Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTVO66BO)

• DOT Name: Protein NDRG1 (NDRG1)
• Synonyms: Differentiation-related gene 1 protein; DRG-1; N-myc downstream-regulated gene 1 protein; Nickel-specific induction protein Cap43; Reducing agents and tunicamycin-responsive protein; RTP; Rit42
• Gene Name: NDRG1
• Related Disease:
  Charcot-Marie-Tooth disease type 4D
  Advanced cancer
  Breast cancer
  Breast carcinoma
  Breast neoplasm
  Clear cell renal carcinoma
  Colorectal carcinoma
  Hepatocellular carcinoma
  Kidney cancer
  Kidney neoplasm
  Liver cancer
  Melanoma
  Metastatic malignant neoplasm
  Pancreatic cancer
  Papillary renal cell carcinoma
  Prostate carcinoma
  Prostate neoplasm
  Renal cell carcinoma
  Anaplastic astrocytoma
  Astrocytoma
  Charcot marie tooth disease
  Hemangioblastoma
  Hereditary motor and sensory neuropathy
  Oligoastrocytoma
  Small-cell lung cancer
  Charcot-Marie-Tooth disease type 3
  Charcot-Marie-Tooth disease type 4
  Glioblastoma multiforme
  Head-neck squamous cell carcinoma
  Neoplasm of oropharynx
  Non-small-cell lung cancer
  Oropharyngeal carcinoma
  Prostate cancer
• UniProt ID: NDRG1_HUMAN
• PDB ID: 6ZMM
• Pfam ID: PF03096
• Sequence:
  MSREMQDVDLAEVKPLVEKGETITGLLQEFDVQEQDIETLHGSVHVTLCGTPKGNRPVIL
  TYHDIGMNHKTCYNPLFNYEDMQEITQHFAVCHVDAPGQQDGAASFPAGYMYPSMDQLAE
  MLPGVLQQFGLKSIIGMGTGAGAYILTRFALNNPEMVEGLVLINVNPCAEGWMDWAASKI
  SGWTQALPDMVVSHLFGKEEMQSNVEVVHTYRQHIVNDMNPGNLHLFINAYNSRRDLEIE
  RPMPGTHTVTLQCPALLVVGDSSPAVDAVVECNSKLDPTKTTLLKMADCGGLPQISQPAK
  LAEAFKYFVQGMGYMPSASMTRLMRSRTASGSSVTSLDGTRSRSHTSEGTRSRSHTSEGT
  RSRSHTSEGAHLDITPNSGAAGNSAGPKSMEVSC
• Function: Stress-responsive protein involved in hormone responses, cell growth, and differentiation. Acts as a tumor suppressor in many cell types. Necessary but not sufficient for p53/TP53-mediated caspase activation and apoptosis. Has a role in cell trafficking, notably of the Schwann cell, and is necessary for the maintenance and development of the peripheral nerve myelin sheath. Required for vesicular recycling of CDH1 and TF. May also function in lipid trafficking. Protects cells from spindle disruption damage. Functions in p53/TP53-dependent mitotic spindle checkpoint. Regulates microtubule dynamics and maintains euploidy.
• Tissue Specificity: Ubiquitous; expressed most prominently in placental membranes and prostate, kidney, small intestine, and ovary tissues. Also expressed in heart, brain, skeletal muscle, lung, liver and pancreas. Low levels in peripheral blood leukocytes and in tissues of the immune system. Expressed mainly in epithelial cells. Also found in Schwann cells of peripheral neurons. Reduced expression in adenocarcinomas compared to normal tissues. In colon, prostate and placental membranes, the cells that border the lumen show the highest expression.
• Reactome Pathway: TP53 regulates transcription of several additional cell death genes whose specific roles in p53-dependent apoptosis remain uncertain (R-HSA-6803205)

Molecular Interaction Atlas (MIA) of This DOT

33 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Charcot-Marie-Tooth disease type 4D	DISGLJ7M	Definitive	Autosomal recessive	[1]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[2]
Breast cancer	DIS7DPX1	Strong	Biomarker	[3]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[3]
Breast neoplasm	DISNGJLM	Strong	Biomarker	[4]
Clear cell renal carcinoma	DISBXRFJ	Strong	Biomarker	[5]
Colorectal carcinoma	DIS5PYL0	Strong	Biomarker	[6]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[7]
Kidney cancer	DISBIPKM	Strong	Biomarker	[8]
Kidney neoplasm	DISBNZTN	Strong	Biomarker	[8]
Liver cancer	DISDE4BI	Strong	Altered Expression	[9]
Melanoma	DIS1RRCY	Strong	Altered Expression	[10]
Metastatic malignant neoplasm	DIS86UK6	Strong	Biomarker	[11]
Pancreatic cancer	DISJC981	Strong	Biomarker	[12]
Papillary renal cell carcinoma	DIS25HBV	Strong	Biomarker	[5]
Prostate carcinoma	DISMJPLE	Strong	Biomarker	[13]
Prostate neoplasm	DISHDKGQ	Strong	Altered Expression	[14]
Renal cell carcinoma	DISQZ2X8	Strong	Biomarker	[5]
Anaplastic astrocytoma	DISSBE0K	moderate	Biomarker	[8]
Astrocytoma	DISL3V18	moderate	Biomarker	[8]
Charcot marie tooth disease	DIS3BT2L	moderate	Genetic Variation	[15]
Hemangioblastoma	DIS1EAZC	moderate	Biomarker	[8]
Hereditary motor and sensory neuropathy	DISR0X2K	moderate	Biomarker	[16]
Oligoastrocytoma	DISQGE8F	moderate	Biomarker	[8]
Small-cell lung cancer	DISK3LZD	moderate	Biomarker	[8]
Charcot-Marie-Tooth disease type 3	DIS6DQK1	Limited	Biomarker	[17]
Charcot-Marie-Tooth disease type 4	DISM8IZN	Limited	CausalMutation	[18]
Glioblastoma multiforme	DISK8246	Limited	Altered Expression	[2]
Head-neck squamous cell carcinoma	DISF7P24	Limited	Biomarker	[19]
Neoplasm of oropharynx	DIS6YM4S	Limited	Biomarker	[19]
Non-small-cell lung cancer	DIS5Y6R9	Limited	Biomarker	[20]
Oropharyngeal carcinoma	DIS7K3AI	Limited	Biomarker	[19]
Prostate cancer	DISF190Y	Limited	Biomarker	[13]

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Irinotecan	DMP6SC2	Approved	Protein NDRG1 (NDRG1) decreases the response to substance of Irinotecan.	[68]

48 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 Protein NDRG1 (NDRG1).	[21]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Protein NDRG1 (NDRG1).	[22]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Protein NDRG1 (NDRG1).	[23]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Protein NDRG1 (NDRG1).	[24]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Protein NDRG1 (NDRG1).	[25]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Protein NDRG1 (NDRG1).	[26]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Protein NDRG1 (NDRG1).	[27]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Protein NDRG1 (NDRG1).	[28]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Protein NDRG1 (NDRG1).	[29]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide decreases the expression of Protein NDRG1 (NDRG1).	[30]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of Protein NDRG1 (NDRG1).	[31]
Decitabine	DMQL8XJ	Approved	Decitabine increases the expression of Protein NDRG1 (NDRG1).	[32]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of Protein NDRG1 (NDRG1).	[33]
Progesterone	DMUY35B	Approved	Progesterone increases the expression of Protein NDRG1 (NDRG1).	[34]
Menadione	DMSJDTY	Approved	Menadione affects the expression of Protein NDRG1 (NDRG1).	[35]
Niclosamide	DMJAGXQ	Approved	Niclosamide increases the expression of Protein NDRG1 (NDRG1).	[36]
Bortezomib	DMNO38U	Approved	Bortezomib increases the expression of Protein NDRG1 (NDRG1).	[37]
Troglitazone	DM3VFPD	Approved	Troglitazone increases the expression of Protein NDRG1 (NDRG1).	[38]
Azathioprine	DMMZSXQ	Approved	Azathioprine increases the expression of Protein NDRG1 (NDRG1).	[39]
Cytarabine	DMZD5QR	Approved	Cytarabine decreases the expression of Protein NDRG1 (NDRG1).	[40]
Ethinyl estradiol	DMODJ40	Approved	Ethinyl estradiol affects the expression of Protein NDRG1 (NDRG1).	[41]
Sulindac	DM2QHZU	Approved	Sulindac increases the expression of Protein NDRG1 (NDRG1).	[42]
Nitric Oxide	DM1RBYG	Approved	Nitric Oxide increases the expression of Protein NDRG1 (NDRG1).	[43]
Vandetanib	DMRICNP	Approved	Vandetanib increases the expression of Protein NDRG1 (NDRG1).	[44]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Protein NDRG1 (NDRG1).	[45]
Dihydrotestosterone	DM3S8XC	Phase 4	Dihydrotestosterone increases the expression of Protein NDRG1 (NDRG1).	[46]
Resveratrol	DM3RWXL	Phase 3	Resveratrol increases the expression of Protein NDRG1 (NDRG1).	[47]
Rigosertib	DMOSTXF	Phase 3	Rigosertib increases the expression of Protein NDRG1 (NDRG1).	[48]
Coprexa	DMA0WEK	Phase 3	Coprexa decreases the expression of Protein NDRG1 (NDRG1).	[49]
PEITC	DMOMN31	Phase 2	PEITC increases the expression of Protein NDRG1 (NDRG1).	[50]
ACYLINE	DM9GRTK	Phase 2	ACYLINE decreases the expression of Protein NDRG1 (NDRG1).	[51]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Protein NDRG1 (NDRG1).	[52]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 increases the expression of Protein NDRG1 (NDRG1).	[53]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Protein NDRG1 (NDRG1).	[54]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN increases the expression of Protein NDRG1 (NDRG1).	[56]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Protein NDRG1 (NDRG1).	[57]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane increases the expression of Protein NDRG1 (NDRG1).	[50]
chloropicrin	DMSGBQA	Investigative	chloropicrin affects the expression of Protein NDRG1 (NDRG1).	[58]
Deguelin	DMXT7WG	Investigative	Deguelin decreases the expression of Protein NDRG1 (NDRG1).	[59]
Nickel chloride	DMI12Y8	Investigative	Nickel chloride increases the expression of Protein NDRG1 (NDRG1).	[60]
Phencyclidine	DMQBEYX	Investigative	Phencyclidine increases the expression of Protein NDRG1 (NDRG1).	[61]
[3H]methyltrienolone	DMTSGOW	Investigative	[3H]methyltrienolone increases the expression of Protein NDRG1 (NDRG1).	[62]
OXYQUINOLINE	DMZVS9Y	Investigative	OXYQUINOLINE increases the expression of Protein NDRG1 (NDRG1).	[63]
Manganese	DMKT129	Investigative	Manganese increases the expression of Protein NDRG1 (NDRG1).	[64]
Resorcinol	DMM37C0	Investigative	Resorcinol increases the expression of Protein NDRG1 (NDRG1).	[39]
Nitrobenzanthrone	DMN6L70	Investigative	Nitrobenzanthrone decreases the expression of Protein NDRG1 (NDRG1).	[65]
Cycloheximide	DMGDA3C	Investigative	Cycloheximide decreases the expression of Protein NDRG1 (NDRG1).	[66]
2-(carboxymethylamino)-2-oxoacetic acid	DMQ2SNL	Investigative	2-(carboxymethylamino)-2-oxoacetic acid increases the expression of Protein NDRG1 (NDRG1).	[67]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 affects the phosphorylation of Protein NDRG1 (NDRG1).	[55]
Coumarin	DM0N8ZM	Investigative	Coumarin decreases the phosphorylation of Protein NDRG1 (NDRG1).	[55]

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