Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTZ6NXUX)

• DOT Name: Programmed cell death protein 4 (PDCD4)
• Synonyms: Neoplastic transformation inhibitor protein; Nuclear antigen H731-like; Protein 197/15a
• Gene Name: PDCD4
• Related Disease:
  Glioma
  Lung cancer
  Ovarian cancer
  Acute myelogenous leukaemia
  Adenoma
  Advanced cancer
  Alzheimer disease
  B-cell neoplasm
  Bladder cancer
  Bone osteosarcoma
  Breast cancer
  Breast carcinoma
  Carcinoma
  Carcinoma of esophagus
  Colon carcinoma
  Coronary atherosclerosis
  Epithelial ovarian cancer
  Esophageal cancer
  Glioblastoma multiforme
  Head-neck squamous cell carcinoma
  Hepatocellular carcinoma
  Laryngeal squamous cell carcinoma
  Lung carcinoma
  Nasopharyngeal carcinoma
  Neoplasm of esophagus
  Non-small-cell lung cancer
  Osteosarcoma
  Ovarian neoplasm
  Polycystic ovarian syndrome
  Prostate cancer
  Prostate carcinoma
  Squamous cell carcinoma
  Adult glioblastoma
  Colon cancer
  Colorectal carcinoma
  Thyroid gland papillary carcinoma
  Triple negative breast cancer
  Endometriosis
  Lung neoplasm
  Breast neoplasm
  Clear cell renal carcinoma
  Endometrial cancer
  Endometrial carcinoma
  Melanoma
  Myocardial infarction
  Obesity
  Pancreatic cancer
  Renal cell carcinoma
• UniProt ID: PDCD4_HUMAN
• PDB ID: 2GGF; 2KZT; 2RG8; 2ZU6; 3EIJ
• Pfam ID: PF02847
• Sequence:
  MDVENEQILNVNPADPDNLSDSLFSGDEENAGTEEIKNEINGNWISASSINEARINAKAK
  RRLRKNSSRDSGRGDSVSDSGSDALRSGLTVPTSPKGRLLDRRSRSGKGRGLPKKGGAGG
  KGVWGTPGQVYDVEEVDVKDPNYDDDQENCVYETVVLPLDERAFEKTLTPIIQEYFEHGD
  TNEVAEMLRDLNLGEMKSGVPVLAVSLALEGKASHREMTSKLLSDLCGTVMSTTDVEKSF
  DKLLKDLPELALDTPRAPQLVGQFIARAVGDGILCNTYIDSYKGTVDCVQARAALDKATV
  LLSMSKGGKRKDSVWGSGGGQQSVNHLVKEIDMLLKEYLLSGDISEAEHCLKELEVPHFH
  HELVYEAIIMVLESTGESTFKMILDLLKSLWKSSTITVDQMKRGYERIYNEIPDINLDVP
  HSYSVLERFVEECFQAGIISKQLRDLCPSRGRKRFVSEGDGGRLKPESY
• Function: Inhibits translation initiation and cap-dependent translation. May excert its function by hindering the interaction between EIF4A1 and EIF4G. Inhibits the helicase activity of EIF4A. Modulates the activation of JUN kinase. Down-regulates the expression of MAP4K1, thus inhibiting events important in driving invasion, namely, MAPK85 activation and consequent JUN-dependent transcription. May play a role in apoptosis. Tumor suppressor. Inhibits tumor promoter-induced neoplastic transformation. Binds RNA.
• Tissue Specificity: Up-regulated in proliferative cells. Highly expressed in epithelial cells of the mammary gland. Reduced expression in lung cancer and colon carcinoma.
• KEGG Pathway:
  Proteoglycans in cancer (hsa05205)
  MicroR.s in cancer (hsa05206)
• Reactome Pathway: Gene and protein expression by JAK-STAT signaling after Interleukin-12 stimulation (R-HSA-8950505)

Molecular Interaction Atlas (MIA) of This DOT

48 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Glioma	DIS5RPEH	Definitive	Biomarker	[1]
Lung cancer	DISCM4YA	Definitive	Biomarker	[2]
Ovarian cancer	DISZJHAP	Definitive	Biomarker	[3]
Acute myelogenous leukaemia	DISCSPTN	Strong	Biomarker	[4]
Adenoma	DIS78ZEV	Strong	Biomarker	[5]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[6]
Alzheimer disease	DISF8S70	Strong	Biomarker	[7]
B-cell neoplasm	DISVY326	Strong	Altered Expression	[8]
Bladder cancer	DISUHNM0	Strong	Biomarker	[9]
Bone osteosarcoma	DIST1004	Strong	Altered Expression	[10]
Breast cancer	DIS7DPX1	Strong	Biomarker	[11]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[11]
Carcinoma	DISH9F1N	Strong	Altered Expression	[12]
Carcinoma of esophagus	DISS6G4D	Strong	Biomarker	[13]
Colon carcinoma	DISJYKUO	Strong	Biomarker	[14]
Coronary atherosclerosis	DISKNDYU	Strong	Biomarker	[15]
Epithelial ovarian cancer	DIS56MH2	Strong	Biomarker	[3]
Esophageal cancer	DISGB2VN	Strong	Biomarker	[13]
Glioblastoma multiforme	DISK8246	Strong	Biomarker	[16]
Head-neck squamous cell carcinoma	DISF7P24	Strong	Altered Expression	[17]
Hepatocellular carcinoma	DIS0J828	Strong	Altered Expression	[18]
Laryngeal squamous cell carcinoma	DIS9UUVF	Strong	Biomarker	[19]
Lung carcinoma	DISTR26C	Strong	Altered Expression	[20]
Nasopharyngeal carcinoma	DISAOTQ0	Strong	Altered Expression	[21]
Neoplasm of esophagus	DISOLKAQ	Strong	Biomarker	[13]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Altered Expression	[22]
Osteosarcoma	DISLQ7E2	Strong	Altered Expression	[10]
Ovarian neoplasm	DISEAFTY	Strong	Biomarker	[3]
Polycystic ovarian syndrome	DISZ2BNG	Strong	Altered Expression	[23]
Prostate cancer	DISF190Y	Strong	Altered Expression	[24]
Prostate carcinoma	DISMJPLE	Strong	Altered Expression	[24]
Squamous cell carcinoma	DISQVIFL	Strong	Biomarker	[25]
Adult glioblastoma	DISVP4LU	moderate	Biomarker	[16]
Colon cancer	DISVC52G	moderate	Biomarker	[14]
Colorectal carcinoma	DIS5PYL0	moderate	Biomarker	[26]
Thyroid gland papillary carcinoma	DIS48YMM	moderate	Altered Expression	[27]
Triple negative breast cancer	DISAMG6N	moderate	Altered Expression	[28]
Endometriosis	DISX1AG8	Disputed	Altered Expression	[29]
Lung neoplasm	DISVARNB	Disputed	Biomarker	[2]
Breast neoplasm	DISNGJLM	Limited	Altered Expression	[30]
Clear cell renal carcinoma	DISBXRFJ	Limited	Altered Expression	[31]
Endometrial cancer	DISW0LMR	Limited	Altered Expression	[29]
Endometrial carcinoma	DISXR5CY	Limited	Altered Expression	[29]
Melanoma	DIS1RRCY	Limited	Biomarker	[32]
Myocardial infarction	DIS655KI	Limited	Altered Expression	[33]
Obesity	DIS47Y1K	Limited	Altered Expression	[34]
Pancreatic cancer	DISJC981	Limited	Altered Expression	[35]
Renal cell carcinoma	DISQZ2X8	Limited	Altered Expression	[31]

6 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 Programmed cell death protein 4 (PDCD4).	[36]
Arsenic	DMTL2Y1	Approved	Arsenic increases the methylation of Programmed cell death protein 4 (PDCD4).	[41]
TAK-243	DM4GKV2	Phase 1	TAK-243 increases the sumoylation of Programmed cell death protein 4 (PDCD4).	[64]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 affects the phosphorylation of Programmed cell death protein 4 (PDCD4).	[65]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Programmed cell death protein 4 (PDCD4).	[67]
Coumarin	DM0N8ZM	Investigative	Coumarin decreases the phosphorylation of Programmed cell death protein 4 (PDCD4).	[65]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Programmed cell death protein 4 (PDCD4).	[37]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Programmed cell death protein 4 (PDCD4).	[38]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Programmed cell death protein 4 (PDCD4).	[39]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Programmed cell death protein 4 (PDCD4).	[40]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Programmed cell death protein 4 (PDCD4).	[42]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Programmed cell death protein 4 (PDCD4).	[43]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Programmed cell death protein 4 (PDCD4).	[44]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Programmed cell death protein 4 (PDCD4).	[45]
Phenobarbital	DMXZOCG	Approved	Phenobarbital decreases the expression of Programmed cell death protein 4 (PDCD4).	[46]
Progesterone	DMUY35B	Approved	Progesterone increases the expression of Programmed cell death protein 4 (PDCD4).	[47]
Menadione	DMSJDTY	Approved	Menadione affects the expression of Programmed cell death protein 4 (PDCD4).	[43]
Fluorouracil	DMUM7HZ	Approved	Fluorouracil decreases the expression of Programmed cell death protein 4 (PDCD4).	[48]
Niclosamide	DMJAGXQ	Approved	Niclosamide increases the expression of Programmed cell death protein 4 (PDCD4).	[49]
Hydroquinone	DM6AVR4	Approved	Hydroquinone decreases the expression of Programmed cell death protein 4 (PDCD4).	[50]
Diethylstilbestrol	DMN3UXQ	Approved	Diethylstilbestrol increases the expression of Programmed cell death protein 4 (PDCD4).	[51]
Testosterone enanthate	DMB6871	Approved	Testosterone enanthate affects the expression of Programmed cell death protein 4 (PDCD4).	[52]
Diclofenac	DMPIHLS	Approved	Diclofenac decreases the expression of Programmed cell death protein 4 (PDCD4).	[46]
Ethinyl estradiol	DMODJ40	Approved	Ethinyl estradiol affects the expression of Programmed cell death protein 4 (PDCD4).	[53]
Cyclophosphamide	DM4O2Z7	Approved	Cyclophosphamide decreases the expression of Programmed cell death protein 4 (PDCD4).	[46]
Acetic Acid, Glacial	DM4SJ5Y	Approved	Acetic Acid, Glacial increases the expression of Programmed cell death protein 4 (PDCD4).	[54]
Motexafin gadolinium	DMEJKRF	Approved	Motexafin gadolinium increases the expression of Programmed cell death protein 4 (PDCD4).	[54]
Lindane	DMB8CNL	Approved	Lindane increases the expression of Programmed cell death protein 4 (PDCD4).	[55]
Prednisolone	DMQ8FR2	Approved	Prednisolone increases the expression of Programmed cell death protein 4 (PDCD4).	[55]
Nifedipine	DMSVOZT	Approved	Nifedipine decreases the expression of Programmed cell death protein 4 (PDCD4).	[46]
Prasterone	DM67VKL	Approved	Prasterone decreases the expression of Programmed cell death protein 4 (PDCD4).	[56]
Clonidine	DM6RZ9Q	Approved	Clonidine decreases the expression of Programmed cell death protein 4 (PDCD4).	[46]
Tolbutamide	DM02AWV	Approved	Tolbutamide decreases the expression of Programmed cell death protein 4 (PDCD4).	[46]
Mannitol	DMSCDY9	Approved	Mannitol decreases the expression of Programmed cell death protein 4 (PDCD4).	[46]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Programmed cell death protein 4 (PDCD4).	[57]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 decreases the expression of Programmed cell death protein 4 (PDCD4).	[58]
Resveratrol	DM3RWXL	Phase 3	Resveratrol increases the expression of Programmed cell death protein 4 (PDCD4).	[59]
Genistein	DM0JETC	Phase 2/3	Genistein increases the expression of Programmed cell death protein 4 (PDCD4).	[60]
GSK2110183	DMZHB37	Phase 2	GSK2110183 increases the expression of Programmed cell death protein 4 (PDCD4).	[61]
Afimoxifene	DMFORDT	Phase 2	Afimoxifene decreases the expression of Programmed cell death protein 4 (PDCD4).	[62]
phorbol 12-myristate 13-acetate	DMJWD62	Phase 2	phorbol 12-myristate 13-acetate decreases the expression of Programmed cell death protein 4 (PDCD4).	[46]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Programmed cell death protein 4 (PDCD4).	[46]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide decreases the expression of Programmed cell death protein 4 (PDCD4).	[63]
LY294002	DMY1AFS	Phase 1	LY294002 increases the expression of Programmed cell death protein 4 (PDCD4).	[38]
GSK618334	DMJPXZ4	Phase 1	GSK618334 increases the expression of Programmed cell death protein 4 (PDCD4).	[55]
PIRINIXIC ACID	DM82Y75	Preclinical	PIRINIXIC ACID decreases the expression of Programmed cell death protein 4 (PDCD4).	[46]
NS398	DMINUWH	Terminated	NS398 increases the expression of Programmed cell death protein 4 (PDCD4).	[66]
Wortmannin	DM8EVK5	Terminated	Wortmannin increases the expression of Programmed cell death protein 4 (PDCD4).	[38]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Programmed cell death protein 4 (PDCD4).	[68]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Programmed cell death protein 4 (PDCD4).	[69]
Coumestrol	DM40TBU	Investigative	Coumestrol increases the expression of Programmed cell death protein 4 (PDCD4).	[39]
3R14S-OCHRATOXIN A	DM2KEW6	Investigative	3R14S-OCHRATOXIN A decreases the expression of Programmed cell death protein 4 (PDCD4).	[70]
Phencyclidine	DMQBEYX	Investigative	Phencyclidine decreases the expression of Programmed cell death protein 4 (PDCD4).	[71]
Rapamycin Immunosuppressant Drug	DM678IB	Investigative	Rapamycin Immunosuppressant Drug increases the expression of Programmed cell death protein 4 (PDCD4).	[38]
BRN-3548355	DM4KXT0	Investigative	BRN-3548355 decreases the expression of Programmed cell death protein 4 (PDCD4).	[46]
propylpyrazoletriol	DMTCP8K	Investigative	propylpyrazoletriol increases the expression of Programmed cell death protein 4 (PDCD4).	[72]
diarylpropionitril	DM14X29	Investigative	diarylpropionitril decreases the expression of Programmed cell death protein 4 (PDCD4).	[72]

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