Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTIJRBE7)

DOT Name Caspase-3 (CASP3)
Synonyms CASP-3; EC 3.4.22.56; Apopain; Cysteine protease CPP32; CPP-32; Protein Yama; SREBP cleavage activity 1; SCA-1
Gene Name CASP3
UniProt ID
CASP3_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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PDB ID
1CP3 ; 1GFW ; 1I3O ; 1NME ; 1NMQ ; 1NMS ; 1PAU ; 1QX3 ; 1RE1 ; 1RHJ ; 1RHK ; 1RHM ; 1RHQ ; 1RHR ; 1RHU ; 2C1E ; 2C2K ; 2C2M ; 2C2O ; 2CDR ; 2CJX ; 2CJY ; 2CNK ; 2CNL ; 2CNN ; 2CNO ; 2DKO ; 2H5I ; 2H5J ; 2H65 ; 2J30 ; 2J31 ; 2J32 ; 2J33 ; 2XYG ; 2XYH ; 2XYP ; 2XZD ; 2XZT ; 2Y0B ; 3DEH ; 3DEI ; 3DEJ ; 3DEK ; 3EDQ ; 3GJQ ; 3GJR ; 3GJS ; 3GJT ; 3H0E ; 3ITN ; 3KJF ; 3PCX ; 3PD0 ; 3PD1 ; 4DCJ ; 4DCO ; 4DCP ; 4EHA ; 4EHD ; 4EHF ; 4EHH ; 4EHK ; 4EHL ; 4EHN ; 4JJE ; 4JQY ; 4JQZ ; 4JR0 ; 4PRY ; 4PS0 ; 4QTX ; 4QTY ; 4QU0 ; 4QU5 ; 4QU8 ; 4QU9 ; 4QUA ; 4QUB ; 4QUD ; 4QUE ; 4QUG ; 4QUH ; 4QUI ; 4QUJ ; 4QUL ; 5I9B ; 5I9T ; 5IAB ; 5IAE ; 5IAG ; 5IAJ ; 5IAK ; 5IAN ; 5IAR ; 5IAS ; 5IBC ; 5IBP ; 5IBR ; 5IC4 ; 7XN4 ; 7XN5 ; 7XN6
EC Number
3.4.22.56
Pfam ID
PF00656
Sequence
MENTENSVDSKSIKNLEPKIIHGSESMDSGISLDNSYKMDYPEMGLCIIINNKNFHKSTG
MTSRSGTDVDAANLRETFRNLKYEVRNKNDLTREEIVELMRDVSKEDHSKRSSFVCVLLS
HGEEGIIFGTNGPVDLKKITNFFRGDRCRSLTGKPKLFIIQACRGTELDCGIETDSGVDD
DMACHKIPVEADFLYAYSTAPGYYSWRNSKDGSWFIQSLCAMLKQYADKLEFMHILTRVN
RKVATEFESFSFDATFHAKKQIPCIVSMLTKELYFYH
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. 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.
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.
KEGG Pathway
Platinum drug resistance (hsa01524 )
MAPK sig.ling pathway (hsa04010 )
p53 sig.ling pathway (hsa04115 )
Efferocytosis (hsa04148 )
Apoptosis (hsa04210 )
Apoptosis - multiple species (hsa04215 )
Cytosolic D.-sensing pathway (hsa04623 )
.tural killer cell mediated cytotoxicity (hsa04650 )
IL-17 sig.ling pathway (hsa04657 )
TNF sig.ling pathway (hsa04668 )
Serotonergic sy.pse (hsa04726 )
Non-alcoholic fatty liver disease (hsa04932 )
AGE-RAGE sig.ling pathway in diabetic complications (hsa04933 )
Alcoholic liver disease (hsa04936 )
Alzheimer disease (hsa05010 )
Parkinson disease (hsa05012 )
Amyotrophic lateral sclerosis (hsa05014 )
Huntington disease (hsa05016 )
Prion disease (hsa05020 )
Pathways of neurodegeneration - multiple diseases (hsa05022 )
Epithelial cell sig.ling in Helicobacter pylori infection (hsa05120 )
Pathogenic Escherichia coli infection (hsa05130 )
Salmonella infection (hsa05132 )
Pertussis (hsa05133 )
Legionellosis (hsa05134 )
Toxoplasmosis (hsa05145 )
Amoebiasis (hsa05146 )
Tuberculosis (hsa05152 )
Hepatitis C (hsa05160 )
Hepatitis B (hsa05161 )
Measles (hsa05162 )
Human cytomegalovirus infection (hsa05163 )
Influenza A (hsa05164 )
Human papillomavirus infection (hsa05165 )
Kaposi sarcoma-associated herpesvirus infection (hsa05167 )
Herpes simplex virus 1 infection (hsa05168 )
Epstein-Barr virus infection (hsa05169 )
Human immunodeficiency virus 1 infection (hsa05170 )
Pathways in cancer (hsa05200 )
Viral carcinogenesis (hsa05203 )
Proteoglycans in cancer (hsa05205 )
MicroR.s in cancer (hsa05206 )
Colorectal cancer (hsa05210 )
Small cell lung cancer (hsa05222 )
Viral myocarditis (hsa05416 )
Lipid and atherosclerosis (hsa05417 )
Reactome Pathway
SMAC (DIABLO) binds to IAPs (R-HSA-111463 )
SMAC(DIABLO)-mediated dissociation of IAP (R-HSA-111464 )
Apoptotic cleavage of cellular proteins (R-HSA-111465 )
SMAC, XIAP-regulated apoptotic response (R-HSA-111469 )
Apoptosis induced DNA fragmentation (R-HSA-140342 )
Degradation of the extracellular matrix (R-HSA-1474228 )
Signaling by Hippo (R-HSA-2028269 )
NADE modulates death signalling (R-HSA-205025 )
Stimulation of the cell death response by PAK-2p34 (R-HSA-211736 )
Caspase-mediated cleavage of cytoskeletal proteins (R-HSA-264870 )
Apoptotic cleavage of cell adhesion proteins (R-HSA-351906 )
Caspase activation via Dependence Receptors in the absence of ligand (R-HSA-418889 )
Other interleukin signaling (R-HSA-449836 )
Pyroptosis (R-HSA-5620971 )
Activation of caspases through apoptosome-mediated cleavage (R-HSA-111459 )
BioCyc Pathway
MetaCyc:HS09058-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
This DOT Affected the Drug Response of 1 Drug(s)
Drug Name Drug ID Highest Status Interaction REF
Digoxin DMQCTIH Approved Caspase-3 (CASP3) increases the Mitochondrial toxicity ADR of Digoxin. [93]
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1 Drug(s) Affected the Post-Translational Modifications of This DOT
Drug Name Drug ID Highest Status Interaction REF
Valproate DMCFE9I Approved Valproate decreases the methylation of Caspase-3 (CASP3). [1]
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91 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Ciclosporin DMAZJFX Approved Ciclosporin increases the activity of Caspase-3 (CASP3). [2]
Tretinoin DM49DUI Approved Tretinoin increases the activity of Caspase-3 (CASP3). [3]
Acetaminophen DMUIE76 Approved Acetaminophen decreases the activity of Caspase-3 (CASP3). [4]
Doxorubicin DMVP5YE Approved Doxorubicin increases the expression of Caspase-3 (CASP3). [5]
Cupric Sulfate DMP0NFQ Approved Cupric Sulfate increases the expression of Caspase-3 (CASP3). [6]
Cisplatin DMRHGI9 Approved Cisplatin increases the expression of Caspase-3 (CASP3). [7]
Estradiol DMUNTE3 Approved Estradiol increases the expression of Caspase-3 (CASP3). [8]
Ivermectin DMDBX5F Approved Ivermectin decreases the expression of Caspase-3 (CASP3). [9]
Arsenic DMTL2Y1 Approved Arsenic increases the expression of Caspase-3 (CASP3). [10]
Quercetin DM3NC4M Approved Quercetin increases the expression of Caspase-3 (CASP3). [11]
Temozolomide DMKECZD Approved Temozolomide increases the activity of Caspase-3 (CASP3). [12]
Arsenic trioxide DM61TA4 Approved Arsenic trioxide decreases the expression of Caspase-3 (CASP3). [13]
Hydrogen peroxide DM1NG5W Approved Hydrogen peroxide increases the expression of Caspase-3 (CASP3). [14]
Calcitriol DM8ZVJ7 Approved Calcitriol increases the activity of Caspase-3 (CASP3). [15]
Vorinostat DMWMPD4 Approved Vorinostat increases the activity of Caspase-3 (CASP3). [16]
Testosterone DM7HUNW Approved Testosterone decreases the expression of Caspase-3 (CASP3). [17]
Triclosan DMZUR4N Approved Triclosan decreases the expression of Caspase-3 (CASP3). [18]
Carbamazepine DMZOLBI Approved Carbamazepine affects the expression of Caspase-3 (CASP3). [19]
Methotrexate DM2TEOL Approved Methotrexate increases the expression of Caspase-3 (CASP3). [20]
Marinol DM70IK5 Approved Marinol increases the activity of Caspase-3 (CASP3). [21]
Zoledronate DMIXC7G Approved Zoledronate increases the expression of Caspase-3 (CASP3). [22]
Phenobarbital DMXZOCG Approved Phenobarbital affects the expression of Caspase-3 (CASP3). [23]
Progesterone DMUY35B Approved Progesterone increases the activity of Caspase-3 (CASP3). [15]
Fluorouracil DMUM7HZ Approved Fluorouracil increases the expression of Caspase-3 (CASP3). [24]
Dexamethasone DMMWZET Approved Dexamethasone decreases the activity of Caspase-3 (CASP3). [25]
Demecolcine DMCZQGK Approved Demecolcine increases the activity of Caspase-3 (CASP3). [27]
Niclosamide DMJAGXQ Approved Niclosamide decreases the expression of Caspase-3 (CASP3). [28]
Cannabidiol DM0659E Approved Cannabidiol increases the expression of Caspase-3 (CASP3). [29]
Bortezomib DMNO38U Approved Bortezomib increases the activity of Caspase-3 (CASP3). [31]
Troglitazone DM3VFPD Approved Troglitazone increases the activity of Caspase-3 (CASP3). [32]
Hydroquinone DM6AVR4 Approved Hydroquinone decreases the expression of Caspase-3 (CASP3). [33]
Diethylstilbestrol DMN3UXQ Approved Diethylstilbestrol increases the activity of Caspase-3 (CASP3). [34]
Rosiglitazone DMILWZR Approved Rosiglitazone decreases the expression of Caspase-3 (CASP3). [35]
Ethanol DMDRQZU Approved Ethanol increases the expression of Caspase-3 (CASP3). [36]
Cytarabine DMZD5QR Approved Cytarabine increases the activity of Caspase-3 (CASP3). [37]
Aspirin DM672AH Approved Aspirin increases the activity of Caspase-3 (CASP3). [38]
Etoposide DMNH3PG Approved Etoposide increases the activity of Caspase-3 (CASP3). [39]
Irinotecan DMP6SC2 Approved Irinotecan increases the activity of Caspase-3 (CASP3). [40]
Paclitaxel DMLB81S Approved Paclitaxel increases the expression of Caspase-3 (CASP3). [41]
Diclofenac DMPIHLS Approved Diclofenac increases the activity of Caspase-3 (CASP3). [42]
Nicotine DMWX5CO Approved Nicotine increases the expression of Caspase-3 (CASP3). [43]
Dasatinib DMJV2EK Approved Dasatinib increases the activity of Caspase-3 (CASP3). [44]
Clozapine DMFC71L Approved Clozapine increases the activity of Caspase-3 (CASP3). [2]
Indomethacin DMSC4A7 Approved Indomethacin increases the expression of Caspase-3 (CASP3). [47]
Menthol DMG2KW7 Approved Menthol increases the expression of Caspase-3 (CASP3). [48]
Mitomycin DMH0ZJE Approved Mitomycin increases the activity of Caspase-3 (CASP3). [49]
Azacitidine DMTA5OE Approved Azacitidine affects the expression of Caspase-3 (CASP3). [50]
Cidofovir DMA13GD Approved Cidofovir decreases the activity of Caspase-3 (CASP3). [51]
Cocaine DMSOX7I Approved Cocaine increases the expression of Caspase-3 (CASP3). [52]
Simvastatin DM30SGU Approved Simvastatin increases the expression of Caspase-3 (CASP3). [53]
Topotecan DMP6G8T Approved Topotecan increases the activity of Caspase-3 (CASP3). [54]
Gemcitabine DMSE3I7 Approved Gemcitabine increases the activity of Caspase-3 (CASP3). [55]
Melphalan DMOLNHF Approved Melphalan increases the activity of Caspase-3 (CASP3). [56]
Fenofibrate DMFKXDY Approved Fenofibrate decreases the expression of Caspase-3 (CASP3). [57]
Mitoxantrone DMM39BF Approved Mitoxantrone increases the activity of Caspase-3 (CASP3). [58]
Cyclophosphamide DM4O2Z7 Approved Cyclophosphamide increases the expression of Caspase-3 (CASP3). [24]
Mifepristone DMGZQEF Approved Mifepristone decreases the expression of Caspase-3 (CASP3). [59]
Zidovudine DM4KI7O Approved Zidovudine increases the expression of Caspase-3 (CASP3). [60]
Clodronate DM9Y6X7 Approved Clodronate increases the expression of Caspase-3 (CASP3). [61]
Sulindac DM2QHZU Approved Sulindac increases the activity of Caspase-3 (CASP3). [62]
Capsaicin DMGMF6V Approved Capsaicin increases the activity of Caspase-3 (CASP3). [63]
Alitretinoin DMME8LH Approved Alitretinoin increases the expression of Caspase-3 (CASP3). [64]
Daunorubicin DMQUSBT Approved Daunorubicin increases the activity of Caspase-3 (CASP3). [66]
Acocantherin DM7JT24 Approved Acocantherin increases the activity of Caspase-3 (CASP3). [68]
Acetic Acid, Glacial DM4SJ5Y Approved Acetic Acid, Glacial decreases the expression of Caspase-3 (CASP3). [69]
Thalidomide DM70BU5 Approved Thalidomide decreases the activity of Caspase-3 (CASP3). [70]
Motexafin gadolinium DMEJKRF Approved Motexafin gadolinium decreases the expression of Caspase-3 (CASP3). [69]
Liothyronine DM6IR3P Approved Liothyronine decreases the expression of Caspase-3 (CASP3). [71]
Colchicine DM2POTE Approved Colchicine increases the activity of Caspase-3 (CASP3). [72]
Hydroxyurea DMOQVU9 Approved Hydroxyurea increases the activity of Caspase-3 (CASP3). [73]
Vitamin C DMXJ7O8 Approved Vitamin C increases the expression of Caspase-3 (CASP3). [74]
Enzalutamide DMGL19D Approved Enzalutamide decreases the expression of Caspase-3 (CASP3). [75]
Sorafenib DMS8IFC Approved Sorafenib decreases the expression of Caspase-3 (CASP3). [76]
Fluoxetine DM3PD2C Approved Fluoxetine increases the activity of Caspase-3 (CASP3). [2]
Beta-carotene DM0RXBT Approved Beta-carotene increases the activity of Caspase-3 (CASP3). [77]
Imatinib DM7RJXL Approved Imatinib increases the activity of Caspase-3 (CASP3). [78]
Sertraline DM0FB1J Approved Sertraline increases the activity of Caspase-3 (CASP3). [79]
Ritonavir DMU764S Approved Ritonavir decreases the activity of Caspase-3 (CASP3). [80]
Nefazodone DM4ZS8M Approved Nefazodone increases the activity of Caspase-3 (CASP3). [2]
Dihydroartemisinin DMBXVMZ Approved Dihydroartemisinin increases the expression of Caspase-3 (CASP3). [81]
Estrone DM5T6US Approved Estrone increases the activity of Caspase-3 (CASP3). [2]
Dinoprostone DMTYOPD Approved Dinoprostone decreases the activity of Caspase-3 (CASP3). [82]
Dactinomycin DM2YGNW Approved Dactinomycin decreases the expression of Caspase-3 (CASP3). [83]
Chenodiol DMQ8JIK Approved Chenodiol increases the activity of Caspase-3 (CASP3). [84]
Docetaxel DMDI269 Approved Docetaxel increases the activity of Caspase-3 (CASP3). [85]
Cholecalciferol DMGU74E Approved Cholecalciferol increases the activity of Caspase-3 (CASP3). [86]
Dopamine DMPGUCF Approved Dopamine increases the activity of Caspase-3 (CASP3). [87]
Nitric Oxide DM1RBYG Approved Nitric Oxide decreases the activity of Caspase-3 (CASP3). [88]
Ardeparin DMYRX8B Approved Ardeparin decreases the activity of Caspase-3 (CASP3). [90]
Adenosine triphosphate DM79F6G Approved Adenosine triphosphate increases the expression of Caspase-3 (CASP3). [61]
Melatonin DMKWFBT Approved Melatonin increases the activity of Caspase-3 (CASP3). [92]
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⏷ Show the Full List of 91 Drug(s)
8 Drug(s) Affected the Protein Interaction/Cellular Processes of This DOT
Drug Name Drug ID Highest Status Interaction REF
Folic acid DMEMBJC Approved Folic acid increases the cleavage of Caspase-3 (CASP3). [26]
Isotretinoin DM4QTBN Approved Isotretinoin increases the cleavage of Caspase-3 (CASP3). [30]
DTI-015 DMXZRW0 Approved DTI-015 increases the cleavage of Caspase-3 (CASP3). [45]
Malathion DMXZ84M Approved Malathion increases the cleavage of Caspase-3 (CASP3). [46]
Methamphetamine DMPM4SK Approved Methamphetamine decreases the cleavage of Caspase-3 (CASP3). [65]
Palbociclib DMD7L94 Approved Palbociclib decreases the cleavage of Caspase-3 (CASP3). [67]
Lovastatin DM9OZWQ Approved Lovastatin increases the cleavage of Caspase-3 (CASP3). [89]
Propofol DMB4OLE Approved Propofol increases the cleavage of Caspase-3 (CASP3). [91]
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⏷ Show the Full List of 8 Drug(s)

References

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