Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT8S1RRP)

• DOT Name: Metalloproteinase inhibitor 2 (TIMP2)
• Synonyms: CSC-21K; Tissue inhibitor of metalloproteinases 2; TIMP-2
• Gene Name: TIMP2
• Related Disease:
  Atrial fibrillation
  Pancreatic cancer
  Acute myelogenous leukaemia
  Adenocarcinoma
  Adult glioblastoma
  Alzheimer disease
  Bladder cancer
  Breast cancer
  Breast carcinoma
  Cardiomyopathy
  Cervical cancer
  Cervical carcinoma
  Chronic obstructive pulmonary disease
  Diabetic kidney disease
  Eosinophilic esophagitis
  Fibrosarcoma
  Gastric cancer
  Glioblastoma multiforme
  Glioma
  Hepatocellular carcinoma
  Idiopathic cardiomyopathy
  Myocardial infarction
  Non-small-cell lung cancer
  Osteoarthritis
  Plasma cell myeloma
  Urinary bladder cancer
  Urinary bladder neoplasm
  Breast neoplasm
  Lung cancer
  Lung carcinoma
  Squamous cell carcinoma
  Stomach cancer
  Abdominal aortic aneurysm
  Bone osteosarcoma
  Calcinosis
  Endometriosis
  Familial tumoral calcinosis
  Melanoma
  Neuroblastoma
  Osteosarcoma
  Pleural disease
  Type-1/2 diabetes
• UniProt ID: TIMP2_HUMAN
• PDB ID: 1BR9; 1GXD; 2TMP; 4ILW
• Pfam ID: PF00965
• Sequence:
  MGAAARTLRLALGLLLLATLLRPADACSCSPVHPQQAFCNADVVIRAKAVSEKEVDSGND
  IYGNPIKRIQYEIKQIKMFKGPEKDIEFIYTAPSSAVCGVSLDVGGKKEYLIAGKAEGDG
  KMHITLCDFIVPWDTLSTTQKKSLNHRYQMGCECKITRCPMIPCYISSPDECLWMDWVTE
  KNINGHQAKFFACIKRSDGSCAWYRGAAPPKQEFLDIEDP
• Function: Complexes with metalloproteinases (such as collagenases) and irreversibly inactivates them by binding to their catalytic zinc cofactor. Known to act on MMP-1, MMP-2, MMP-3, MMP-7, MMP-8, MMP-9, MMP-10, MMP-13, MMP-14, MMP-15, MMP-16 and MMP-19.
• Reactome Pathway:
  Neutrophil degranulation (R-HSA-6798695)
  Activation of Matrix Metalloproteinases (R-HSA-1592389)

Molecular Interaction Atlas (MIA) of This DOT

42 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Atrial fibrillation	DIS15W6U	Definitive	Biomarker	[1]
Pancreatic cancer	DISJC981	Definitive	Biomarker	[2]
Acute myelogenous leukaemia	DISCSPTN	Strong	Genetic Variation	[3]
Adenocarcinoma	DIS3IHTY	Strong	Biomarker	[4]
Adult glioblastoma	DISVP4LU	Strong	Biomarker	[5]
Alzheimer disease	DISF8S70	Strong	Biomarker	[6]
Bladder cancer	DISUHNM0	Strong	Biomarker	[7]
Breast cancer	DIS7DPX1	Strong	Biomarker	[8]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[8]
Cardiomyopathy	DISUPZRG	Strong	Biomarker	[9]
Cervical cancer	DISFSHPF	Strong	Altered Expression	[10]
Cervical carcinoma	DIST4S00	Strong	Altered Expression	[11]
Chronic obstructive pulmonary disease	DISQCIRF	Strong	Altered Expression	[12]
Diabetic kidney disease	DISJMWEY	Strong	Altered Expression	[13]
Eosinophilic esophagitis	DISR8WSB	Strong	Genetic Variation	[14]
Fibrosarcoma	DISWX7MU	Strong	Biomarker	[11]
Gastric cancer	DISXGOUK	Strong	Biomarker	[15]
Glioblastoma multiforme	DISK8246	Strong	Altered Expression	[16]
Glioma	DIS5RPEH	Strong	Biomarker	[17]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[18]
Idiopathic cardiomyopathy	DISUGBZL	Strong	Biomarker	[9]
Myocardial infarction	DIS655KI	Strong	Biomarker	[19]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Biomarker	[20]
Osteoarthritis	DIS05URM	Strong	Biomarker	[21]
Plasma cell myeloma	DIS0DFZ0	Strong	Altered Expression	[22]
Urinary bladder cancer	DISDV4T7	Strong	Biomarker	[7]
Urinary bladder neoplasm	DIS7HACE	Strong	Biomarker	[7]
Breast neoplasm	DISNGJLM	moderate	Altered Expression	[23]
Lung cancer	DISCM4YA	moderate	Altered Expression	[24]
Lung carcinoma	DISTR26C	moderate	Altered Expression	[24]
Squamous cell carcinoma	DISQVIFL	moderate	Biomarker	[4]
Stomach cancer	DISKIJSX	moderate	Biomarker	[15]
Abdominal aortic aneurysm	DISD06OF	Disputed	Altered Expression	[25]
Bone osteosarcoma	DIST1004	Limited	Biomarker	[26]
Calcinosis	DISQP4OR	Limited	Biomarker	[27]
Endometriosis	DISX1AG8	Limited	Genetic Variation	[28]
Familial tumoral calcinosis	DISYJZKG	Limited	Biomarker	[27]
Melanoma	DIS1RRCY	Limited	Biomarker	[29]
Neuroblastoma	DISVZBI4	Limited	Altered Expression	[30]
Osteosarcoma	DISLQ7E2	Limited	Biomarker	[26]
Pleural disease	DISHT9AE	Limited	Biomarker	[27]
Type-1/2 diabetes	DISIUHAP	Limited	Biomarker	[31]

3 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 Metalloproteinase inhibitor 2 (TIMP2).	[32]
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Metalloproteinase inhibitor 2 (TIMP2).	[39]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Metalloproteinase inhibitor 2 (TIMP2).	[62]

48 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 Metalloproteinase inhibitor 2 (TIMP2).	[33]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Metalloproteinase inhibitor 2 (TIMP2).	[34]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Metalloproteinase inhibitor 2 (TIMP2).	[35]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Metalloproteinase inhibitor 2 (TIMP2).	[36]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Metalloproteinase inhibitor 2 (TIMP2).	[37]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Metalloproteinase inhibitor 2 (TIMP2).	[38]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Metalloproteinase inhibitor 2 (TIMP2).	[40]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Metalloproteinase inhibitor 2 (TIMP2).	[41]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Metalloproteinase inhibitor 2 (TIMP2).	[42]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Metalloproteinase inhibitor 2 (TIMP2).	[43]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Metalloproteinase inhibitor 2 (TIMP2).	[44]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of Metalloproteinase inhibitor 2 (TIMP2).	[45]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of Metalloproteinase inhibitor 2 (TIMP2).	[46]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Metalloproteinase inhibitor 2 (TIMP2).	[47]
Zoledronate	DMIXC7G	Approved	Zoledronate increases the expression of Metalloproteinase inhibitor 2 (TIMP2).	[48]
Selenium	DM25CGV	Approved	Selenium decreases the expression of Metalloproteinase inhibitor 2 (TIMP2).	[49]
Menadione	DMSJDTY	Approved	Menadione affects the expression of Metalloproteinase inhibitor 2 (TIMP2).	[43]
Niclosamide	DMJAGXQ	Approved	Niclosamide increases the expression of Metalloproteinase inhibitor 2 (TIMP2).	[50]
Aspirin	DM672AH	Approved	Aspirin decreases the expression of Metalloproteinase inhibitor 2 (TIMP2).	[51]
Nitric Oxide	DM1RBYG	Approved	Nitric Oxide decreases the expression of Metalloproteinase inhibitor 2 (TIMP2).	[52]
Propofol	DMB4OLE	Approved	Propofol increases the expression of Metalloproteinase inhibitor 2 (TIMP2).	[53]
Tetracaine	DM9J6C2	Approved	Tetracaine increases the expression of Metalloproteinase inhibitor 2 (TIMP2).	[54]
Sulfapyridine	DMIUYFH	Approved	Sulfapyridine increases the expression of Metalloproteinase inhibitor 2 (TIMP2).	[55]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Metalloproteinase inhibitor 2 (TIMP2).	[56]
Curcumin	DMQPH29	Phase 3	Curcumin decreases the expression of Metalloproteinase inhibitor 2 (TIMP2).	[57]
Avastin+/-Tarceva	DMA86FL	Phase 3	Avastin+/-Tarceva increases the expression of Metalloproteinase inhibitor 2 (TIMP2).	[58]
Genistein	DM0JETC	Phase 2/3	Genistein decreases the expression of Metalloproteinase inhibitor 2 (TIMP2).	[59]
Thymoquinone	DMVDTR2	Phase 2/3	Thymoquinone increases the expression of Metalloproteinase inhibitor 2 (TIMP2).	[60]
phorbol 12-myristate 13-acetate	DMJWD62	Phase 2	phorbol 12-myristate 13-acetate increases the expression of Metalloproteinase inhibitor 2 (TIMP2).	[61]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Metalloproteinase inhibitor 2 (TIMP2).	[63]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Metalloproteinase inhibitor 2 (TIMP2).	[65]
Scriptaid	DM9JZ21	Preclinical	Scriptaid affects the expression of Metalloproteinase inhibitor 2 (TIMP2).	[66]
Batimastat	DM92VRP	Preclinical	Batimastat decreases the activity of Metalloproteinase inhibitor 2 (TIMP2).	[67]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Metalloproteinase inhibitor 2 (TIMP2).	[68]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Metalloproteinase inhibitor 2 (TIMP2).	[69]
Coumarin	DM0N8ZM	Investigative	Coumarin increases the expression of Metalloproteinase inhibitor 2 (TIMP2).	[70]
Coumestrol	DM40TBU	Investigative	Coumestrol decreases the expression of Metalloproteinase inhibitor 2 (TIMP2).	[38]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane increases the expression of Metalloproteinase inhibitor 2 (TIMP2).	[71]
Deguelin	DMXT7WG	Investigative	Deguelin increases the expression of Metalloproteinase inhibitor 2 (TIMP2).	[72]
3R14S-OCHRATOXIN A	DM2KEW6	Investigative	3R14S-OCHRATOXIN A increases the expression of Metalloproteinase inhibitor 2 (TIMP2).	[73]
methyl p-hydroxybenzoate	DMO58UW	Investigative	methyl p-hydroxybenzoate decreases the activity of Metalloproteinase inhibitor 2 (TIMP2).	[74]
D-glucose	DMMG2TO	Investigative	D-glucose increases the expression of Metalloproteinase inhibitor 2 (TIMP2).	[75]
Phencyclidine	DMQBEYX	Investigative	Phencyclidine increases the expression of Metalloproteinase inhibitor 2 (TIMP2).	[76]
NORCANTHARIDIN	DM9B6Y1	Investigative	NORCANTHARIDIN increases the expression of Metalloproteinase inhibitor 2 (TIMP2).	[77]
Isoarnebin 4	DM0B7NO	Investigative	Isoarnebin 4 increases the expression of Metalloproteinase inhibitor 2 (TIMP2).	[78]
DEMETHOXYCURCUMIN	DMO5UGV	Investigative	DEMETHOXYCURCUMIN decreases the expression of Metalloproteinase inhibitor 2 (TIMP2).	[79]
Plumbagin	DM9BS50	Investigative	Plumbagin increases the expression of Metalloproteinase inhibitor 2 (TIMP2).	[80]
Asacolitin	DM3WVPJ	Investigative	Asacolitin increases the expression of Metalloproteinase inhibitor 2 (TIMP2).	[55]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Metastat	DMTQ4PN	Phase 1	Metastat decreases the secretion of Metalloproteinase inhibitor 2 (TIMP2).	[64]

References

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