTPase may be regulated during apoptosis through the caspase-3 mediated cleavage of the GDI protein. (PMID:11989976)
• Clinical significance of caspase-3 expression in pathologic-stage I, nonsmall-cell lung cancer (PMID:11992386)
• translation of some IRES-containing mRNAs is regulated by proteolytic cleavage of PTB during apoptosis (PMID:12004072)
• results suggest that IGF-1/PI-3 kinase inhibited C2-ceramide-induced apoptosis due to relieving oxidative damage, which resulted from the inhibition of catalase by activated caspase-3 (PMID:12032677)
• Expression levels of apoptosis-related proteins caspase 3, Bcl-2, and PI9 predict clinical outcome in anaplastic large cell lymphoma. (PMID:12036886)
• Identification of high caspase-3 mRNA expression as a unique signature profile for extremely old individuals (PMID:12044963)
• The significant expression of caspase-3 that occurs in monocytes during serum-deprived induction of apoptosis can be down-regulated to baseline levels by addition of platelets. (PMID:12055227)
• High numbers of active caspase 3-positive Reed-Sternberg cells in pretreatment biopsy specimens of patients with Hodgkin disease predict favorable clinical outcome. (PMID:12070005)
• Caspase-cleaved amyloid precursor protein and activated caspase-3 are co-localized in the granules of granulovacuolar degeneration in Alzheimer’s disease and Down’s syndrome brain. (PMID:12070657)
• Selective inhibition of dipeptidyl peptidase I, not caspases, prevents the partial processing of procaspase-3 in CD3-activated human CD8(+) T lymphocytes (PMID:12080079)
• Pro-CASP3 moved to the the mitochondria of U937 cells during TPA-induced differentiation. (PMID:12145703)
• caspase 3 cleaves CDC6 during apoptosis, which prevents wounded cell from replicating and facilitates death (PMID:12151338)
• Both oleandrin and radiation share a caspase-3 dependent mechanism of apoptosis in the PC-3 human prostate cacncer cell line. (PMID:12169388)
• Hypoxia-induced cleavage of caspase-3 and DFF45/ICAD in human failed cardiomyocytes. (PMID:12181128)
• Role of nuclear PKC delta in mediating caspase-3-upregulation in Jurkat T leukemic cells exposed to ionizing radiation (PMID:12210761)
• Data show that endoplasmic reticulum stress induced by thapsigargin not only activated the apoptosis effector caspase-3 but also caused a large and prolonged increase in the activity of glycogen synthase kinase-3beta. (PMID:12228224)
• caspase 3-independent function of Bak in the TNF-alpha-induced apoptotic pathway (PMID:12297281)
• The apoptosis resistance of mdr cells is not related to the abnormality of CPP32 but the upstream of caspase, the fact of which indicates promising prospect of the research on reversion of mdr cells using CPP32 as target. (PMID:12390838)
• caspase 3 activation and apoptosis are blocked by LIGHT protein in hepatocytes (PMID:12393901)
• A significant positive correlation between in-situ active caspase-3 in the sperm midpiece and DNA fragmentation was observed in the low motility fractions of patients. (PMID:12397210)
• IFN-gamma-mediated caspase-3 activation and C. burnetii killing depend on the expression of membrane TNF. (PMID:12444137)
• determination of levels of caspase-3 expression in breast tumor samples and to determine whether alterations in its expression can affect their ability to undergo apoptosis (PMID:12483536)
• ceramide increases oxidative damage by inhibition of ROS scavenging ability through caspase-3-dependent proteolysis of catalase (PMID:12511568)
• caspase 3 has a role in damaging mitochondrial function and generating reactive oxygen species after activation by cytochrome c (PMID:12515825)
• Presentation of nitric oxide regulates monocyte survival through effects on this enzyme and caspase-9 activation. (PMID:12566444)
• induction of ceramide accumulation by various triggers of ceramide generation triggered the activation of caspase-3. (PMID:12576296)
• mRNA and protein expression of this enzyme are examined in breast cancer to determine level of apoptosis. (PMID:12576443)
• CASP3 induced by H202 was completely blocked by Z-VAD-fmk. (PMID:12579342)
• caspase-3 is essential for efficient induction of apoptosis by staurosporine, but not for mitochondrial steps that occur earlier in the pathway (PMID:12581734)
• one or more distinct cellular mechanisms regulate Bid cleavage by caspases 8 and 3 in situ. (PMID:12598529)
• caspase-3 was upregulated in a region-specific manner with marked activation in the selectively vulnerable hippocampal after cerebral ischemia (PMID:12605885)
• Data report that human oocytes and fragmenting preimplantation embryos possess transcripts encoding Harakiri and caspase-3. (PMID:12606589)
• caspase-3-mediated proteolysis of FAK, an anti-apoptotic protein, is regulated by hsp72 (PMID:12611892)
• in neutrophils, functional expression of caspase-3 in neutrophils may be regulated during ontogeny. (PMID:12621124)

Cross-species orthologs

9 orthologs

Organism	Symbol	Gene ID
danio_rerio	casp3a	ENSDARG00000017905
danio_rerio	casp3b	ENSDARG00000055045
mus_musculus	Casp3	ENSMUSG00000031628
rattus_norvegicus	Casp3	ENSRNOG00000010475
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), CASP7 (ENSG00000165806), PYDC1 (ENSG00000169900), CASP4 (ENSG00000196954), CARD16 (ENSG00000204397), CASP12 (ENSG00000204403), CARD18 (ENSG00000255501)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:107739) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 74 distinct phenotype terms.

Mouse phenotype (MP)	Records
cochlear ganglion degeneration	3
increased or absent threshold for auditory brainstem response	3
decreased inflammatory response	2
hydrocephaly	2
deafness	2
premature death	2
cochlear inner hair cell degeneration	2
cochlear outer hair cell degeneration	2
decreased apoptosis	2
prenatal lethality, incomplete penetrance	2
cochlear degeneration	1
abnormal organ of Corti morphology	1
delayed bone ossification	1
decreased bone mineral density	1
cleft palate	1
abnormal bone marrow development	1
decreased thymocyte number	1
abnormal forebrain morphology	1
abnormal olfactory bulb morphology	1
abnormal diencephalon morphology	1
abnormal cerebellum development	1
abnormal cerebellum external granule cell layer morphology	1
abnormal cerebellar granule layer morphology	1
abnormal cerebellar molecular layer	1
cranioschisis	1

+49 more (showing top 25).

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Bos taurus	O75601	100.0%	Diamond
Pan troglodytes	Q5IS54	99.6%	Diamond
Macaca fascicularis	Q2PFV2	96.0%	Diamond
Saimiri boliviensis boliviensis	Q5IS99	96.0%	Diamond
Mesocricetus auratus	Q60431	92.1%	Diamond
Oryctolagus cuniculus	Q8MJC3	90.6%	Diamond
Felis catus	Q8MJU1	89.9%	Diamond
Canis lupus familiaris	Q8MKI5	89.9%	Diamond
Sus scrofa	Q95ND5	88.8%	Diamond
Caenorhabditis remanei	P45436	84.5%	Diamond
Xenopus laevis	P55865	79.5%	Diamond
Equus caballus	Q9TV13	76.8%	Diamond
Gallus gallus	F1NV61	73.9%	Diamond
Spodoptera frugiperda	P89116	66.7%	Diamond
Macaca mulatta	Q153Z0	65.3%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
LINC02427	ncRNA	105377585
LINC02365	ncRNA	105377586
IRF2-DT	ncRNA	117134601
PRIMPOL	protein-coding	201973
CENPU	protein-coding	79682
ACSL1	protein-coding	2180
ACSL1-DT	ncRNA	105377587
MIR3945HG	ncRNA	731424
MIR3945	ncRNA	100500818
LINC01093	ncRNA	100506229

Protein

Protein identifiers

Caspase-3 — P42574 (reviewed: P42574)

Alternative names: Apopain, Cysteine protease CPP32, Protein Yama, SREBP cleavage activity 1

All UniProt accessions (4): A0A8V8TPU5, A8MVM1, C9JXR7, P42574

UniProt curated annotations — full annotation on UniProt →

Function. Thiol protease that acts as a major 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 many proteins. At the onset of apoptosis, it proteolytically cleaves poly(ADP-ribose) polymerase PARP1 at a ‘216-Asp-|-Gly-217’ bond. Cleaves and activates sterol regulatory element binding proteins (SREBPs) between the basic helix-loop-helix leucine zipper domain and the membrane attachment domain. Cleaves and activates caspase-6, -7 and -9 (CASP6, CASP7 and CASP9, respectively). Cleaves and inactivates interleukin-18 (IL18). Involved in the cleavage of huntingtin. Triggers cell adhesion in sympathetic neurons through RET cleavage. Also involved in axon pruning during brain development. Cleaves DSG2 in response to apoptosis resulting in a loss of full length DSG2 at desmosome cell junctions and subsequent loss of cell-cell adhesion. Also cleaves JUP in response to apoptosis. Cleaves and inhibits serine/threonine-protein kinase AKT1 in response to oxidative stress. 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. Also involved in pyroptosis by mediating cleavage and activation of gasdermin-E (GSDME). Cleaves XRCC4 and phospholipid scramblase proteins XKR4, XKR8 and XKR9, leading to promote phosphatidylserine exposure on apoptotic cell surface. Cleaves BIRC6 following inhibition of BIRC6-caspase binding by DIABLO/SMAC.

Subunit / interactions. Heterotetramer that consists of two anti-parallel arranged heterodimers, each one formed by a 17 kDa (p17) and a 12 kDa (p12) subunit. Interacts with BIRC6/bruce.

Subcellular location. Cytoplasm.

Tissue specificity. Highly expressed in lung, spleen, heart, liver and kidney. Moderate levels in brain and skeletal muscle, and low in testis. Also found in many cell lines, highest expression in cells of the immune system.

Post-translational modifications. Cleavage by granzyme B, caspase-6, caspase-8 and caspase-10 generates the two active subunits. Additional processing of the propeptides is likely due to the autocatalytic activity of the activated protease. Active heterodimers between the small subunit of caspase-7 protease and the large subunit of caspase-3 also occur and vice versa. S-nitrosylated on its catalytic site cysteine in unstimulated human cell lines and denitrosylated upon activation of the Fas apoptotic pathway, associated with an increase in intracellular caspase activity. Fas therefore activates caspase-3 not only by inducing the cleavage of the caspase zymogen to its active subunits, but also by stimulating the denitrosylation of its active site thiol. Ubiquitinated by BIRC6; this activity is inhibited by DIABLO/SMAC. (Microbial infection) ADP-riboxanation by C.violaceum CopC blocks CASP3 processing, preventing CASP3 activation and ability to recognize and cleave substrates.

Activity regulation. Inhibited by isatin sulfonamides. 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.

Similarity. Belongs to the peptidase C14A family.

RefSeq proteins (10): NP_001341706, NP_001341708, NP_001341709, NP_001341710, NP_001341711, NP_001341712, NP_001341713, NP_001427875, NP_004337, NP_116786 (=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 3.4.22.56 — caspase-3 (BRENDA: 15 organisms, 215 substrates, 504 inhibitors, 53 Km, 35 kcat entries)

Substrate kinetics (BRENDA)

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

Substrate	Km (mM)	Measurements
ACETYL-DEVD-7-AMIDO-4-METHYLCOUMARIN	0.005–10.7	10
ACETYL-L-ASP-L-GLU-L-VAL-L-ASP-7-AMIDO-4-METHYLC	0.0048–0.0335	6
BENZOYL-L-ASP-L-GLU-L-VAL-L-ASP-7-AMIDO-4-METHYL	0.002–0.0255	6
5’-TETRAMETHYLRHODAMINE-5(6)-CARBOXAMIDE-DEVD-CY	0.0016	1
AC-DEVD-4-METHYLCOUMARIN 7-AMIDE	0.0337	1
ACETYL-DEVD-4-NITROANILIDE	0.011	1
ACETYL-DQMD-4-NITROANILIDE	0.044	1
ACETYL-L-ASP-L-GLU-L-VAL-L-ASP-4-NITROANILIDE	0.067	1
ACETYL-L-ASP-L-MET-L-GLN-L-ASP-4-NITROANILIDE	1.6	1
ACETYL-L-ASP-L-VAL-L-ALA-L-ASP-4-NITROANILIDE	0.222	1
ACETYL-L-LEU-L-ASP-L-VAL-L-ALA-L-ASP-4-NITROANIL	0.147	1
ACETYL-L-VAL-L-ASP-L-VAL-L-ALA-L-ASP-4-NITROANIL	0.164	1
ACETYL-VDQMDGW-AMIDE	0.2	1
ACETYL-VDVAD-4-NITROANILIDE	0.067	1
ACETYL-VEID-4-NITROANILIDE	0.25	1

UniProt features (46 total): strand 13, helix 10, modified residue 5, turn 5, mutagenesis site 4, propeptide 2, sequence variant 2, chain 2, active site 2, sequence conflict 1

Structure

Experimental structures (PDB)

showing 30 of 135 structures by resolution:

PDB	Title	Method	Resolution (Å)
2DKO	Extended substrate recognition in caspase-3 revealed by high resolution X-ray structure …	X-RAY DIFFRACTION	1.06
2J32	The Role of Loop Bundle Hydrogen Bonds in the Maturation and Activity of(Pro)caspase-3	X-RAY DIFFRACTION	1.3
5IBP	Caspase 3 V266M	X-RAY DIFFRACTION	1.38
2J30	The Role of Loop Bundle Hydrogen Bonds in the Maturation and Activity of (Pro)caspase-3	X-RAY DIFFRACTION	1.4
4JJE	Caspase-3 specific unnatural amino acid peptides	X-RAY DIFFRACTION	1.48
4QUJ	Caspase-3 T140GV266H	X-RAY DIFFRACTION	1.5
2J31	The Role of Loop Bundle Hydrogen Bonds in the Maturation and Activity of(Pro)caspase-3	X-RAY DIFFRACTION	1.5
3PCX	Caspase-3 E246A, K242A Double Mutant	X-RAY DIFFRACTION	1.5
6CKZ	Human caspase-3 in complex with Ac-DW3-KE	X-RAY DIFFRACTION	1.5
6CL0	Human caspase-3 in complex with Ac-ATS009-KE	X-RAY DIFFRACTION	1.5
6X8I	Caspase-3 in complex with ketomethylene inhibitor reveals tetrahedral adduct	X-RAY DIFFRACTION	1.5
2XYG	Caspase-3:CAS329306	X-RAY DIFFRACTION	1.54
5IAS	Caspase 3 V266Y	X-RAY DIFFRACTION	1.54
6BFO	Caspase-3 Mutant- T245D	X-RAY DIFFRACTION	1.54
6BFJ	Caspase-3 Mutant - T245D,S249D	X-RAY DIFFRACTION	1.54
5IAE	Caspase 3 V266F	X-RAY DIFFRACTION	1.55
4QU9	Caspase-3 F128A	X-RAY DIFFRACTION	1.56
5IAJ	Caspase 3 V266L	X-RAY DIFFRACTION	1.58
4EHD	Allosteric Modulation of Caspase-3 through Mutagenesis	X-RAY DIFFRACTION	1.58
1NME	Structure of Casp-3 with tethered salicylate	X-RAY DIFFRACTION	1.6
6BGS	Caspase-3 Mutant - S150Y	X-RAY DIFFRACTION	1.6
4QTY	Caspase-3 E190A	X-RAY DIFFRACTION	1.6
6BHA	Caspase-3 Mutant - T152V	X-RAY DIFFRACTION	1.6
3EDQ	Crystal structure of Caspase-3 with inhibitor AC-LDESD-CHO	X-RAY DIFFRACTION	1.61
3PD1	Caspase-3 K242A	X-RAY DIFFRACTION	1.62
3ITN	Crystal structure of Pseudo-activated Procaspase-3	X-RAY DIFFRACTION	1.63
4PS0	Caspase-8 specific unnatural amino acid peptides	X-RAY DIFFRACTION	1.63
4EHF	Allosteric Modulation of Caspase-3 through Mutagenesis	X-RAY DIFFRACTION	1.66
5IBC	Caspase 3 V266I	X-RAY DIFFRACTION	1.66
4EHK	Allosteric Modulation of Caspase-3 through Mutagenesis	X-RAY DIFFRACTION	1.67

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P42574-F1	86.64	0.77

Human Protein Atlas

Protein class: Enzymes, ENZYME proteins, Hydrolases, Peptidases, Cysteine-type peptidases, Predicted intracellular proteins, Plasma proteins, Cancer-related genes, Candidate cancer biomarkers, FDA approved drug targets, Small molecule drugs

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): mitochondria; nucleoplasm

Antibody reliability (HPA): IH enhanced · IF approved

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)

Position	Role
121
163

Post-translational modifications (5)

Type	Positions
(microbial infection) adp-riboxanated arginine	207
N-acetylmethionine	1
N6-acetyllysine	11
Phosphoserine	26
S-nitrosocysteine	163

Mutagenesis-validated functional residues (4)

Position	Phenotype
9	in p3-d3a mutant; abolished cleavage and activation, leading to prevent thiol protease activity; when associated with a-28 and a-175.
28	in p3-d3a mutant; abolished cleavage and activation, leading to prevent thiol protease activity; when associated with a-9 and a-175.
175	in p3-d3a mutant; abolished cleavage and activation, leading to prevent thiol protease activity; when associated with a-9 and a-28.
207	abolished adp-riboxanation by c.violaceum copc.

Function

Pathways and Gene Ontology

Reactome pathways

12 curated (TAS) of 33; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

33 pathways:

ID	Pathway	Evidence
R-HSA-111459	Activation of caspases through apoptosome-mediated cleavage	curated
R-HSA-140342	Apoptosis induced DNA fragmentation	curated
R-HSA-351906	Apoptotic cleavage of cell adhesion proteins	curated
R-HSA-111465	Apoptotic cleavage of cellular proteins	curated
R-HSA-9960519	CASP4-mediated substrate cleavage	curated
R-HSA-9960525	CASP5-mediated substrate cleavage	curated
R-HSA-264870	Caspase-mediated cleavage of cytoskeletal proteins	curated
R-HSA-205025	NADE modulates death signalling	curated
R-HSA-449836	Other interleukin signaling	curated
R-HSA-5620971	Pyroptosis	curated
R-HSA-111469	SMAC, XIAP-regulated apoptotic response	curated
R-HSA-2028269	Signaling by Hippo	curated
R-HSA-109581	Apoptosis	—
R-HSA-75153	Apoptotic execution phase	—
R-HSA-111471	Apoptotic factor-mediated response	—
R-HSA-418889	Caspase activation via Dependence Receptors in the absence of ligand	electronic
R-HSA-5357769	Caspase activation via extrinsic apoptotic signalling pathway	—
R-HSA-204998	Cell death signalling via NRAGE, NRIF and NADE	—
R-HSA-111461	Cytochrome c-mediated apoptotic response	—
R-HSA-1280215	Cytokine Signaling in Immune system	—
R-HSA-73887	Death Receptor Signaling	—
R-HSA-1474228	Degradation of the extracellular matrix	electronic
R-HSA-1474244	Extracellular matrix organization	—
R-HSA-168256	Immune System	—
R-HSA-109606	Intrinsic Pathway for Apoptosis	—
R-HSA-5357801	Programmed Cell Death	—
R-HSA-5218859	Regulated Necrosis	—
R-HSA-111463	SMAC (DIABLO) binds to IAPs	electronic
R-HSA-111464	SMAC(DIABLO)-mediated dissociation of IAP:caspase complexes	electronic
R-HSA-162582	Signal Transduction	—
R-HSA-449147	Signaling by Interleukins	—
R-HSA-211736	Stimulation of the cell death response by PAK-2p34	electronic
R-HSA-193704	p75 NTR receptor-mediated signalling	—

MSigDB gene sets: 668 (showing top): GOBP_MYELOID_CELL_DIFFERENTIATION, GOBP_MORPHOGENESIS_OF_AN_EPITHELIUM, GOBP_REGULATION_OF_CELL_ACTIVATION, REACTOME_APOPTOSIS_INDUCED_DNA_FRAGMENTATION, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_REGULATION_OF_LEUKOCYTE_PROLIFERATION, GOBP_RESPONSE_TO_ETHANOL, GOBP_EMBRYO_DEVELOPMENT_ENDING_IN_BIRTH_OR_EGG_HATCHING, GOBP_RESPONSE_TO_IONIZING_RADIATION, GOBP_EPITHELIUM_DEVELOPMENT, GOBP_REGULATION_OF_AUTOPHAGY, GOBP_NEURON_RECOGNITION, REACTOME_INNATE_IMMUNE_SYSTEM, GOBP_COGNITION, GOBP_B_CELL_HOMEOSTASIS

GO Biological Process (52): luteolysis (GO:0001554), response to hypoxia (GO:0001666), negative regulation of cytokine production (GO:0001818), proteolysis (GO:0006508), apoptotic process (GO:0006915), axonal fasciculation (GO:0007413), learning or memory (GO:0007611), intrinsic apoptotic signaling pathway in response to osmotic stress (GO:0008627), response to xenobiotic stimulus (GO:0009410), response to glucose (GO:0009749), response to X-ray (GO:0010165), regulation of macroautophagy (GO:0016241), protein processing (GO:0016485), hippocampus development (GO:0021766), protein catabolic process (GO:0030163), neuron differentiation (GO:0030182), keratinocyte differentiation (GO:0030216), erythrocyte differentiation (GO:0030218), platelet formation (GO:0030220), regulation of protein stability (GO:0031647), response to cobalt ion (GO:0032025), response to estradiol (GO:0032355), response to lipopolysaccharide (GO:0032496), glial cell apoptotic process (GO:0034349), response to tumor necrosis factor (GO:0034612), response to nicotine (GO:0035094), swimming behavior (GO:0036269), response to hydrogen peroxide (GO:0042542), response to amino acid (GO:0043200), positive regulation of neuron apoptotic process (GO:0043525), response to ethanol (GO:0045471), neurotrophin TRK receptor signaling pathway (GO:0048011), striated muscle cell differentiation (GO:0051146), response to glucocorticoid (GO:0051384), protein maturation (GO:0051604), pyroptotic inflammatory response (GO:0070269), leukocyte apoptotic process (GO:0071887), response to anesthetic (GO:0072347), cellular response to staurosporine (GO:0072734), apoptotic signaling pathway (GO:0097190), intrinsic apoptotic signaling pathway (GO:0097193), execution phase of apoptosis (GO:0097194), regulation of synaptic vesicle cycle (GO:0098693), synapse pruning (GO:0098883), positive regulation of pyroptotic inflammatory response (GO:0140639), positive regulation of amyloid-beta formation (GO:1902004), response to insulin-like growth factor stimulus (GO:1990418), response to metal ion (GO:0010038), regulation of protein localization (GO:0032880), intracellular signal transduction (GO:0035556), positive regulation of apoptotic process (GO:0043065), regulation of neuron apoptotic process (GO:0043523)

GO Molecular Function (13): protease binding (GO:0002020), aspartic-type endopeptidase activity (GO:0004190), cysteine-type endopeptidase activity (GO:0004197), cyclin-dependent protein serine/threonine kinase inhibitor activity (GO:0004861), death receptor binding (GO:0005123), enzyme activator activity (GO:0008047), peptidase activity (GO:0008233), phospholipase A2 activator activity (GO:0016005), protein-containing complex binding (GO:0044877), endopeptidase activity (GO:0004175), protein binding (GO:0005515), cysteine-type peptidase activity (GO:0008234), hydrolase activity (GO:0016787)

GO Cellular Component (8): nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), cytosol (GO:0005829), postsynaptic density (GO:0014069), death-inducing signaling complex (GO:0031264), neuronal cell body (GO:0043025), glutamatergic synapse (GO:0098978)

Reactome top-level categories

14 top-level categories:

Category	Pathways
Apoptotic execution phase	3
SMAC, XIAP-regulated apoptotic response	2
Apoptotic factor-mediated response	2
Apoptotic cleavage of cellular proteins	2
Non-canonical inflammasome activation	2
Cytochrome c-mediated apoptotic response	1
Extracellular matrix organization	1
Signal Transduction	1
Cell death signalling via NRAGE, NRIF and NADE	1
Caspase activation via extrinsic apoptotic signalling pathway	1
Signaling by Interleukins	1
Regulated Necrosis	1
Programmed Cell Death	1
Apoptosis	1

GO top-level categories

showing 60 of 67 GO namespaces:

Category	Terms
cellular anatomical structure	3
protein metabolic process	2
myeloid cell differentiation	2
endopeptidase activity	2
catalytic activity	2
binding	2
peptidase activity	2
female gonad development	1
ovulation cycle process	1
response to stress	1
response to decreased oxygen levels	1
cytokine production	1
regulation of cytokine production	1
negative regulation of gene expression	1
negative regulation of multicellular organismal process	1
programmed cell death	1
apoptotic signaling pathway	1
execution phase of apoptosis	1
neuron recognition	1
axon development	1
neuron projection fasciculation	1
behavior	1
cognition	1
cellular response to osmotic stress	1
intrinsic apoptotic signaling pathway	1
response to chemical	1
response to hexose	1
response to ionizing radiation	1
regulation of autophagy	1
macroautophagy	1
proteolysis	1
protein maturation	1
pallium development	1
limbic system development	1
animal gross anatomical part developmental process	1
macromolecule catabolic process	1
cell differentiation	1
generation of neurons	1
epidermal cell differentiation	1
skin development	1
erythrocyte homeostasis	1
platelet morphogenesis	1
anatomical structure formation involved in morphogenesis	1
regulation of biological quality	1
enzyme binding	1
aspartic-type peptidase activity	1
cysteine-type peptidase activity	1
cyclin-dependent protein serine/threonine kinase activity	1
cyclin-dependent protein serine/threonine kinase regulator activity	1
protein serine/threonine kinase inhibitor activity	1
tumor necrosis factor receptor superfamily binding	1
enzyme regulator activity	1
molecular function activator activity	1
hydrolase activity	1
catalytic activity, acting on a protein	1
A2-type glycerophospholipase activity	1
phospholipase activator activity	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
intracellular anatomical structure	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 20 of 73 annotations. The rest are phylogenetic / computational / electronic (IEA).

20 experimentally-supported GO terms:

GO term	NS	Evidence
apoptotic process	BP	direct assay
cellular response to staurosporine	BP	mutant phenotype
erythrocyte differentiation	BP	direct assay
execution phase of apoptosis	BP	direct assay
intrinsic apoptotic signaling pathway	BP	mutant phenotype
negative regulation of cytokine production	BP	mutant phenotype
neurotrophin TRK receptor signaling pathway	BP	direct assay
positive regulation of amyloid-beta formation	BP	direct assay
positive regulation of pyroptotic inflammatory response	BP	direct assay
protein catabolic process	BP	direct assay
protein maturation	BP	direct assay
protein processing	BP	direct assay
proteolysis	BP	direct assay
pyroptotic inflammatory response	BP	direct assay
regulation of protein stability	BP	direct assay
cytoplasm	CC	direct assay
cytosol	CC	direct assay
nucleus	CC	direct assay
cysteine-type endopeptidase activity	MF	direct assay
peptidase activity	MF	direct assay

Protein interactions and networks

STRING

showing 15 of 7,530 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CASP3	CYCS	P00001	978
CASP3	BCL2	P10415	975
CASP3	BAX	P55269	970
CASP3	PARP1	P09874	940
CASP3	TP53	P04637	932
CASP3	APAF1	O14727	932
CASP3	BCL2L1	Q07817	932
CASP3	TNF	P01375	928
CASP3	PXDN	Q92626	921
CASP3	PXDNL	A1KZ92	921
CASP3	ANXA5	P08758	920
CASP3	IL1B	P01584	918
CASP3	AKT1	P31749	915
CASP3	XIAP	P98170	905
CASP3	CASP9	P55211	893

IntAct

Human interaction partners of CASP3 in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

showing 30 of 61 partners by confidence:

Partner	Interaction type	MIscore	Records
XIAP	physical association	0.870	6
TXN	physical association	0.750	6
APP	physical association	0.660	4
APAF1	cleavage reaction	0.650	7
CASP9	cleavage reaction	0.640	4
PARP1	protein cleavage	0.620	2
NMT2	protein cleavage	0.610	2
MDM2	protein cleavage	0.570	3
AKT3	proximity	0.570	2
CASP6	cleavage reaction	0.570	2
ATXN3	physical association	0.560	9
HTT	physical association	0.560	9
DCTN1	physical association	0.560	3
SOHLH1	physical association	0.560	3
YWHAG	physical association	0.550	1
AKAP8	physical association	0.520	5
WNK3	physical association	0.520	2
GATA1	colocalization	0.490	2
CDC42	proximity	0.480	1
PANX1	protein cleavage	0.440	2
AKT1	cleavage reaction	0.440	1
AKT2	cleavage reaction	0.440	1
ARHGDIB	cleavage reaction	0.440	1
ATG16L1	protein cleavage	0.440	1
BID	cleavage reaction	0.440	1
CALB1	direct interaction	0.440	1
CASP8	direct interaction	0.440	1
CRYAB	direct interaction	0.440	1
E1	direct interaction	0.440	1
GSDME	protein cleavage	0.440	1

BioGRID (239 interactions; top human partners by supporting records): XIAP (Affinity Capture-MS; 32 records), BIRC6 (Biochemical Activity; 8 records), PARP1 (Biochemical Activity; 8 records), BIRC2 (Reconstituted Complex; 5 records), CASP9 (Co-localization; 5 records), CDKN1A (Co-localization; 5 records), CRYAB (Affinity Capture-Western; 5 records), MDM2 (Co-localization; 4 records), BIRC5 (Reconstituted Complex; 3 records), CASP6 (Co-localization; 3 records), CASP8 (Biochemical Activity; 3 records), CFLAR (Affinity Capture-Western; 3 records), HCLS1 (Co-localization; 3 records), HSPD1 (Affinity Capture-Western; 3 records), MAPT (Biochemical Activity; 3 records)

SIGNOR signaling

showing 47 of 76 signaling interactions:

A	Effect	B	Mechanism
CASP3	“down-regulates activity”	PTCH1	cleavage
CASP3	up-regulates	ROCK1	cleavage
XIAP	“down-regulates quantity by destabilization”	CASP3	ubiquitination
XIAP	“down-regulates activity”	CASP3	binding
CASP3	down-regulates	IKBKB	cleavage
MAPK14	down-regulates	CASP3	phosphorylation
BIRC6	down-regulates	CASP3	binding
CASP3	“up-regulates activity”	BAD	cleavage
PPP2R5B	up-regulates	CASP3	dephosphorylation
CASP3	“up-regulates activity”	CASP9	cleavage
CASP9	“up-regulates activity”	CASP3	cleavage
CASP8	“up-regulates activity”	CASP3	cleavage
CASP3	down-regulates	PSIP1	cleavage
PAC-1	up-regulates	CASP3	“chemical activation”
CASP3	down-regulates	PTCH1	cleavage
ING1	“up-regulates quantity by expression”	CASP3	“transcriptional regulation”
CASP3	“down-regulates quantity by destabilization”	BRCA1	cleavage
CASP3	“down-regulates activity”	GSN	cleavage
“Caspase 9 complex”	“up-regulates activity”	CASP3	cleavage
“Caspase 8 complex”	“up-regulates activity”	CASP3	cleavage
Apoptosome	“up-regulates activity”	CASP3	cleavage
CASP3	up-regulates	Cell_death
RBM10	“down-regulates quantity by repression”	CASP3	“transcriptional regulation”
CASP3	“down-regulates quantity by destabilization”	GORASP1	cleavage
CASP3	“up-regulates activity”	GRIPAP1	cleavage
MYCT1	“up-regulates activity”	CASP3
ANXA3	“down-regulates quantity by repression”	CASP3	“transcriptional regulation”
CASP3	“down-regulates activity”	KDM4C	cleavage
RNF7	“down-regulates activity”	CASP3	ubiquitination
BCR-ABL	“down-regulates activity”	CASP3
CASP3	“down-regulates quantity by destabilization”	RAD51	cleavage
MAPKAPK2	“up-regulates activity”	CASP3	phosphorylation
CASP3	“up-regulates activity”	DFFA	cleavage
CASP3	up-regulates	DFFB	cleavage
CASP3	down-regulates	GSN	cleavage
CASP3	down-regulates	SPTAN1	cleavage
BIRC5	down-regulates	CASP3	binding
CASP3	up-regulates	CASP6	cleavage
CASP3	up-regulates	Chromatine_condensation
CASP3	up-regulates	DNA_fragmentation
CASP3	up-regulates	Membrane_blebbing
CASP3	up-regulates	ACIN1	cleavage
HSPB1	down-regulates	CASP3
CASP3	up-regulates	GAS2	cleavage
CASP3	up-regulates	Apoptosis
CASP3	“down-regulates activity”	PARP1	cleavage
STAT3	“up-regulates quantity by expression”	CASP3	“transcriptional regulation”

Protein complexes (CORUM) (2)

Experimentally-characterized complexes this protein is a subunit of (★ = the complex contains a known drug target).

2 complexes by size:

Complex	Subunits	Members
Aposome complex	4	APAF1, CASP3, CASP7, CASP9
Microaposome complex	2	CASP3, CASP7

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 61 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
Activation of BAD and translocation to mitochondria	6	86.2×	3e-09
Activation of BH3-only proteins	6	56.2×	5e-08
Intrinsic Pathway for Apoptosis	9	49.7×	2e-11
PI3K/AKT Signaling in Cancer	7	48.6×	6e-09
Constitutive Signaling by AKT1 E17K in Cancer	6	47.9×	1e-07
Apoptotic cleavage of cellular proteins	5	44.9×	3e-06
Apoptotic execution phase	5	44.9×	3e-06
FOXO-mediated transcription	7	44.4×	1e-08

GO biological processes:

GO term	Partners	Fold	FDR
response to estradiol	5	17.4×	1e-03
response to ethanol	5	12.8×	3e-03
positive regulation of apoptotic process	10	9.9×	2e-05
response to hypoxia	5	8.4×	8e-03
regulation of cell cycle	6	7.8×	4e-03
negative regulation of apoptotic process	12	7.3×	2e-05
intracellular signal transduction	10	6.7×	4e-04

Disease & clinical

Genetic variants

Variant evidence for CASP3: 28 ClinVar records (1 pathogenic / likely pathogenic); 3 GWAS associations. Per-variant detail is on Sugi Variant.

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	17
Likely benign	4
Benign	1

Top pathogenic / likely-pathogenic (1)

Showing all 1 pathogenic / likely-pathogenic ClinVar records, ranked by ClinVar review status (expert panel → multiple submitters → single submitter), then by number of submitting labs.

Variant ID	HGVS	Classification	Review	Submitters
562989	GRCh37/hg19 4q32.1-35.2(chr4:159492464-190957473)x3	Pathogenic	no assertion criteria provided	1

Per-variant reference — Sugi Variant

Explore CASP3’s pathogenic and likely-pathogenic variants individually — each with its ClinVar classification and conditions, applied ACMG criteria (ClinGen expert panel, where curated), the calibrated in-silico predictors (AlphaMissense, REVEL, SaProt, conservation), gnomAD frequency, and the predictor-disagreement QC signal — on Sugi Variant.

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 25 predictions of 608):

Position(s)	Effect	Δscore	Sites
4:184631165	acceptor_gain	1.0000
4:184631763–184631764	donor_loss	1.0000	4
4:184631941–184631942	acceptor_loss	1.0000	6
4:184631943	acceptor_gain	1.0000
4:184631951–184631953	acceptor_gain	1.0000	3
4:184631959	acceptor_gain	1.0000
4:184632266–184632267	donor_loss	1.0000	5
4:184632397	acceptor_loss	1.0000	2
4:184632398	acceptor_gain	1.0000
4:184635342	donor_gain	1.0000

AlphaMissense

854 missense substitutions predicted likely pathogenic (of 1,866 scored), across 187 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
M268	9	0.829	0.993
D70	8	0.995	0.998
H121	8	0.995	0.999
D192	8	0.989	0.997
D169	8	0.978	0.993
F55	8	0.972	1.000
F158	8	0.965	0.998
F78	8	0.955	0.992
F143	8	0.933	0.993
N52	8	0.911	0.996
H108	8	0.907	0.981
D68	8	0.881	0.952
F193	8	0.879	0.993
F114	8	0.839	0.989
W206	7	0.996	0.998
F215	7	0.996	0.998
W214	7	0.987	0.997
C163	7	0.980	0.996
D90	7	0.977	0.988
C148	7	0.974	0.995

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

Human Protein Atlas survival analysis — favorable = higher expression predicts better survival.

2 prognostic cancer types:

Cancer	Prognostic	p-value
Liver Hepatocellular Carcinoma (TCGA)	unfavorable	0.000454
Bladder Urothelial Carcinoma (TCGA)	favorable	0.000817

Disease associations

OMIM: gene MIM:600636 | disease phenotypes:

Genomics England panels (PanelApp)

Clinical diagnostic gene panels including this gene (1 panels, 1 green/diagnostic-grade). Confidence: green = diagnostic, amber = moderate.

1 panels:

Panel	Rating
COVID-19 research	green

GWAS associations

3 associations:

Study	Trait	p-value
GCST90013537_7	Kawasaki disease	1e-10
GCST010979_1	Kawasaki disease	2e-8
GCST006993_10	Hippocampal volume in Alzheimer’s disease dementia	2e-7

EFO canonical traits (from GWAS)

1 canonical traits:

EFO ID	Trait name
EFO:0005035	hippocampal volume

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (4): CHEMBL2334 (SINGLE PROTEIN), CHEMBL3430905 (PROTEIN FAMILY), CHEMBL3831289 (PROTEIN FAMILY), CHEMBL3885517 (PROTEIN COMPLEX)

Molecules with ChEMBL bioactivity

Phase ≥1, by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 15,943 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

5 molecules by phase:

Molecule	Name	Phase	Patents
CHEMBL41286	DIACEREIN	3	5,127
CHEMBL197672	EMRICASAN	2	1,564
CHEMBL165790	IPRIFLAVONE	2	5,493
CHEMBL437526	PRALNACASAN	2	1,421
CHEMBL591429	PAC-1	1	2,338

PharmGKB: 1 entry (CPIC guideline: no)

PharmGKB variant annotations

Per-publication pharmacogenomic findings for this gene (significant associations).

2 published findings:

Variant	Drug(s)	Category	Finding	PMID
rs2720376	cisplatin, doxorubicin	Efficacy	Allele C is associated with increased progression-free survival when treated with cisplatin and doxorubicin in people with Osteosarcoma as compared to allele T.	PMID:25829401
rs113420705	Immunoglobulins	Efficacy	Genotypes CT + TT are associated with decreased response to Immunoglobulins in children with Mucocutaneous Lymph Node Syndrome as compared to genotype CC.	PMID:21987091

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
Ac-DEVD-CHO	Inhibition	9.8	pIC50
M826	Inhibition	8.3	pKi
compound 4 [PMID: 12408711]	Inhibition	7.3	pKi
AZ10417808	Inhibition	6.61	pKi

Binding affinities (BindingDB)

1802 measured of 2104 human assays (2145 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
(S)-5-[(1,3-Dihydro-isoindol-2-ylmethyl)-amino]-3-(2-{3-[(4-methyl-furazan-3-ylmethyl)-amino]-2-oxo-2H-pyrazin-1-yl}-butyrylamino)-4-oxo-pentanoic acid	IC50	0.0087 nM
(S)-5-[(3,4-Dihydro-1H-isoquinolin-2-ylmethyl)-amino]-3-(2-{3-[(4-methyl-furazan-3-ylmethyl)-amino]-2-oxo-2H-pyrazin-1-yl}-butyrylamino)-4-oxo-pentanoic acid	IC50	0.013 nM
Ethyl 5-Amino-3-(4-methoxyphenyl)-4-oxo-3,4-dihydrothieno[3,4-d]pyridazine-1-carboxylate	EC50	0.0145 nM
(S)-3-(2-{5-Ethyl-3-[(4-methyl-furazan-3-ylmethyl)-amino]-2-oxo-2H-pyrazin-1-yl}-butyrylamino)-5-{[(hexyl-methyl-amino)-methyl]-amino}-4-oxo-pentanoic acid	IC50	0.025 nM
(S)-3-(2-{3-[(4-Methyl-furazan-3-ylmethyl)-amino]-2-oxo-2H-pyrazin-1-yl}-butyrylamino)-5-{[(methyl-octyl-amino)-methyl]-amino}-4-oxo-pentanoic acid	IC50	0.025 nM
(S)-5-{[(Hexyl-methyl-amino)-methyl]-amino}-3-(2-{3-[(4-methyl-furazan-3-ylmethyl)-amino]-2-oxo-2H-pyrazin-1-yl}-butyrylamino)-4-oxo-pentanoic acid	IC50	0.028 nM
(S)-5-{[(Butyl-methyl-amino)-methyl]-amino}-3-(2-{3-[(4-methyl-furazan-3-ylmethyl)-amino]-2-oxo-2H-pyrazin-1-yl}-butyrylamino)-4-oxo-pentanoic acid	IC50	0.031 nM
(S)-5-[(4-Benzyl-piperidin-1-ylmethyl)-amino]-3-(2-{3-[(4-methyl-furazan-3-ylmethyl)-amino]-2-oxo-2H-pyrazin-1-yl}-butyrylamino)-4-oxo-pentanoic acid	IC50	0.047 nM
(S)-3-(2-{3-[(4-Methyl-furazan-3-ylmethyl)-amino]-2-oxo-2H-pyrazin-1-yl}-butyrylamino)-5-{[(methyl-pentyl-amino)-methyl]-amino}-4-oxo-pentanoic acid	IC50	0.048 nM
[3-(2-{5-tert-Butyl-3-[(4-methyl-furazan-3-ylmethyl)-amino]-2-oxo-2H-pyrazin-1-yl}-butyrylamino)-4-carboxy-2-oxo-butyl]-hexyl-methyl-ammonium; chloride	IC50	0.05 nM
(S)-5-{[(Ethyl-methyl-amino)-methyl]-amino}-3-(2-{3-[(4-methyl-furazan-3-ylmethyl)-amino]-2-oxo-2H-pyrazin-1-yl}-butyrylamino)-4-oxo-pentanoic acid	IC50	0.056 nM
(S)-3-{(S)-2-[3-((S)-2-Acetylamino-3-carboxy-propionylamino)-2-oxo-2H-pyridin-1-yl]-butyrylamino}-5-benzylsulfanyl-4-oxo-pentanoic acid	IC50	0.06 nM
(S)-5-{[(Hexyl-methyl-amino)-methyl]-amino}-3-(2-{5-isopropyl-3-[(4-methyl-furazan-3-ylmethyl)-amino]-2-oxo-2H-pyrazin-1-yl}-butyrylamino)-4-oxo-pentanoic acid	IC50	0.063 nM
(S)-3-(2-{3-[(4-Methyl-furazan-3-ylmethyl)-amino]-2-oxo-2H-pyrazin-1-yl}-butyrylamino)-4-oxo-5-((S)-1-phenyl-ethylamino)-pentanoic acid	IC50	0.064 nM
(S)-5-Benzylsulfanyl-4-oxo-3-(2-{2-oxo-3-[(thiophen-2-ylmethyl)-amino]-2H-pyrazin-1-yl}-butyrylamino)-pentanoic acid	IC50	0.065 nM
(S)-3-(2-{5-tert-Butyl-3-[(4-methyl-furazan-3-ylmethyl)-amino]-2-oxo-2H-pyrazin-1-yl}-butyrylamino)-5-{[(hexyl-methyl-amino)-methyl]-amino}-4-oxo-pentanoic acid	IC50	0.067 nM
CHEMBL4751195	KI	0.08 nM
(S)-5-Benzylsulfanyl-3-(2-{3-[(2,3-dihydro-benzo[1,4]dioxin-2-ylmethyl)-amino]-2-oxo-2H-pyrazin-1-yl}-butyrylamino)-4-oxo-pentanoic acid	IC50	0.087 nM
[3-(2-{5-tert-Butyl-3-[(4-methyl-furazan-3-ylmethyl)-amino]-2-oxo-2H-pyrazin-1-yl}-butyrylamino)-4-carboxy-2-oxo-butyl]-methyl-pentyl-ammonium; chloride	IC50	0.11 nM
(S)-3-(2-{5-(1-Ethyl-1-methyl-propyl)-3-[(4-methyl-furazan-3-ylmethyl)-amino]-2-oxo-2H-pyrazin-1-yl}-butyrylamino)-5-{[(hexyl-methyl-amino)-methyl]-amino}-4-oxo-pentanoic acid	IC50	0.11 nM
(S)-3-(2-{5-tert-Butyl-3-[(4-methyl-furazan-3-ylmethyl)-amino]-2-oxo-2H-pyrazin-1-yl}-butyrylamino)-5-{[(methyl-pentyl-amino)-methyl]-amino}-4-oxo-pentanoic acid	IC50	0.11 nM
(S)-5-Benzylsulfanyl-4-oxo-3-(2-{2-oxo-3-[(thiazol-2-ylmethyl)-amino]-2H-pyrazin-1-yl}-butyrylamino)-pentanoic acid	IC50	0.13 nM
(S)-3-(2-{3-[(4-Methyl-furazan-3-ylmethyl)-amino]-2-oxo-2H-pyrazin-1-yl}-butyrylamino)-4-oxo-butyric acid	IC50	0.15 nM
(S)-5-Benzylsulfanyl-4-oxo-3-(2-{2-oxo-3-[(thiazol-5-ylmethyl)-amino]-2H-pyrazin-1-yl}-butyrylamino)-pentanoic acid	IC50	0.19 nM
(S)-5-Benzylsulfanyl-3-(2-{3-[(4-methyl-furazan-3-ylmethyl)-amino]-2-oxo-2H-pyrazin-1-yl}-butyrylamino)-4-oxo-pentanoic acid	IC50	0.22 nM
(S)-5-Benzylsulfanyl-3-{2-[3-(2-methyl-benzothiazol-5-ylamino)-2-oxo-2H-pyrazin-1-yl]-butyrylamino}-4-oxo-pentanoic acid	IC50	0.22 nM
(S)-5-Benzylsulfanyl-3-(2-{3-[(3-methyl-isoxazol-5-ylmethyl)-amino]-2-oxo-2H-pyrazin-1-yl}-butyrylamino)-4-oxo-pentanoic acid	IC50	0.23 nM
(S)-3-(2-{3-[(4-Methyl-furazan-3-ylmethyl)-amino]-2-oxo-2H-pyrazin-1-yl}-butyrylamino)-4-oxo-5-[(pyrrolidin-1-ylmethyl)-amino]-pentanoic acid	IC50	0.29 nM
(3S)-3-[(2S)-2-[(4S)-4-[(3S)-3-acetamido-3-formamidopropanoic acid]-4-formamidobutanoic acid]-3-methylbutanamido]-4-oxo-7-phenylheptanoic acid	IC50	0.31 nM
(S)-5-Benzylsulfanyl-3-(2-{3-[(isoxazol-3-ylmethyl)-amino]-2-oxo-2H-pyrazin-1-yl}-butyrylamino)-4-oxo-pentanoic acid	IC50	0.4 nM
(S)-3-(2-{3-[(4-Methyl-furazan-3-ylmethyl)-amino]-2-oxo-2H-pyrazin-1-yl}-butyrylamino)-4-oxo-4-(5-phenyl-oxazol-2-yl)-butyric acid	IC50	0.46 nM
(S)-3-(2-{5-tert-Butyl-3-[(4-methyl-furazan-3-ylmethyl)-amino]-2-oxo-2H-pyrazin-1-yl}-butyrylamino)-4-oxo-5-[(piperidin-1-ylmethyl)-amino]-pentanoic acid	IC50	0.62 nM
(S)-3-(2-{3-[(4-Methyl-furazan-3-ylmethyl)-amino]-2-oxo-2H-pyrazin-1-yl}-butyrylamino)-5-{[(methyl-propyl-amino)-methyl]-amino}-4-oxo-pentanoic acid	IC50	0.62 nM
(S)-5-Benzylsulfanyl-3-(2-{3-[(3-methyl-[1,2,4]oxadiazol-5-ylmethyl)-amino]-2-oxo-2H-pyrazin-1-yl}-butyrylamino)-4-oxo-pentanoic acid	IC50	0.67 nM
(S)-3-(2-{5-tert-Butyl-3-[(4-methyl-furazan-3-ylmethyl)-amino]-2-oxo-2H-pyrazin-1-yl}-butyrylamino)-5-[(morpholin-4-ylmethyl)-amino]-4-oxo-pentanoic acid	IC50	0.73 nM
(S)-5-[(7-Aza-bicyclo[2.2.1]hept-7-ylmethyl)-amino]-3-(2-{3-[(4-methyl-furazan-3-ylmethyl)-amino]-2-oxo-2H-pyrazin-1-yl}-butyrylamino)-4-oxo-pentanoic acid	IC50	0.88 nM
(S)-5-(Dimethylaminomethyl-amino)-3-(2-{3-[(4-methyl-furazan-3-ylmethyl)-amino]-2-oxo-2H-pyrazin-1-yl}-butyrylamino)-4-oxo-pentanoic acid	IC50	0.89 nM
(S)-5-Benzylsulfanyl-3-(2-{3-[2-(3-methyl-[1,2,4]oxadiazol-5-yl)-ethylamino]-2-oxo-2H-pyrazin-1-yl}-butyrylamino)-4-oxo-pentanoic acid	IC50	0.9 nM
(S)-5-Benzylsulfanyl-3-{2-[3-(3-methoxy-propylamino)-2-oxo-2H-pyrazin-1-yl]-butyrylamino}-4-oxo-pentanoic acid	IC50	0.92 nM
(S)-5-Benzylsulfanyl-4-oxo-3-(2-{2-oxo-3-[(5-phenyl-[1,3,4]oxadiazol-2-ylmethyl)-amino]-2H-pyrazin-1-yl}-butyrylamino)-pentanoic acid	IC50	0.98 nM
(S)-5-Benzylsulfanyl-4-oxo-3-{2-[2-oxo-3-(2-pyrazol-1-yl-ethylamino)-2H-pyrazin-1-yl]-butyrylamino}-pentanoic acid	IC50	0.99 nM
(4S,7S,11aS)-benzyl 4-(((3S)-2-hydroxy-5-oxo-tetrahydrofuran-3-yl)carbamoyl)-7-(2-naphthamido)-6-oxo-3,4,7,8,11,11a-hexahydro-1H-pyrazino[1,2-a]azocine-2(6H)-carboxylate	IC50	1 nM
(4S,7S,11aS)-N-((3S)-2-hydroxy-5-oxo-tetrahydrofuran-3-yl)-7-(isoquinoline-1-carboxamido)-6-oxo-2-(phenylsulfonyl)-decahydro-1H-pyrazino[1,2-a]azocine-4-carboxamide	IC50	1 nM
(4S,7S,11aS)-N-((3S)-2-hydroxy-5-oxo-tetrahydrofuran-3-yl)-7-(isoquinoline-1-carboxamido)-6-oxo-decahydro-[1,4]oxazino[4,3-a]azocine-4-carboxamide	IC50	1 nM
(4S,7S,11aS)-benzyl 4-(((3S)-2-hydroxy-5-oxo-tetrahydrofuran-3-yl)carbamoyl)-7-benzamido-6-oxo-3,4,7,8,11,11a-hexahydro-1H-pyrazino[1,2-a]azocine-2(6H)-carboxylate	IC50	1 nM
(4S,7S,11aS)-N-((3S)-2-hydroxy-5-oxo-tetrahydrofuran-3-yl)-7-(isoquinoline-1-carboxamido)-6-oxo-decahydro-1H-pyrazino[1,2-a]azocine-4-carboxamide	IC50	1 nM
(4S,7S,11aS)-7-(2-naphthamido)-N-((3S)-2-hydroxy-5-oxo-tetrahydrofuran-3-yl)-6-oxo-decahydro-1H-pyrazino[1,2-a]azocine-4-carboxamide	IC50	1 nM
(4S,7S,11aS)-benzyl 4-(((3S)-2-hydroxy-5-oxo-tetrahydrofuran-3-yl)carbamoyl)-7-(isoquinoline-1-carboxamido)-6-oxo-3,4,7,8,11,11a-hexahydro-1H-pyrazino[1,2-a]azocine-2(6H)-carboxylate	IC50	1 nM
(4S,7S,11aS)-7-(benzo[b]thiophene-2-carboxamido)-N-((3S)-2-hydroxy-5-oxo-tetrahydrofuran-3-yl)-6-oxo-decahydro-[1,4]oxazino[4,3-a]azocine-4-carboxamide	IC50	1 nM
(4S,7S,11aS)-7-(2-naphthamido)-N-((3S)-2-hydroxy-5-oxo-tetrahydrofuran-3-yl)-6-oxo-decahydro-[1,4]oxazino[4,3-a]azocine-4-carboxamide	IC50	1 nM

ChEMBL bioactivities

1591 potent at pChembl≥5 of 2367 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
10.10	Ki	0.08	nM	CHEMBL4751195
10.00	IC50	0.1	nM	CHEMBL180669
9.70	IC50	0.2	nM	CHEMBL417149
9.70	Ki	0.2	nM	CHEMBL213759
9.64	Ki	0.23	nM	CHEMBL5723373
9.52	IC50	0.3	nM	CHEMBL178116
9.52	IC50	0.3	nM	CHEMBL213759
9.30	EC50	0.5	nM	CHEMBL456799
9.30	IC50	0.5	nM	CHEMBL456799
9.17	Ki	0.68	nM	CHEMBL5723360
9.11	IC50	0.771	nM	CHEMBL443565
9.10	IC50	0.8	nM	CHEMBL443565
9.10	Ki	0.8	nM	CHEMBL216071
9.00	Ki	1	nM	CHEMBL5641709
8.94	IC50	1.15	nM	CHEMBL3233630
8.92	Ki	1.2	nM	CHEMBL384023
8.92	Ki	1.2	nM	CHEMBL216819
8.92	Ki	1.2	nM	CHEMBL439753
8.92	IC50	1.2	nM	CHEMBL430648
8.89	IC50	1.29	nM	CHEMBL595807
8.86	IC50	1.38	nM	CHEMBL417149
8.85	Ki	1.4	nM	CHEMBL179503
8.80	IC50	1.6	nM	CHEMBL417149
8.77	IC50	1.7	nM	CHEMBL417149
8.77	IC50	1.7	nM	CHEMBL216071
8.74	IC50	1.8	nM	CHEMBL352426
8.72	Ki	1.9	nM	CHEMBL387041
8.70	EC50	2	nM	CHEMBL5289751
8.66	IC50	2.2	nM	CHEMBL417149
8.64	EC50	2.3	nM	CHEMBL456593
8.64	IC50	2.3	nM	CHEMBL100588
8.63	IC50	2.32	nM	CHEMBL594384
8.62	IC50	2.4	nM	CHEMBL216819
8.62	IC50	2.4	nM	CHEMBL384023
8.62	IC50	2.4	nM	CHEMBL293034
8.62	IC50	2.4	nM	CHEMBL606626
8.60	IC50	2.5	nM	CHEMBL439753
8.59	IC50	2.6	nM	CHEMBL3359197
8.54	IC50	2.9	nM	CHEMBL3359202
8.52	IC50	3	nM	CHEMBL420407
8.52	IC50	3	nM	CHEMBL2086889
8.52	IC50	3	nM	CHEMBL60671
8.52	IC50	2.999	nM	CHEMBL60671
8.51	IC50	3.1	nM	CHEMBL3133146
8.51	IC50	3.1	nM	CHEMBL60671
8.51	IC50	3.1	nM	CHEMBL1762353
8.49	Ki	3.2	nM	CHEMBL225647
8.48	IC50	3.3	nM	CHEMBL603644
8.48	IC50	3.3	nM	CHEMBL1762350
8.46	IC50	3.5	nM	CHEMBL430648

PubChem BioAssay actives

1568 with measured affinity, of 2710 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-carboxypropanoyl]amino]-5-[[(2S)-1-[[(2S)-1-carboxy-4-[[2-[4-(dimethylamino)phenyl]-1,3-benzoxazol-5-yl]amino]-3-oxobutan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]amino]-5-oxopentanoic acid	1674214: Inhibition of caspase-3 (unknown origin) using Ac-DEVD-AMCA as substrate incubated for 5 mins by Dixon plot analysis	ki	0.0001	uM
(3S)-3-[2-[5-tert-butyl-3-[(4-methyl-1,2,5-oxadiazol-3-yl)methylamino]-2-oxopyrazin-1-yl]butanoylamino]-5-[[methyl(pentyl)amino]methylamino]-4-oxopentanoic acid	241557: Inhibitory concentration against recombinant human caspase-3 in neuronal precursor (NT2) cells	ic50	0.0001	uM
1-[[4-(2-fluoroethoxy)phenyl]methyl]-5-[(2S)-2-(phenoxymethyl)pyrrolidin-1-yl]sulfonylindole-2,3-dione	271887: Binding affinity to human caspase 3	ki	0.0002	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	1795223: Fluorometric Assay from Article 10.1074/jbc.273.49.32608: “Inhibition of human caspases by peptide-based and macromolecular inhibitors.”	ki	0.0002	uM
(3S)-3-[[(2S)-2-[3-[[(2S)-2-acetamido-3-carboxypropanoyl]amino]-2-oxo-1-pyridinyl]butanoyl]amino]-5-benzylsulfanyl-4-oxopentanoic acid	241557: Inhibitory concentration against recombinant human caspase-3 in neuronal precursor (NT2) cells	ic50	0.0003	uM
5-[(2S)-2-[(2,4-difluorophenoxy)methyl]pyrrolidin-1-yl]sulfonyl-1-[[1-(2-fluoroethyl)triazol-4-yl]methyl]indole-2,3-dione	389836: Inhibition of human recombinant caspase 3 assessed as accumulation of 7-amino-4-methylcoumarin substrate	ec50	0.0005	uM
2-[4-[[5-[(2S)-2-(methoxymethyl)pyrrolidin-1-yl]sulfonyl-2,3-dioxoindol-1-yl]methyl]phenoxy]ethyl 4-methylbenzenesulfonate	271887: Binding affinity to human caspase 3	ki	0.0008	uM
(3S)-3-[[(2S)-2-[[(2S)-2-[[(2S)-2-acetamido-3-carboxypropanoyl]amino]-4-carboxybutanoyl]amino]-3-methylbutanoyl]amino]-4-oxo-7-phenylheptanoic acid	1796493: Caspase Inhibition Assay from Article 10.1021/jm0305523: “Reducing the peptidyl features of caspase-3 inhibitors: a structural analysis.”	ic50	0.0008	uM
N-(4-morpholin-4-ylphenyl)-3-oxo-1,2-benzothiazole-2-carboxamide	1125749: Inhibition of human recombinant caspase-3 using Ac-LDEVD-AMC as substrate after 10 mins by fluorescence assay	ic50	0.0011	uM
5-[(2S)-2-(methoxymethyl)pyrrolidin-1-yl]sulfonyl-1-methylindole-2,3-dione	271887: Binding affinity to human caspase 3	ki	0.0012	uM
1-[(4-iodophenyl)methyl]-5-[(2S)-2-(phenoxymethyl)pyrrolidin-1-yl]sulfonylindole-2,3-dione	271887: Binding affinity to human caspase 3	ki	0.0012	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	49512: Inhibitory activity against human Caspase-3 using Ac-AspGluValAsp as substrate	ic50	0.0012	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	0.0012	uM
8-[(2S)-2-(phenoxymethyl)pyrrolidin-1-yl]sulfonylspiro[2,4-dihydropyrimido[1,2-a]indole-3,1’-cyclobutane]-10-one	1799299: Caspase-3 Inhibition Assay from Article 10.1016/j.bmc.2009.09.036: “3,4-Dihydropyrimido(1,2-a)indol-10(2H)-ones as potent non-peptidic inhibitors of caspase-3.”	ic50	0.0013	uM
3-[2-[5-tert-butyl-3-[(4-methyl-1,2,5-oxadiazol-3-yl)methylamino]-2-oxopyrazin-1-yl]butanoylamino]-5-[methyl(pentyl)amino]-4-oxopentanoic acid;hydrochloride	238851: Inhibitory concentration against recombinant human caspase-3 in neuronal precursor (NT2) cells	ki	0.0014	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	0.0018	uM
1-[[4-[tert-butyl(dimethyl)silyl]oxyphenyl]methyl]-5-[(2S)-2-(methoxymethyl)pyrrolidin-1-yl]sulfonylindole-2,3-dione	271887: Binding affinity to human caspase 3	ki	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
8-[(2S)-2-(phenoxymethyl)pyrrolidin-1-yl]sulfonylspiro[2,4-dihydropyrimido[1,2-a]indole-3,1’-cyclopentane]-10-one	1799299: Caspase-3 Inhibition Assay from Article 10.1016/j.bmc.2009.09.036: “3,4-Dihydropyrimido(1,2-a)indol-10(2H)-ones as potent non-peptidic inhibitors of caspase-3.”	ic50	0.0023	uM
1-[(4-fluorophenyl)methyl]-5-[(2S)-2-(oxan-4-yloxymethyl)pyrrolidin-1-yl]sulfonylindole-2,3-dione	389836: Inhibition of human recombinant caspase 3 assessed as accumulation of 7-amino-4-methylcoumarin substrate	ec50	0.0023	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	49532: Inhibitory concentration of compound required against Caspase-3 compared to acylated dipeptides	ic50	0.0023	uM
3,3-dimethyl-8-[(2S)-2-(pyridin-3-yloxymethyl)pyrrolidin-1-yl]sulfonyl-2,4-dihydropyrimido[1,2-a]indol-10-one	1799299: Caspase-3 Inhibition Assay from Article 10.1016/j.bmc.2009.09.036: “3,4-Dihydropyrimido(1,2-a)indol-10(2H)-ones as potent non-peptidic inhibitors of caspase-3.”	ic50	0.0024	uM
1-methyl-5-[(2S)-2-(phenoxymethyl)pyrrolidin-1-yl]sulfonylindole-2,3-dione	375062: Inhibition of human recombinant caspase 3 assessed as accumulation of cleaved fluorogenic 7-amino-4-methylcoumarin after 10 mins	ic50	0.0024	uM
7-bromo-1-(4-hydroxybutyl)-5-[(2S)-2-(methoxymethyl)pyrrolidin-1-yl]sulfonylindole-2,3-dione	1170192: Inhibition of human recombinant caspase 3 using Ac-DEVD-AMC substrate assessed as accumulation of cleaved fluorogenic product	ic50	0.0026	uM
1-butyl-7-fluoro-5-[(2S)-2-(methoxymethyl)pyrrolidin-1-yl]sulfonylindole-2,3-dione	1170192: Inhibition of human recombinant caspase 3 using Ac-DEVD-AMC substrate assessed as accumulation of cleaved fluorogenic product	ic50	0.0029	uM
(3S)-3-[[(2S,11S)-11-[[(2S)-2-acetamido-4-methoxy-4-oxobutanoyl]amino]-12-oxo-1-azatricyclo[6.4.1.04,13]trideca-4,6,8(13)-triene-2-carbonyl]amino]-5-benzylsulfanyl-4-oxopentanoic acid	49529: Inhibitory concentration of compound against caspase-3	ic50	0.0030	uM
(3S)-3-[[(2S,11S)-11-[[(2S)-2-acetamido-3-carboxypropanoyl]amino]-12-oxo-1-azatricyclo[6.4.1.04,13]trideca-4,6,8(13)-triene-2-carbonyl]amino]-5-benzylsulfanyl-4-oxopentanoic acid	1796493: Caspase Inhibition Assay from Article 10.1021/jm0305523: “Reducing the peptidyl features of caspase-3 inhibitors: a structural analysis.”	ic50	0.0030	uM
1-ethyl-3-(4-methoxyphenyl)-6-methylpyrimido[5,4-e][1,2,4]triazine-5,7-dione	683882: Inhibition of caspase3	ic50	0.0030	uM
tert-butyl 2-[2,3-dioxo-5-[(2S)-2-(phenoxymethyl)pyrrolidin-1-yl]sulfonylindol-1-yl]acetate	431515: Inhibition of caspase 3 in human SK-N-SH cells assessed as accumulation of fluorogenic 7-amino-4-methyl coumarin by fluorometric assay	ic50	0.0030	uM
1-[[4-(2-fluoroethoxy)phenyl]methyl]-5-[(2S)-2-(pyridin-3-yloxymethyl)pyrrolidin-1-yl]sulfonylindole-2,3-dione	591187: Inhibition of human caspase 3 by fluorometric assay	ic50	0.0031	uM
(3S)-3-acetamido-4-[[(2S)-3-carboxy-1-[[(2S)-1-[[(2S)-1-carboxy-3-oxopropan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]amino]-1-oxopropan-2-yl]amino]-4-oxobutanoic acid	281982: Inhibition of human caspase 3 expressed in Escherichia coli	ki	0.0032	uM
8-[(2S)-2-(methoxymethyl)pyrrolidin-1-yl]sulfonylspiro[2,4-dihydropyrimido[1,2-a]indole-3,1’-cyclobutane]-10-one	1799299: Caspase-3 Inhibition Assay from Article 10.1016/j.bmc.2009.09.036: “3,4-Dihydropyrimido(1,2-a)indol-10(2H)-ones as potent non-peptidic inhibitors of caspase-3.”	ic50	0.0033	uM
1-[(4-methoxyphenyl)methyl]-5-[(2S)-2-(pyridin-3-yloxymethyl)azetidin-1-yl]sulfonylindole-2,3-dione	591187: Inhibition of human caspase 3 by fluorometric assay	ic50	0.0033	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	49532: Inhibitory concentration of compound required against Caspase-3 compared to acylated dipeptides	ic50	0.0035	uM
1-[(4-bromophenyl)methyl]-5-[(2S)-2-(pyridin-3-yloxymethyl)pyrrolidin-1-yl]sulfonylindole-2,3-dione	292076: Inhibition of human recombinant caspase 3	ic50	0.0036	uM
1-(4-fluoro-3-hydroxybutyl)-5-[(2S)-2-(methoxymethyl)pyrrolidin-1-yl]sulfonylindole-2,3-dione	375062: Inhibition of human recombinant caspase 3 assessed as accumulation of cleaved fluorogenic 7-amino-4-methylcoumarin after 10 mins	ic50	0.0036	uM
1-[[4-(2-fluoroethoxy)phenyl]methyl]-5-[(2S)-2-(pyridin-3-yloxymethyl)azetidin-1-yl]sulfonylindole-2,3-dione	591187: Inhibition of human caspase 3 by fluorometric assay	ic50	0.0036	uM
(4S)-5-[[1-[[(3S)-2-hydroxy-5-oxooxolan-3-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-4-naphthalen-1-yloxy-5-oxopentanoic acid	49531: Inhibition of Caspase-3	ic50	0.0038	uM
1-[(4-methoxyphenyl)methyl]-5-[(2S)-2-(pyridin-3-yloxymethyl)pyrrolidin-1-yl]sulfonylindole-2,3-dione	256994: Inhibitory activity against caspase 3 using Ac-DEVD-AMC substrate	ic50	0.0039	uM
1-[(4-hydroxyphenyl)methyl]-5-[(2S)-2-(pyridin-3-yloxymethyl)pyrrolidin-1-yl]sulfonylindole-2,3-dione	292076: Inhibition of human recombinant caspase 3	ic50	0.0039	uM
4-methyl-8-morpholin-4-ylsulfonyl-2-(1,3,5-trimethylpyrazol-4-yl)pyrrolo[3,4-c]quinoline-1,3-dione	1796448: Caspase Inhibition Assay from Article 10.1016/j.bmcl.2005.02.027: “1,3-Dioxo-4-methyl-2,3-dihydro-1H-pyrrolo[3,4-c]quinolines as potent caspase-3 inhibitors.”	ic50	0.0040	uM
1-[(4-hydroxyphenyl)methyl]-5-[(2S)-2-(phenoxymethyl)pyrrolidin-1-yl]sulfonylindole-2,3-dione	271887: Binding affinity to human caspase 3	ki	0.0040	uM
5-[(2S)-2-(phenoxymethyl)pyrrolidin-1-yl]sulfonyl-1-(pyridin-4-ylmethyl)indole-2,3-dione	1796419: Caspase Inhibition Assay from Article 10.1021/jm0100537: “Potent and selective nonpeptide inhibitors of caspases 3 and 7.”	ic50	0.0042	uM
1-[(4-methylsulfanylphenyl)methyl]-5-[(2S)-2-(pyridin-3-yloxymethyl)pyrrolidin-1-yl]sulfonylindole-2,3-dione	1796431: Caspase Inhibition Assay from Article 10.1021/jm0506625: “N-benzylisatin sulfonamide analogues as potent caspase-3 inhibitors: synthesis, in vitro activity, and molecular modeling studies.”	ic50	0.0044	uM
8-[(2S)-2-[(5-chloro-3-pyridinyl)oxymethyl]pyrrolidin-1-yl]sulfonyl-3,3-dimethyl-2,4-dihydropyrimido[1,2-a]indol-10-one	1799299: Caspase-3 Inhibition Assay from Article 10.1016/j.bmc.2009.09.036: “3,4-Dihydropyrimido(1,2-a)indol-10(2H)-ones as potent non-peptidic inhibitors of caspase-3.”	ic50	0.0044	uM
1-[[1-(2-fluoroethyl)triazol-4-yl]methyl]-5-[(2S)-2-(pyridin-3-yloxymethyl)pyrrolidin-1-yl]sulfonylindole-2,3-dione	591187: Inhibition of human caspase 3 by fluorometric assay	ic50	0.0045	uM
5-[(2S)-2-(phenoxymethyl)pyrrolidin-1-yl]sulfonyl-1-prop-2-enylindole-2,3-dione	1796419: Caspase Inhibition Assay from Article 10.1021/jm0100537: “Potent and selective nonpeptide inhibitors of caspases 3 and 7.”	ic50	0.0046	uM
7-chloro-1-(3-fluoropropyl)-5-[(2S)-2-(methoxymethyl)pyrrolidin-1-yl]sulfonylindole-2,3-dione	1170192: Inhibition of human recombinant caspase 3 using Ac-DEVD-AMC substrate assessed as accumulation of cleaved fluorogenic product	ic50	0.0048	uM
1-butyl-5-[(2S)-2-(2-fluoroethoxymethyl)pyrrolidin-1-yl]sulfonylindole-2,3-dione	740441: Inhibition of human recombinant caspase 3 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	0.0048	uM
1-[(4-methoxyphenyl)methyl]-5-[(2S)-2-(phenoxymethyl)pyrrolidin-1-yl]sulfonylindole-2,3-dione	271887: Binding affinity to human caspase 3	ki	0.0048	uM

CTD chemical–gene interactions

2080 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Arsenic Trioxide	affects cotreatment, increases expression, decreases expression, decreases response to substance, increases cleavage (+12 more)	162
Cisplatin	decreases activity, affects response to substance, increases activity, increases reaction, affects cotreatment (+9 more)	124
Acetylcysteine	increases activity, increases cleavage, decreases expression, increases expression, increases abundance (+7 more)	123
Resveratrol	increases abundance, decreases activity, decreases cleavage, increases reaction, decreases reaction (+12 more)	105
Doxorubicin	affects cleavage, increases cleavage, increases localization, increases expression, affects cotreatment (+14 more)	97
Quercetin	decreases reaction, increases cleavage, affects cotreatment, affects reaction, increases activity (+7 more)	91
Hydrogen Peroxide	increases reaction, affects cotreatment, decreases reaction, increases expression, decreases abundance (+7 more)	61
Bortezomib	increases response to substance, increases phosphorylation, affects reaction, decreases reaction, increases activity (+6 more)	58
1-Methyl-4-phenylpyridinium	decreases reaction, affects expression, affects cleavage, affects reaction, decreases expression (+5 more)	47
sodium arsenite	decreases reaction, increases cleavage, decreases cleavage, affects reaction, affects response to substance (+11 more)	46
Fluorouracil	increases cleavage, increases expression, decreases expression, decreases response to substance, decreases cleavage (+7 more)	46
pyrazolanthrone	increases expression, decreases reaction, increases cleavage, increases activity, affects cotreatment (+3 more)	44
Paclitaxel	decreases expression, affects cotreatment, decreases reaction, increases cleavage, increases expression (+3 more)	42
Paraquat	affects cotreatment, increases reaction, increases cleavage, increases abundance, decreases expression (+5 more)	35
Plant Extracts	decreases reaction, increases expression, increases activity, decreases expression, increases abundance (+2 more)	35
Curcumin	decreases reaction, affects reaction, increases expression, decreases expression, increases activity (+5 more)	34
Staurosporine	increases reaction, decreases reaction, increases expression, increases cleavage, decreases expression (+2 more)	33
3-methyladenine	increases expression, increases reaction, increases degradation, increases activity, increases cleavage (+5 more)	32
Tretinoin	decreases reaction, increases activity, increases cleavage, affects cotreatment, affects cleavage (+3 more)	32
Etoposide	decreases reaction, increases cleavage, increases activity, affects reaction, increases reaction (+6 more)	31
SB 203580	increases reaction, decreases reaction, affects cotreatment, increases cleavage, increases expression (+3 more)	30
benzoylcarbonyl-aspartyl-glutamyl-valyl-aspartyl-fluoromethyl ketone	increases cleavage, decreases expression, increases expression, decreases activity, decreases reaction (+3 more)	30
Vorinostat	affects cotreatment, decreases activity, increases abundance, decreases reaction, increases activity (+3 more)	30
benzyloxycarbonyl-valyl-alanyl-aspartic acid	increases cleavage, increases expression, affects cotreatment, increases reaction, increases response to substance (+3 more)	29
Cadmium Chloride	increases activity, affects cotreatment, decreases activity, increases reaction, affects reaction (+6 more)	28
Rotenone	decreases reaction, increases activity, affects cotreatment, decreases activity, increases reaction (+4 more)	27
2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one	decreases reaction, increases expression, increases reaction, affects reaction, increases abundance (+6 more)	24
Cadmium	decreases reaction, increases cleavage, increases abundance, increases degradation, increases reaction (+7 more)	24
Particulate Matter	decreases reaction, decreases expression, affects cleavage, increases secretion, increases cleavage (+5 more)	22
bisphenol A	affects cotreatment, decreases activity, decreases expression, increases expression, increases activity (+3 more)	21

ChEMBL screening assays

349 unique, capped per target: 327 binding, 16 functional, 4 toxicity, 2 admet

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1004121	Binding	Inhibition of human recombinant caspase 3 assessed as accumulation of cleaved fluorogenic 7-amino-4-methylcoumarin after 10 mins	Fluorinated isatin derivatives. Part 2. New N-substituted 5-pyrrolidinylsulfonyl isatins as potential tools for molecular imaging of caspases in apoptosis. — *J Med Chem*
CHEMBL1738414	Functional	PUBCHEM_BIOASSAY: Dose Response confirmation of inhibitors of Sentrin-specific proteases (SENPs) using a Caspase-3 Selectivity assay. (Class of assay: confirmatory) [Related pubchem assays (depositor defined):AID2540, AID2599, AID434973, AI	PubChem BioAssay data set
CHEMBL3603478	ADMET	Prodrug conversion assessed as recombinant human caspase-3-mediated 6-(3-(2-aminoethylthio)-2,5-dioxopyrrolidin-1-yl)-N-((2S,3S,4S,6R)-3-hydroxy-2-methyl-6-((1S,3S)-3,5,12-trihydroxy-3-(2-hydroxyacetyl)-10-methoxy-6,11-dioxo-1,2,3,4,6,11-he	Optimization of a Stable Linker Involved DEVD Peptide-Doxorubicin Conjugate That Is Activated upon Radiation-Induced Caspase-3-Mediated Apoptosis. — *J Med Chem*

Cellosaurus cell lines

12 cell lines: 11 cancer cell line, 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B1M4	Abcam HeLa CASP3 KO	Cancer cell line	Female
CVCL_B7WE	Abcam Raji CASP3 KO	Cancer cell line	Male
CVCL_B9WX	Abcam THP-1 CASP3 KO	Cancer cell line	Male
CVCL_C6YY	Abcam PC-3 CASP3 KO	Cancer cell line	Male
CVCL_D6AG	HyCyte A-549 KO-hCASP3	Cancer cell line	Male
CVCL_D7LS	Ubigene A-549 CASP3 KO	Cancer cell line	Male
CVCL_D8IH	Ubigene HCT 116 CASP3 KO	Cancer cell line	Male
CVCL_D9B2	Ubigene HEK293 CASP3 KO	Transformed cell line	Female
CVCL_D9ZE	Ubigene HeLa CASP3 KO	Cancer cell line	Female
CVCL_F5AA	EDITGENE CASP3 Knockout A549 Cell Line	Cancer cell line	Male

Clinical trials (associated diseases)

Via MONDO — disease-level, not drug-specific.

Predicted chemistry — Sugi Predict

The predicted patent-compound landscape for CASP3 across ~30M SureChEMBL compounds — explore on Sugi Predict.