Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTXEE550)

• DOT Name: Phorbol-12-myristate-13-acetate-induced protein 1 (PMAIP1)
• Synonyms: PMA-induced protein 1; Immediate-early-response protein APR; Protein Noxa
• Gene Name: PMAIP1
• Related Disease:
  Myelodysplastic syndrome
  Acute lymphocytic leukaemia
  Acute monocytic leukemia
  B-cell lymphoma
  Breast cancer
  Breast carcinoma
  Burkitt lymphoma
  Cholangiocarcinoma
  Clear cell renal carcinoma
  Colorectal carcinoma
  Colorectal neoplasm
  Drug dependence
  Epithelial ovarian cancer
  Esophageal squamous cell carcinoma
  Head-neck squamous cell carcinoma
  HIV infectious disease
  leukaemia
  Leukemia
  Mantle cell lymphoma
  Matthew-Wood syndrome
  Neuroblastoma
  Ovarian cancer
  Ovarian neoplasm
  Pancreatic cancer
  Pancreatic tumour
  Plasma cell myeloma
  Promyelocytic leukaemia
  Prostate cancer
  Prostate carcinoma
  Pulmonary disease
  Renal cell carcinoma
  Small-cell lung cancer
  Substance abuse
  Substance dependence
  T-cell acute lymphoblastic leukaemia
  Transitional cell carcinoma
  Acute myelogenous leukaemia
  Coronary heart disease
  Hepatocellular carcinoma
  Non-small-cell lung cancer
  Obesity
  Triple negative breast cancer
  Non-insulin dependent diabetes
  B-cell neoplasm
  Lung cancer
  Lung carcinoma
  Melanoma
  Small lymphocytic lymphoma
  Stroke
• UniProt ID: APR_HUMAN
• PDB ID: 3MQP
• Pfam ID: PF15150
• Sequence: MPGKKARKNAQPSPARAPAELEVECATQLRRFGDKLNFRQKLLNLISKLFCSGT
• Function: Promotes activation of caspases and apoptosis. Promotes mitochondrial membrane changes and efflux of apoptogenic proteins from the mitochondria. Contributes to p53/TP53-dependent apoptosis after radiation exposure. Promotes proteasomal degradation of MCL1. Competes with BAK1 for binding to MCL1 and can displace BAK1 from its binding site on MCL1. Competes with BIM/BCL2L11 for binding to MCL1 and can displace BIM/BCL2L11 from its binding site on MCL1.
• Tissue Specificity: Highly expressed in adult T-cell leukemia cell line.
• KEGG Pathway:
  Platinum drug resistance (hsa01524)
  p53 sig.ling pathway (hsa04115)
  Apoptosis (hsa04210)
  Apoptosis - multiple species (hsa04215)
  Pathways in cancer (hsa05200)
  Viral carcinogenesis (hsa05203)
  Colorectal cancer (hsa05210)
• Reactome Pathway:
  BH3-only proteins associate with and inactivate anti-apoptotic BCL-2 members (R-HSA-111453)
  TP53 Regulates Transcription of Genes Involved in Cytochrome C Release (R-HSA-6803204)
  Activation of NOXA and translocation to mitochondria (R-HSA-111448)

Molecular Interaction Atlas (MIA) of This DOT

49 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Myelodysplastic syndrome	DISYHNUI	Definitive	Biomarker	[1]
Acute lymphocytic leukaemia	DISPX75S	Strong	Altered Expression	[2]
Acute monocytic leukemia	DIS28NEL	Strong	Altered Expression	[3]
B-cell lymphoma	DISIH1YQ	Strong	Biomarker	[4]
Breast cancer	DIS7DPX1	Strong	Altered Expression	[5]
Breast carcinoma	DIS2UE88	Strong	Altered Expression	[5]
Burkitt lymphoma	DIS9D5XU	Strong	Biomarker	[4]
Cholangiocarcinoma	DIS71F6X	Strong	Biomarker	[6]
Clear cell renal carcinoma	DISBXRFJ	Strong	Biomarker	[7]
Colorectal carcinoma	DIS5PYL0	Strong	Biomarker	[8]
Colorectal neoplasm	DISR1UCN	Strong	Altered Expression	[9]
Drug dependence	DIS9IXRC	Strong	Biomarker	[10]
Epithelial ovarian cancer	DIS56MH2	Strong	Biomarker	[11]
Esophageal squamous cell carcinoma	DIS5N2GV	Strong	Biomarker	[12]
Head-neck squamous cell carcinoma	DISF7P24	Strong	Altered Expression	[13]
HIV infectious disease	DISO97HC	Strong	Genetic Variation	[14]
leukaemia	DISS7D1V	Strong	Biomarker	[15]
Leukemia	DISNAKFL	Strong	Biomarker	[15]
Mantle cell lymphoma	DISFREOV	Strong	Altered Expression	[16]
Matthew-Wood syndrome	DISA7HR7	Strong	Biomarker	[17]
Neuroblastoma	DISVZBI4	Strong	Biomarker	[18]
Ovarian cancer	DISZJHAP	Strong	Biomarker	[11]
Ovarian neoplasm	DISEAFTY	Strong	Biomarker	[11]
Pancreatic cancer	DISJC981	Strong	Biomarker	[19]
Pancreatic tumour	DIS3U0LK	Strong	Biomarker	[19]
Plasma cell myeloma	DIS0DFZ0	Strong	Biomarker	[20]
Promyelocytic leukaemia	DISYGG13	Strong	Biomarker	[15]
Prostate cancer	DISF190Y	Strong	Biomarker	[11]
Prostate carcinoma	DISMJPLE	Strong	Biomarker	[11]
Pulmonary disease	DIS6060I	Strong	Biomarker	[21]
Renal cell carcinoma	DISQZ2X8	Strong	Biomarker	[7]
Small-cell lung cancer	DISK3LZD	Strong	Altered Expression	[22]
Substance abuse	DIS327VW	Strong	Biomarker	[10]
Substance dependence	DISDRAAR	Strong	Biomarker	[10]
T-cell acute lymphoblastic leukaemia	DIS17AI2	Strong	Altered Expression	[23]
Transitional cell carcinoma	DISWVVDR	Strong	Genetic Variation	[24]
Acute myelogenous leukaemia	DISCSPTN	moderate	Genetic Variation	[1]
Coronary heart disease	DIS5OIP1	moderate	Genetic Variation	[25]
Hepatocellular carcinoma	DIS0J828	moderate	Biomarker	[26]
Non-small-cell lung cancer	DIS5Y6R9	moderate	Biomarker	[27]
Obesity	DIS47Y1K	moderate	Genetic Variation	[25]
Triple negative breast cancer	DISAMG6N	moderate	Biomarker	[28]
Non-insulin dependent diabetes	DISK1O5Z	Disputed	Biomarker	[29]
B-cell neoplasm	DISVY326	Limited	Altered Expression	[30]
Lung cancer	DISCM4YA	Limited	Biomarker	[31]
Lung carcinoma	DISTR26C	Limited	Biomarker	[31]
Melanoma	DIS1RRCY	Limited	Genetic Variation	[32]
Small lymphocytic lymphoma	DIS30POX	Limited	Biomarker	[20]
Stroke	DISX6UHX	Limited	Altered Expression	[33]

This DOT Affected the Drug Response of 3 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Fluorouracil	DMUM7HZ	Approved	Phorbol-12-myristate-13-acetate-induced protein 1 (PMAIP1) affects the response to substance of Fluorouracil.	[106]
PMID26394986-Compound-22	DM43Z1G	Patented	Phorbol-12-myristate-13-acetate-induced protein 1 (PMAIP1) increases the response to substance of PMID26394986-Compound-22.	[107]
ABT-737	DML0DBV	Terminated	Phorbol-12-myristate-13-acetate-induced protein 1 (PMAIP1) increases the response to substance of ABT-737.	[108]

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 Phorbol-12-myristate-13-acetate-induced protein 1 (PMAIP1).	[34]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Phorbol-12-myristate-13-acetate-induced protein 1 (PMAIP1).	[35]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Phorbol-12-myristate-13-acetate-induced protein 1 (PMAIP1).	[36]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Phorbol-12-myristate-13-acetate-induced protein 1 (PMAIP1).	[37]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Phorbol-12-myristate-13-acetate-induced protein 1 (PMAIP1).	[38]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Phorbol-12-myristate-13-acetate-induced protein 1 (PMAIP1).	[39]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Phorbol-12-myristate-13-acetate-induced protein 1 (PMAIP1).	[40]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Phorbol-12-myristate-13-acetate-induced protein 1 (PMAIP1).	[41]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Phorbol-12-myristate-13-acetate-induced protein 1 (PMAIP1).	[42]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Phorbol-12-myristate-13-acetate-induced protein 1 (PMAIP1).	[43]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Phorbol-12-myristate-13-acetate-induced protein 1 (PMAIP1).	[44]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Phorbol-12-myristate-13-acetate-induced protein 1 (PMAIP1).	[45]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of Phorbol-12-myristate-13-acetate-induced protein 1 (PMAIP1).	[46]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of Phorbol-12-myristate-13-acetate-induced protein 1 (PMAIP1).	[47]
Methotrexate	DM2TEOL	Approved	Methotrexate increases the expression of Phorbol-12-myristate-13-acetate-induced protein 1 (PMAIP1).	[48]
Decitabine	DMQL8XJ	Approved	Decitabine affects the expression of Phorbol-12-myristate-13-acetate-induced protein 1 (PMAIP1).	[49]
Marinol	DM70IK5	Approved	Marinol decreases the expression of Phorbol-12-myristate-13-acetate-induced protein 1 (PMAIP1).	[50]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of Phorbol-12-myristate-13-acetate-induced protein 1 (PMAIP1).	[51]
Menadione	DMSJDTY	Approved	Menadione affects the expression of Phorbol-12-myristate-13-acetate-induced protein 1 (PMAIP1).	[45]
Demecolcine	DMCZQGK	Approved	Demecolcine increases the expression of Phorbol-12-myristate-13-acetate-induced protein 1 (PMAIP1).	[52]
Cannabidiol	DM0659E	Approved	Cannabidiol increases the expression of Phorbol-12-myristate-13-acetate-induced protein 1 (PMAIP1).	[53]
Bortezomib	DMNO38U	Approved	Bortezomib decreases the expression of Phorbol-12-myristate-13-acetate-induced protein 1 (PMAIP1).	[54]
Troglitazone	DM3VFPD	Approved	Troglitazone decreases the expression of Phorbol-12-myristate-13-acetate-induced protein 1 (PMAIP1).	[55]
Ethanol	DMDRQZU	Approved	Ethanol increases the expression of Phorbol-12-myristate-13-acetate-induced protein 1 (PMAIP1).	[56]
Aspirin	DM672AH	Approved	Aspirin increases the expression of Phorbol-12-myristate-13-acetate-induced protein 1 (PMAIP1).	[57]
Etoposide	DMNH3PG	Approved	Etoposide increases the expression of Phorbol-12-myristate-13-acetate-induced protein 1 (PMAIP1).	[58]
Irinotecan	DMP6SC2	Approved	Irinotecan increases the expression of Phorbol-12-myristate-13-acetate-induced protein 1 (PMAIP1).	[59]
Indomethacin	DMSC4A7	Approved	Indomethacin increases the expression of Phorbol-12-myristate-13-acetate-induced protein 1 (PMAIP1).	[60]
Amphotericin B	DMTAJQE	Approved	Amphotericin B increases the expression of Phorbol-12-myristate-13-acetate-induced protein 1 (PMAIP1).	[61]
Ethinyl estradiol	DMODJ40	Approved	Ethinyl estradiol affects the expression of Phorbol-12-myristate-13-acetate-induced protein 1 (PMAIP1).	[62]
Cidofovir	DMA13GD	Approved	Cidofovir affects the expression of Phorbol-12-myristate-13-acetate-induced protein 1 (PMAIP1).	[40]
Simvastatin	DM30SGU	Approved	Simvastatin increases the expression of Phorbol-12-myristate-13-acetate-induced protein 1 (PMAIP1).	[63]
Clodronate	DM9Y6X7	Approved	Clodronate decreases the expression of Phorbol-12-myristate-13-acetate-induced protein 1 (PMAIP1).	[40]
Acetic Acid, Glacial	DM4SJ5Y	Approved	Acetic Acid, Glacial increases the expression of Phorbol-12-myristate-13-acetate-induced protein 1 (PMAIP1).	[64]
Motexafin gadolinium	DMEJKRF	Approved	Motexafin gadolinium increases the expression of Phorbol-12-myristate-13-acetate-induced protein 1 (PMAIP1).	[64]
Sorafenib	DMS8IFC	Approved	Sorafenib decreases the expression of Phorbol-12-myristate-13-acetate-induced protein 1 (PMAIP1).	[65]
Adefovir dipivoxil	DMMAWY1	Approved	Adefovir dipivoxil increases the expression of Phorbol-12-myristate-13-acetate-induced protein 1 (PMAIP1).	[40]
Nefazodone	DM4ZS8M	Approved	Nefazodone increases the expression of Phorbol-12-myristate-13-acetate-induced protein 1 (PMAIP1).	[66]
Dihydroartemisinin	DMBXVMZ	Approved	Dihydroartemisinin increases the expression of Phorbol-12-myristate-13-acetate-induced protein 1 (PMAIP1).	[67]
Nitric Oxide	DM1RBYG	Approved	Nitric Oxide increases the expression of Phorbol-12-myristate-13-acetate-induced protein 1 (PMAIP1).	[68]
Isoproterenol	DMK7MEY	Approved	Isoproterenol increases the expression of Phorbol-12-myristate-13-acetate-induced protein 1 (PMAIP1).	[69]
Gentamicin	DMKINJO	Approved	Gentamicin increases the expression of Phorbol-12-myristate-13-acetate-induced protein 1 (PMAIP1).	[70]
Penicillamine	DM40EF6	Approved	Penicillamine increases the expression of Phorbol-12-myristate-13-acetate-induced protein 1 (PMAIP1).	[71]
Promethazine	DM6I5GR	Approved	Promethazine increases the expression of Phorbol-12-myristate-13-acetate-induced protein 1 (PMAIP1).	[72]
Pitavastatin	DMJH792	Approved	Pitavastatin increases the expression of Phorbol-12-myristate-13-acetate-induced protein 1 (PMAIP1).	[73]
Venetoclax	DM8I94Y	Approved	Venetoclax increases the expression of Phorbol-12-myristate-13-acetate-induced protein 1 (PMAIP1).	[74]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Phorbol-12-myristate-13-acetate-induced protein 1 (PMAIP1).	[75]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Phorbol-12-myristate-13-acetate-induced protein 1 (PMAIP1).	[76]
Resveratrol	DM3RWXL	Phase 3	Resveratrol increases the expression of Phorbol-12-myristate-13-acetate-induced protein 1 (PMAIP1).	[77]
Curcumin	DMQPH29	Phase 3	Curcumin increases the expression of Phorbol-12-myristate-13-acetate-induced protein 1 (PMAIP1).	[78]
Fenretinide	DMRD5SP	Phase 3	Fenretinide increases the expression of Phorbol-12-myristate-13-acetate-induced protein 1 (PMAIP1).	[79]
Rigosertib	DMOSTXF	Phase 3	Rigosertib increases the expression of Phorbol-12-myristate-13-acetate-induced protein 1 (PMAIP1).	[80]
MLN4924	DMP36KD	Phase 3	MLN4924 affects the expression of Phorbol-12-myristate-13-acetate-induced protein 1 (PMAIP1).	[81]
Genistein	DM0JETC	Phase 2/3	Genistein affects the expression of Phorbol-12-myristate-13-acetate-induced protein 1 (PMAIP1).	[82]
DNCB	DMDTVYC	Phase 2	DNCB increases the expression of Phorbol-12-myristate-13-acetate-induced protein 1 (PMAIP1).	[56]
APR-246	DMNFADH	Phase 2	APR-246 increases the expression of Phorbol-12-myristate-13-acetate-induced protein 1 (PMAIP1).	[83]
INCB057643	DMG65CV	Phase 1/2	INCB057643 increases the expression of Phorbol-12-myristate-13-acetate-induced protein 1 (PMAIP1).	[84]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Phorbol-12-myristate-13-acetate-induced protein 1 (PMAIP1).	[85]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Phorbol-12-myristate-13-acetate-induced protein 1 (PMAIP1).	[86]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide increases the expression of Phorbol-12-myristate-13-acetate-induced protein 1 (PMAIP1).	[87]
AMEP	DMFELMQ	Phase 1	AMEP increases the expression of Phorbol-12-myristate-13-acetate-induced protein 1 (PMAIP1).	[88]
AMG 176	DM0Q7NO	Phase 1	AMG 176 decreases the expression of Phorbol-12-myristate-13-acetate-induced protein 1 (PMAIP1).	[89]
AZD5991	DM7QGHO	Phase 1	AZD5991 decreases the expression of Phorbol-12-myristate-13-acetate-induced protein 1 (PMAIP1).	[89]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Phorbol-12-myristate-13-acetate-induced protein 1 (PMAIP1).	[90]
Eugenol	DM7US1H	Patented	Eugenol increases the expression of Phorbol-12-myristate-13-acetate-induced protein 1 (PMAIP1).	[56]
Torcetrapib	DMDHYM7	Discontinued in Phase 2	Torcetrapib increases the expression of Phorbol-12-myristate-13-acetate-induced protein 1 (PMAIP1).	[91]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN increases the expression of Phorbol-12-myristate-13-acetate-induced protein 1 (PMAIP1).	[79]
MG-132	DMKA2YS	Preclinical	MG-132 increases the expression of Phorbol-12-myristate-13-acetate-induced protein 1 (PMAIP1).	[92]
Pifithrin-alpha	DM63OD7	Terminated	Pifithrin-alpha decreases the expression of Phorbol-12-myristate-13-acetate-induced protein 1 (PMAIP1).	[93]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Phorbol-12-myristate-13-acetate-induced protein 1 (PMAIP1).	[94]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Phorbol-12-myristate-13-acetate-induced protein 1 (PMAIP1).	[95]
Milchsaure	DM462BT	Investigative	Milchsaure increases the expression of Phorbol-12-myristate-13-acetate-induced protein 1 (PMAIP1).	[96]
3R14S-OCHRATOXIN A	DM2KEW6	Investigative	3R14S-OCHRATOXIN A decreases the expression of Phorbol-12-myristate-13-acetate-induced protein 1 (PMAIP1).	[97]
Paraquat	DMR8O3X	Investigative	Paraquat increases the expression of Phorbol-12-myristate-13-acetate-induced protein 1 (PMAIP1).	[98]
Glyphosate	DM0AFY7	Investigative	Glyphosate increases the expression of Phorbol-12-myristate-13-acetate-induced protein 1 (PMAIP1).	[88]
Nickel chloride	DMI12Y8	Investigative	Nickel chloride increases the expression of Phorbol-12-myristate-13-acetate-induced protein 1 (PMAIP1).	[99]
Phencyclidine	DMQBEYX	Investigative	Phencyclidine increases the expression of Phorbol-12-myristate-13-acetate-induced protein 1 (PMAIP1).	[100]
Lithium chloride	DMHYLQ2	Investigative	Lithium chloride increases the expression of Phorbol-12-myristate-13-acetate-induced protein 1 (PMAIP1).	[101]
cinnamaldehyde	DMZDUXG	Investigative	cinnamaldehyde increases the expression of Phorbol-12-myristate-13-acetate-induced protein 1 (PMAIP1).	[56]
Arachidonic acid	DMUOQZD	Investigative	Arachidonic acid increases the expression of Phorbol-12-myristate-13-acetate-induced protein 1 (PMAIP1).	[102]
PATULIN	DM0RV9C	Investigative	PATULIN increases the expression of Phorbol-12-myristate-13-acetate-induced protein 1 (PMAIP1).	[103]
Phenanthrene-9,10-dione	DMG8KS9	Investigative	Phenanthrene-9,10-dione increases the expression of Phorbol-12-myristate-13-acetate-induced protein 1 (PMAIP1).	[104]
N-(3-METHYLBUT-2-EN-1-YL)-9H-PURIN-6-AMINE	DM2D4KY	Investigative	N-(3-METHYLBUT-2-EN-1-YL)-9H-PURIN-6-AMINE increases the expression of Phorbol-12-myristate-13-acetate-induced protein 1 (PMAIP1).	[105]
benzyl bromide	DM857X2	Investigative	benzyl bromide increases the expression of Phorbol-12-myristate-13-acetate-induced protein 1 (PMAIP1).	[56]
N-dodecylgallate	DMV5RZM	Investigative	N-dodecylgallate increases the expression of Phorbol-12-myristate-13-acetate-induced protein 1 (PMAIP1).	[56]

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