Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTJWIVY0)

• DOT Name: Apoptotic protease-activating factor 1 (APAF1)
• Synonyms: APAF-1
• Gene Name: APAF1
• Related Disease:
  Lymphoma
  Acute leukaemia
  Acute lymphocytic leukaemia
  Acute myelogenous leukaemia
  Adult glioblastoma
  Advanced cancer
  B-cell neoplasm
  Bladder cancer
  Colon cancer
  Colorectal carcinoma
  Crohn disease
  Gastric cancer
  Glioblastoma multiforme
  Glioma
  Hepatocellular carcinoma
  Laryngeal carcinoma
  Leukemia
  Lung cancer
  Lung carcinoma
  Major depressive disorder
  Metastatic melanoma
  Ovarian cancer
  Papillary renal cell carcinoma
  Parkinson disease
  Plasma cell myeloma
  Renal cell carcinoma
  Small lymphocytic lymphoma
  Stomach cancer
  Urinary bladder cancer
  Urinary bladder neoplasm
  Breast cancer
  Breast carcinoma
  Cutaneous melanoma
  Tarsal-carpal coalition syndrome
  Adult lymphoma
  Clear cell renal carcinoma
  Depression
  Huntington disease
  Neuroblastoma
  Non-small-cell lung cancer
  Pediatric lymphoma
  Prostate cancer
  Prostate carcinoma
  Transitional cell carcinoma
• UniProt ID: APAF_HUMAN
• PDB ID: 1C15; 1CWW; 1CY5; 1Z6T; 2P1H; 2YGS; 3J2T; 3JBT; 3YGS; 4RHW; 5JUY; 5WVC; 5WVE
• Pfam ID: PF21296 ; PF17908 ; PF00619 ; PF00931 ; PF00400
• Sequence:
  MDAKARNCLLQHREALEKDIKTSYIMDHMISDGFLTISEEEKVRNEPTQQQRAAMLIKMI
  LKKDNDSYVSFYNALLHEGYKDLAALLHDGIPVVSSSSGKDSVSGITSYVRTVLCEGGVP
  QRPVVFVTRKKLVNAIQQKLSKLKGEPGWVTIHGMAGCGKSVLAAEAVRDHSLLEGCFPG
  GVHWVSVGKQDKSGLLMKLQNLCTRLDQDESFSQRLPLNIEEAKDRLRILMLRKHPRSLL
  ILDDVWDSWVLKAFDSQCQILLTTRDKSVTDSVMGPKYVVPVESSLGKEKGLEILSLFVN
  MKKADLPEQAHSIIKECKGSPLVVSLIGALLRDFPNRWEYYLKQLQNKQFKRIRKSSSYD
  YEALDEAMSISVEMLREDIKDYYTDLSILQKDVKVPTKVLCILWDMETEEVEDILQEFVN
  KSLLFCDRNGKSFRYYLHDLQVDFLTEKNCSQLQDLHKKIITQFQRYHQPHTLSPDQEDC
  MYWYNFLAYHMASAKMHKELCALMFSLDWIKAKTELVGPAHLIHEFVEYRHILDEKDCAV
  SENFQEFLSLNGHLLGRQPFPNIVQLGLCEPETSEVYQQAKLQAKQEVDNGMLYLEWINK
  KNITNLSRLVVRPHTDAVYHACFSEDGQRIASCGADKTLQVFKAETGEKLLEIKAHEDEV
  LCCAFSTDDRFIATCSVDKKVKIWNSMTGELVHTYDEHSEQVNCCHFTNSSHHLLLATGS
  SDCFLKLWDLNQKECRNTMFGHTNSVNHCRFSPDDKLLASCSADGTLKLWDATSANERKS
  INVKQFFLNLEDPQEDMEVIVKCCSWSADGARIMVAAKNKIFLFDIHTSGLLGEIHTGHH
  STIQYCDFSPQNHLAVVALSQYCVELWNTDSRSKVADCRGHLSWVHGVMFSPDGSSFLTS
  SDDQTIRLWETKKVCKNSAVMLKQEVDVVFQENEVMVLAVDHIRRLQLINGRTGQIDYLT
  EAQVSCCCLSPHLQYIAFGDENGAIEILELVNNRIFQSRFQHKKTVWHIQFTADEKTLIS
  SSDDAEIQVWNWQLDKCIFLRGHQETVKDFRLLKNSRLLSWSFDGTVKVWNIITGNKEKD
  FVCHQGTVLSCDISHDATKFSSTSADKTAKIWSFDLLLPLHELRGHNGCVRCSAFSVDST
  LLATGDDNGEIRIWNVSNGELLHLCAPLSEEGAATHGGWVTDLCFSPDGKMLISAGGYIK
  WWNVVTGESSQTFYTNGTNLKKIHVSPDFKTYVTVDNLGILYILQTLE
• Function: Oligomeric Apaf-1 mediates the cytochrome c-dependent autocatalytic activation of pro-caspase-9 (Apaf-3), leading to the activation of caspase-3 and apoptosis. This activation requires ATP. Isoform 6 is less effective in inducing apoptosis.
• Tissue Specificity: Ubiquitous. Highest levels of expression in adult spleen and peripheral blood leukocytes, and in fetal brain, kidney and lung. Isoform 1 is expressed in heart, kidney and liver.
• KEGG Pathway:
  Platinum drug resistance (hsa01524)
  p53 sig.ling pathway (hsa04115)
  Apoptosis (hsa04210)
  Apoptosis - multiple species (hsa04215)
  Alzheimer disease (hsa05010)
  Parkinson disease (hsa05012)
  Amyotrophic lateral sclerosis (hsa05014)
  Huntington disease (hsa05016)
  Prion disease (hsa05020)
  Pathways of neurodegeneration - multiple diseases (hsa05022)
  Legionellosis (hsa05134)
  Tuberculosis (hsa05152)
  Hepatitis C (hsa05160)
  Hepatitis B (hsa05161)
  Measles (hsa05162)
  Influenza A (hsa05164)
  Herpes simplex virus 1 infection (hsa05168)
  Epstein-Barr virus infection (hsa05169)
  Pathways in cancer (hsa05200)
  Small cell lung cancer (hsa05222)
  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)
  Neutrophil degranulation (R-HSA-6798695)
  TP53 Regulates Transcription of Caspase Activators and Caspases (R-HSA-6803207)
  Transcriptional Regulation by E2F6 (R-HSA-8953750)
  Regulation of the apoptosome activity (R-HSA-9627069)
  Formation of apoptosome (R-HSA-111458)

Molecular Interaction Atlas (MIA) of This DOT

44 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Lymphoma	DISN6V4S	Definitive	Biomarker	[1]
Acute leukaemia	DISDQFDI	Strong	Posttranslational Modification	[2]
Acute lymphocytic leukaemia	DISPX75S	Strong	Altered Expression	[3]
Acute myelogenous leukaemia	DISCSPTN	Strong	Biomarker	[4]
Adult glioblastoma	DISVP4LU	Strong	Biomarker	[5]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[6]
B-cell neoplasm	DISVY326	Strong	Altered Expression	[7]
Bladder cancer	DISUHNM0	Strong	Altered Expression	[8]
Colon cancer	DISVC52G	Strong	Therapeutic	[9]
Colorectal carcinoma	DIS5PYL0	Strong	Biomarker	[10]
Crohn disease	DIS2C5Q8	Strong	Genetic Variation	[11]
Gastric cancer	DISXGOUK	Strong	Altered Expression	[12]
Glioblastoma multiforme	DISK8246	Strong	Biomarker	[5]
Glioma	DIS5RPEH	Strong	Altered Expression	[13]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[6]
Laryngeal carcinoma	DISNHCIV	Strong	Altered Expression	[14]
Leukemia	DISNAKFL	Strong	Altered Expression	[15]
Lung cancer	DISCM4YA	Strong	Altered Expression	[16]
Lung carcinoma	DISTR26C	Strong	Altered Expression	[16]
Major depressive disorder	DIS4CL3X	Strong	Biomarker	[17]
Metastatic melanoma	DISSL43L	Strong	Genetic Variation	[18]
Ovarian cancer	DISZJHAP	Strong	Altered Expression	[19]
Papillary renal cell carcinoma	DIS25HBV	Strong	Biomarker	[20]
Parkinson disease	DISQVHKL	Strong	Biomarker	[21]
Plasma cell myeloma	DIS0DFZ0	Strong	Biomarker	[22]
Renal cell carcinoma	DISQZ2X8	Strong	Biomarker	[23]
Small lymphocytic lymphoma	DIS30POX	Strong	Altered Expression	[24]
Stomach cancer	DISKIJSX	Strong	Altered Expression	[12]
Urinary bladder cancer	DISDV4T7	Strong	Altered Expression	[8]
Urinary bladder neoplasm	DIS7HACE	Strong	Altered Expression	[8]
Breast cancer	DIS7DPX1	moderate	Altered Expression	[25]
Breast carcinoma	DIS2UE88	moderate	Altered Expression	[25]
Cutaneous melanoma	DIS3MMH9	moderate	Genetic Variation	[26]
Tarsal-carpal coalition syndrome	DISY90L2	moderate	Altered Expression	[27]
Adult lymphoma	DISK8IZR	Limited	Biomarker	[28]
Clear cell renal carcinoma	DISBXRFJ	Limited	Biomarker	[29]
Depression	DIS3XJ69	Limited	Autosomal dominant	[30]
Huntington disease	DISQPLA4	Limited	Altered Expression	[31]
Neuroblastoma	DISVZBI4	Limited	Biomarker	[32]
Non-small-cell lung cancer	DIS5Y6R9	Limited	Biomarker	[31]
Pediatric lymphoma	DIS51BK2	Limited	Biomarker	[28]
Prostate cancer	DISF190Y	Limited	Biomarker	[33]
Prostate carcinoma	DISMJPLE	Limited	Biomarker	[33]
Transitional cell carcinoma	DISWVVDR	Limited	Posttranslational Modification	[27]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of Apoptotic protease-activating factor 1 (APAF1).	[34]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Apoptotic protease-activating factor 1 (APAF1).	[35]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Apoptotic protease-activating factor 1 (APAF1).	[36]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Apoptotic protease-activating factor 1 (APAF1).	[37]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Apoptotic protease-activating factor 1 (APAF1).	[38]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Apoptotic protease-activating factor 1 (APAF1).	[39]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Apoptotic protease-activating factor 1 (APAF1).	[40]
Arsenic	DMTL2Y1	Approved	Arsenic increases the expression of Apoptotic protease-activating factor 1 (APAF1).	[41]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Apoptotic protease-activating factor 1 (APAF1).	[42]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Apoptotic protease-activating factor 1 (APAF1).	[43]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Apoptotic protease-activating factor 1 (APAF1).	[44]
Methotrexate	DM2TEOL	Approved	Methotrexate increases the expression of Apoptotic protease-activating factor 1 (APAF1).	[45]
Decitabine	DMQL8XJ	Approved	Decitabine increases the expression of Apoptotic protease-activating factor 1 (APAF1).	[15]
Zoledronate	DMIXC7G	Approved	Zoledronate increases the expression of Apoptotic protease-activating factor 1 (APAF1).	[47]
Fluorouracil	DMUM7HZ	Approved	Fluorouracil increases the expression of Apoptotic protease-activating factor 1 (APAF1).	[48]
Cannabidiol	DM0659E	Approved	Cannabidiol decreases the expression of Apoptotic protease-activating factor 1 (APAF1).	[49]
Rosiglitazone	DMILWZR	Approved	Rosiglitazone decreases the expression of Apoptotic protease-activating factor 1 (APAF1).	[50]
Aspirin	DM672AH	Approved	Aspirin increases the expression of Apoptotic protease-activating factor 1 (APAF1).	[51]
Paclitaxel	DMLB81S	Approved	Paclitaxel increases the expression of Apoptotic protease-activating factor 1 (APAF1).	[52]
Diclofenac	DMPIHLS	Approved	Diclofenac affects the expression of Apoptotic protease-activating factor 1 (APAF1).	[44]
Menthol	DMG2KW7	Approved	Menthol increases the expression of Apoptotic protease-activating factor 1 (APAF1).	[53]
Cyclophosphamide	DM4O2Z7	Approved	Cyclophosphamide decreases the expression of Apoptotic protease-activating factor 1 (APAF1).	[54]
Capsaicin	DMGMF6V	Approved	Capsaicin increases the expression of Apoptotic protease-activating factor 1 (APAF1).	[55]
Acocantherin	DM7JT24	Approved	Acocantherin increases the expression of Apoptotic protease-activating factor 1 (APAF1).	[56]
Isoproterenol	DMK7MEY	Approved	Isoproterenol increases the expression of Apoptotic protease-activating factor 1 (APAF1).	[57]
Cimetidine	DMH61ZB	Approved	Cimetidine increases the activity of Apoptotic protease-activating factor 1 (APAF1).	[58]
Momelotinib	DMF98Q0	Approved	Momelotinib increases the expression of Apoptotic protease-activating factor 1 (APAF1).	[59]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Apoptotic protease-activating factor 1 (APAF1).	[60]
Resveratrol	DM3RWXL	Phase 3	Resveratrol decreases the expression of Apoptotic protease-activating factor 1 (APAF1).	[61]
Epigallocatechin gallate	DMCGWBJ	Phase 3	Epigallocatechin gallate increases the expression of Apoptotic protease-activating factor 1 (APAF1).	[62]
Genistein	DM0JETC	Phase 2/3	Genistein increases the expression of Apoptotic protease-activating factor 1 (APAF1).	[63]
phorbol 12-myristate 13-acetate	DMJWD62	Phase 2	phorbol 12-myristate 13-acetate affects the expression of Apoptotic protease-activating factor 1 (APAF1).	[64]
PEITC	DMOMN31	Phase 2	PEITC increases the expression of Apoptotic protease-activating factor 1 (APAF1).	[65]
Tanespimycin	DMNLQHK	Phase 2	Tanespimycin increases the expression of Apoptotic protease-activating factor 1 (APAF1).	[66]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Apoptotic protease-activating factor 1 (APAF1).	[67]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 increases the expression of Apoptotic protease-activating factor 1 (APAF1).	[68]
AMEP	DMFELMQ	Phase 1	AMEP increases the expression of Apoptotic protease-activating factor 1 (APAF1).	[69]
HCV-796	DMPQSE4	Discontinued in Phase 2	HCV-796 increases the expression of Apoptotic protease-activating factor 1 (APAF1).	[70]
Dioscin	DM5H2W9	Preclinical	Dioscin decreases the expression of Apoptotic protease-activating factor 1 (APAF1).	[71]
WIN-55212-2	DMACBIW	Terminated	WIN-55212-2 decreases the expression of Apoptotic protease-activating factor 1 (APAF1).	[72]
Pifithrin-alpha	DM63OD7	Terminated	Pifithrin-alpha increases the expression of Apoptotic protease-activating factor 1 (APAF1).	[73]
L-709049	DMQZW6D	Terminated	L-709049 increases the expression of Apoptotic protease-activating factor 1 (APAF1).	[73]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Apoptotic protease-activating factor 1 (APAF1).	[74]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the activity of Apoptotic protease-activating factor 1 (APAF1).	[75]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Apoptotic protease-activating factor 1 (APAF1).	[76]
3R14S-OCHRATOXIN A	DM2KEW6	Investigative	3R14S-OCHRATOXIN A decreases the expression of Apoptotic protease-activating factor 1 (APAF1).	[77]
Paraquat	DMR8O3X	Investigative	Paraquat decreases the expression of Apoptotic protease-activating factor 1 (APAF1).	[78]
Glyphosate	DM0AFY7	Investigative	Glyphosate decreases the expression of Apoptotic protease-activating factor 1 (APAF1).	[79]
2-AMINO-1-METHYL-6-PHENYLIMIDAZO[4,5-B]PYRIDINE	DMNQL17	Investigative	2-AMINO-1-METHYL-6-PHENYLIMIDAZO[4,5-B]PYRIDINE decreases the expression of Apoptotic protease-activating factor 1 (APAF1).	[80]
Okadaic acid	DM47CO1	Investigative	Okadaic acid increases the expression of Apoptotic protease-activating factor 1 (APAF1).	[81]
Chlorpyrifos	DMKPUI6	Investigative	Chlorpyrifos increases the expression of Apoptotic protease-activating factor 1 (APAF1).	[82]
Cycloheximide	DMGDA3C	Investigative	Cycloheximide decreases the expression of Apoptotic protease-activating factor 1 (APAF1).	[83]
ELLAGIC ACID	DMX8BS5	Investigative	ELLAGIC ACID decreases the expression of Apoptotic protease-activating factor 1 (APAF1).	[61]
Morin	DM2OGZ5	Investigative	Morin increases the expression of Apoptotic protease-activating factor 1 (APAF1).	[84]
gingerol	DMNXYSM	Investigative	gingerol increases the expression of Apoptotic protease-activating factor 1 (APAF1).	[85]
Flavone	DMEQH6J	Investigative	Flavone increases the expression of Apoptotic protease-activating factor 1 (APAF1).	[86]
Bafilomycin A1	DMUNK59	Investigative	Bafilomycin A1 increases the expression of Apoptotic protease-activating factor 1 (APAF1).	[73]

References

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