Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTD4RFFG)

• DOT Name: Caspase-9 (CASP9)
• Synonyms: CASP-9; EC 3.4.22.62; Apoptotic protease Mch-6; Apoptotic protease-activating factor 3; APAF-3; ICE-like apoptotic protease 6; ICE-LAP6
• Gene Name: CASP9
• UniProt ID: CASP9_HUMAN
• PDB ID: 1JXQ; 1NW9; 2AR9; 3D9T; 3V3K; 3YGS; 4RHW; 5JUY; 5WVC; 5WVE
• EC Number: 3.4.22.62
• Pfam ID: PF00619 ; PF00656
• Sequence:
  MDEADRRLLRRCRLRLVEELQVDQLWDALLSRELFRPHMIEDIQRAGSGSRRDQARQLII
  DLETRGSQALPLFISCLEDTGQDMLASFLRTNRQAAKLSKPTLENLTPVVLRPEIRKPEV
  LRPETPRPVDIGSGGFGDVGALESLRGNADLAYILSMEPCGHCLIINNVNFCRESGLRTR
  TGSNIDCEKLRRRFSSLHFMVEVKGDLTAKKMVLALLELAQQDHGALDCCVVVILSHGCQ
  ASHLQFPGAVYGTDGCPVSVEKIVNIFNGTSCPSLGGKPKLFFIQACGGEQKDHGFEVAS
  TSPEDESPGSNPEPDATPFQEGLRTFDQLDAISSLPTPSDIFVSYSTFPGFVSWRDPKSG
  SWYVETLDDIFEQWAHSEDLQSLLLRVANAVSVKGIYKQMPGCFNFLRKKLFFKTS
• Function: Involved in the activation cascade of caspases responsible for apoptosis execution. Binding of caspase-9 to Apaf-1 leads to activation of the protease which then cleaves and activates effector caspases caspase-3 (CASP3) or caspase-7 (CASP7). Promotes DNA damage-induced apoptosis in a ABL1/c-Abl-dependent manner. Proteolytically cleaves poly(ADP-ribose) polymerase (PARP); [Isoform 2]: Lacks activity is an dominant-negative inhibitor of caspase-9.
• Tissue Specificity: Ubiquitous, with highest expression in the heart, moderate expression in liver, skeletal muscle, and pancreas. Low levels in all other tissues. Within the heart, specifically expressed in myocytes.
• KEGG Pathway:
  Platinum drug resistance (hsa01524)
  p53 sig.ling pathway (hsa04115)
  PI3K-Akt sig.ling pathway (hsa04151)
  Apoptosis (hsa04210)
  Apoptosis - multiple species (hsa04215)
  VEGF sig.ling pathway (hsa04370)
  Thyroid hormone sig.ling pathway (hsa04919)
  Alzheimer disease (hsa05010)
  Parkinson disease (hsa05012)
  Amyotrophic lateral sclerosis (hsa05014)
  Huntington disease (hsa05016)
  Prion disease (hsa05020)
  Pathways of neurodegeneration - multiple diseases (hsa05022)
  Pathogenic Escherichia coli infection (hsa05130)
  Legionellosis (hsa05134)
  Toxoplasmosis (hsa05145)
  Tuberculosis (hsa05152)
  Hepatitis C (hsa05160)
  Hepatitis B (hsa05161)
  Measles (hsa05162)
  Human cytomegalovirus infection (hsa05163)
  Influenza A (hsa05164)
  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)
  Colorectal cancer (hsa05210)
  Pancreatic cancer (hsa05212)
  Endometrial cancer (hsa05213)
  Prostate cancer (hsa05215)
  Small cell lung cancer (hsa05222)
  Non-small cell lung cancer (hsa05223)
  Viral myocarditis (hsa05416)
  Lipid and atherosclerosis (hsa05417)
• Reactome Pathway:
  Activation of caspases through apoptosome-mediated cleavage (R-HSA-111459)
  SMAC (DIABLO) binds to IAPs (R-HSA-111463)
  SMAC(DIABLO)-mediated dissociation of IAP (R-HSA-111464)
  NOD1/2 Signaling Pathway (R-HSA-168638)
  AKT phosphorylates targets in the cytosol (R-HSA-198323)
  Caspase activation via Dependence Receptors in the absence of ligand (R-HSA-418889)
  Constitutive Signaling by AKT1 E17K in Cancer (R-HSA-5674400)
  Regulation of the apoptosome activity (R-HSA-9627069)
  Formation of apoptosome (R-HSA-111458)
• BioCyc Pathway: MetaCyc:HS05705-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

This DOT Affected the Drug Response of 2 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Bortezomib	DMNO38U	Approved	Caspase-9 (CASP9) increases the response to substance of Bortezomib.	[94]
Rhucin	DM3ADGP	Approved	Caspase-9 (CASP9) affects the response to substance of Rhucin.	[95]

1 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of Caspase-9 (CASP9).	[1]

81 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Caspase-9 (CASP9).	[2]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the activity of Caspase-9 (CASP9).	[3]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Caspase-9 (CASP9).	[4]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Caspase-9 (CASP9).	[4]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Caspase-9 (CASP9).	[5]
Arsenic	DMTL2Y1	Approved	Arsenic increases the expression of Caspase-9 (CASP9).	[6]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Caspase-9 (CASP9).	[7]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Caspase-9 (CASP9).	[9]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide increases the expression of Caspase-9 (CASP9).	[10]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Caspase-9 (CASP9).	[11]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the activity of Caspase-9 (CASP9).	[12]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Caspase-9 (CASP9).	[13]
Triclosan	DMZUR4N	Approved	Triclosan increases the expression of Caspase-9 (CASP9).	[14]
Methotrexate	DM2TEOL	Approved	Methotrexate decreases the expression of Caspase-9 (CASP9).	[15]
Marinol	DM70IK5	Approved	Marinol increases the activity of Caspase-9 (CASP9).	[17]
Zoledronate	DMIXC7G	Approved	Zoledronate increases the activity of Caspase-9 (CASP9).	[18]
Fluorouracil	DMUM7HZ	Approved	Fluorouracil decreases the expression of Caspase-9 (CASP9).	[20]
Dexamethasone	DMMWZET	Approved	Dexamethasone increases the activity of Caspase-9 (CASP9).	[21]
Niclosamide	DMJAGXQ	Approved	Niclosamide increases the expression of Caspase-9 (CASP9).	[22]
Cannabidiol	DM0659E	Approved	Cannabidiol increases the expression of Caspase-9 (CASP9).	[23]
Troglitazone	DM3VFPD	Approved	Troglitazone increases the activity of Caspase-9 (CASP9).	[24]
Hydroquinone	DM6AVR4	Approved	Hydroquinone decreases the expression of Caspase-9 (CASP9).	[25]
Rosiglitazone	DMILWZR	Approved	Rosiglitazone increases the activity of Caspase-9 (CASP9).	[26]
Aspirin	DM672AH	Approved	Aspirin increases the activity of Caspase-9 (CASP9).	[28]
Etoposide	DMNH3PG	Approved	Etoposide increases the activity of Caspase-9 (CASP9).	[29]
Irinotecan	DMP6SC2	Approved	Irinotecan increases the activity of Caspase-9 (CASP9).	[30]
Paclitaxel	DMLB81S	Approved	Paclitaxel increases the expression of Caspase-9 (CASP9).	[31]
Diclofenac	DMPIHLS	Approved	Diclofenac increases the expression of Caspase-9 (CASP9).	[32]
Nicotine	DMWX5CO	Approved	Nicotine decreases the expression of Caspase-9 (CASP9).	[33]
Dasatinib	DMJV2EK	Approved	Dasatinib increases the activity of Caspase-9 (CASP9).	[34]
Indomethacin	DMSC4A7	Approved	Indomethacin increases the expression of Caspase-9 (CASP9).	[32]
Menthol	DMG2KW7	Approved	Menthol increases the expression of Caspase-9 (CASP9).	[36]
Mitomycin	DMH0ZJE	Approved	Mitomycin increases the activity of Caspase-9 (CASP9).	[37]
Cocaine	DMSOX7I	Approved	Cocaine increases the expression of Caspase-9 (CASP9).	[38]
Simvastatin	DM30SGU	Approved	Simvastatin decreases the activity of Caspase-9 (CASP9).	[39]
Gemcitabine	DMSE3I7	Approved	Gemcitabine increases the activity of Caspase-9 (CASP9).	[40]
Mitoxantrone	DMM39BF	Approved	Mitoxantrone increases the activity of Caspase-9 (CASP9).	[41]
Sulindac	DM2QHZU	Approved	Sulindac increases the activity of Caspase-9 (CASP9).	[42]
Capsaicin	DMGMF6V	Approved	Capsaicin increases the expression of Caspase-9 (CASP9).	[43]
Thalidomide	DM70BU5	Approved	Thalidomide decreases the activity of Caspase-9 (CASP9).	[45]
Colchicine	DM2POTE	Approved	Colchicine increases the activity of Caspase-9 (CASP9).	[46]
Sorafenib	DMS8IFC	Approved	Sorafenib increases the activity of Caspase-9 (CASP9).	[47]
Nefazodone	DM4ZS8M	Approved	Nefazodone increases the activity of Caspase-9 (CASP9).	[48]
Chenodiol	DMQ8JIK	Approved	Chenodiol increases the activity of Caspase-9 (CASP9).	[49]
Docetaxel	DMDI269	Approved	Docetaxel increases the activity of Caspase-9 (CASP9).	[50]
Cholecalciferol	DMGU74E	Approved	Cholecalciferol decreases the expression of Caspase-9 (CASP9).	[51]
Nitric Oxide	DM1RBYG	Approved	Nitric Oxide increases the activity of Caspase-9 (CASP9).	[52]
Lovastatin	DM9OZWQ	Approved	Lovastatin increases the activity of Caspase-9 (CASP9).	[53]
Melatonin	DMKWFBT	Approved	Melatonin increases the activity of Caspase-9 (CASP9).	[55]
Deoxycholic acid	DM3GYAL	Approved	Deoxycholic acid increases the activity of Caspase-9 (CASP9).	[56]
Artesunate	DMR27C8	Approved	Artesunate affects the expression of Caspase-9 (CASP9).	[57]
Isoniazid	DM5JVS3	Approved	Isoniazid increases the activity of Caspase-9 (CASP9).	[58]
Adenosine	DMM2NSK	Approved	Adenosine increases the activity of Caspase-9 (CASP9).	[59]
Gentamicin	DMKINJO	Approved	Gentamicin increases the expression of Caspase-9 (CASP9).	[60]
Morphine	DMRMS0L	Approved	Morphine increases the activity of Caspase-9 (CASP9).	[61]
Ciprofloxacin XR	DM2NLS9	Approved	Ciprofloxacin XR increases the activity of Caspase-9 (CASP9).	[62]
Cantharidin	DMBP5N3	Approved	Cantharidin increases the expression of Caspase-9 (CASP9).	[63]
Cimetidine	DMH61ZB	Approved	Cimetidine increases the activity of Caspase-9 (CASP9).	[64]
Lapatinib	DM3BH1Y	Approved	Lapatinib increases the activity of Caspase-9 (CASP9).	[67]
Masoprocol	DMMVNZ0	Approved	Masoprocol increases the activity of Caspase-9 (CASP9).	[70]
Phenylephrine	DMZHUO5	Approved	Phenylephrine increases the activity of Caspase-9 (CASP9).	[71]
Epirubicin	DMPDW6T	Approved	Epirubicin increases the expression of Caspase-9 (CASP9).	[72]
Sanguinarine	DMDINFS	Approved	Sanguinarine decreases the expression of Caspase-9 (CASP9).	[74]
Ketamine	DMT5HA4	Approved	Ketamine increases the activity of Caspase-9 (CASP9).	[76]
Budesonide	DMJIBAW	Approved	Budesonide increases the activity of Caspase-9 (CASP9).	[21]
Etodolac	DM6WJO9	Approved	Etodolac increases the activity of Caspase-9 (CASP9).	[77]
Methoxsalen	DME8FZ9	Approved	Methoxsalen decreases the expression of Caspase-9 (CASP9).	[78]
Ropivacaine	DMSPJG2	Approved	Ropivacaine decreases the expression of Caspase-9 (CASP9).	[80]
Clonidine	DM6RZ9Q	Approved	Clonidine increases the activity of Caspase-9 (CASP9).	[81]
Lidocaine	DML4ZOT	Approved	Lidocaine decreases the expression of Caspase-9 (CASP9).	[80]
Mechlorethamine	DM0CVXA	Approved	Mechlorethamine increases the activity of Caspase-9 (CASP9).	[83]
Cilostazol	DMZMSCT	Approved	Cilostazol increases the activity of Caspase-9 (CASP9).	[84]
Bupropion	DM5PCS7	Approved	Bupropion increases the activity of Caspase-9 (CASP9).	[85]
Cladribine	DM3JDRP	Approved	Cladribine increases the activity of Caspase-9 (CASP9).	[87]
Pyrimethamine	DM5X7VY	Approved	Pyrimethamine increases the activity of Caspase-9 (CASP9).	[88]
Riluzole	DMECBWN	Approved	Riluzole increases the activity of Caspase-9 (CASP9).	[89]
Acitretin	DM8BKU9	Approved	Acitretin increases the activity of Caspase-9 (CASP9).	[90]
Bendamustine hydrochloride	DMFH15Z	Approved	Bendamustine hydrochloride increases the activity of Caspase-9 (CASP9).	[41]
Bupivacaine	DM4PRFC	Approved	Bupivacaine decreases the expression of Caspase-9 (CASP9).	[80]
Aminolevulinic acid hci	DMS4BLQ	Approved	Aminolevulinic acid hci increases the activity of Caspase-9 (CASP9).	[92]
Trientine	DMD2WPG	Approved	Trientine increases the activity of Caspase-9 (CASP9).	[93]

18 Drug(s) Affected the Protein Interaction/Cellular Processes of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Temozolomide	DMKECZD	Approved	Temozolomide increases the cleavage of Caspase-9 (CASP9).	[8]
Decitabine	DMQL8XJ	Approved	Decitabine increases the cleavage of Caspase-9 (CASP9).	[16]
Menadione	DMSJDTY	Approved	Menadione increases the cleavage of Caspase-9 (CASP9).	[19]
Ethanol	DMDRQZU	Approved	Ethanol increases the cleavage of Caspase-9 (CASP9).	[27]
Malathion	DMXZ84M	Approved	Malathion increases the cleavage of Caspase-9 (CASP9).	[35]
Daunorubicin	DMQUSBT	Approved	Daunorubicin increases the cleavage of Caspase-9 (CASP9).	[44]
Propofol	DMB4OLE	Approved	Propofol increases the cleavage of Caspase-9 (CASP9).	[54]
Romidepsin	DMT5GNL	Approved	Romidepsin increases the cleavage of Caspase-9 (CASP9).	[65]
Nilotinib	DM7HXWT	Approved	Nilotinib increases the cleavage of Caspase-9 (CASP9).	[66]
Propranolol	DM79NTF	Approved	Propranolol increases the cleavage of Caspase-9 (CASP9).	[68]
Sulfasalazine	DMICA9H	Approved	Sulfasalazine increases the cleavage of Caspase-9 (CASP9).	[69]
Ethacrynic acid	DM60QMR	Approved	Ethacrynic acid increases the cleavage of Caspase-9 (CASP9).	[73]
Omacetaxine mepesuccinate	DMPU2WX	Approved	Omacetaxine mepesuccinate increases the cleavage of Caspase-9 (CASP9).	[75]
Loratadine	DMF3AN7	Approved	Loratadine increases the cleavage of Caspase-9 (CASP9).	[79]
Digitoxin	DMWVIGP	Approved	Digitoxin increases the cleavage of Caspase-9 (CASP9).	[82]
Pamidronate	DMB4AVP	Approved	Pamidronate increases the cleavage of Caspase-9 (CASP9).	[86]
Metoprolol	DMOJ0V6	Approved	Metoprolol increases the cleavage of Caspase-9 (CASP9).	[68]
Ceritinib	DMB920Z	Approved	Ceritinib increases the cleavage of Caspase-9 (CASP9).	[91]

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