Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTDGQAD1)

• DOT Name: Metalloproteinase inhibitor 3 (TIMP3)
• Synonyms: Protein MIG-5; Tissue inhibitor of metalloproteinases 3; TIMP-3
• Gene Name: TIMP3
• Related Disease:
  Psoriasis
  Retinopathy
  Sorsby fundus dystrophy
  Acute myelogenous leukaemia
  Adenocarcinoma
  Advanced cancer
  Asthma
  Bladder cancer
  Blindness
  Bone osteosarcoma
  Breast cancer
  Breast carcinoma
  Breast neoplasm
  Colitis
  Colorectal carcinoma
  Diabetic kidney disease
  Esophageal squamous cell carcinoma
  Gastric cancer
  Head-neck squamous cell carcinoma
  Hepatocellular carcinoma
  Meningioma
  Metastatic malignant neoplasm
  Myocardial infarction
  Non-small-cell lung cancer
  Osteoarthritis
  Osteosarcoma
  Periodontitis
  Rheumatoid arthritis
  Squamous cell carcinoma
  Thyroid gland papillary carcinoma
  Urinary bladder cancer
  Urinary bladder neoplasm
  Gastric neoplasm
  Lung cancer
  Lung carcinoma
  Stomach cancer
  Melanoma
  Arteriosclerosis
  Atherosclerosis
  Bladder disease
  Carcinoma
  Clear cell renal carcinoma
  Glioblastoma multiforme
  Hereditary diffuse gastric adenocarcinoma
  Renal cell carcinoma
  Schistosomiasis
  Type-1/2 diabetes
• UniProt ID: TIMP3_HUMAN
• PDB ID: 3CKI
• Pfam ID: PF00965
• Sequence:
  MTPWLGLIVLLGSWSLGDWGAEACTCSPSHPQDAFCNSDIVIRAKVVGKKLVKEGPFGTL
  VYTIKQMKMYRGFTKMPHVQYIHTEASESLCGLKLEVNKYQYLLTGRVYDGKMYTGLCNF
  VERWDQLTLSQRKGLNYRYHLGCNCKIKSCYYLPCFVTSKNECLWTDMLSNFGYPGYQSK
  HYACIRQKGGYCSWYRGWAPPDKSIINATDP
• Function: Complexes with metalloproteinases (such as collagenases) and irreversibly inactivates them by binding to their catalytic zinc cofactor. May form part of a tissue-specific acute response to remodeling stimuli. Known to act on MMP-1, MMP-2, MMP-3, MMP-7, MMP-9, MMP-13, MMP-14 and MMP-15.
• KEGG Pathway:
  Proteoglycans in cancer (hsa05205)
  MicroR.s in cancer (hsa05206)
• Reactome Pathway: Platelet degranulation (R-HSA-114608)

Molecular Interaction Atlas (MIA) of This DOT

47 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Psoriasis	DIS59VMN	Definitive	Biomarker	[1]
Retinopathy	DISB4B0F	Definitive	Genetic Variation	[2]
Sorsby fundus dystrophy	DISFVBJE	Definitive	Autosomal dominant	[3]
Acute myelogenous leukaemia	DISCSPTN	Strong	Biomarker	[4]
Adenocarcinoma	DIS3IHTY	Strong	Biomarker	[5]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[6]
Asthma	DISW9QNS	Strong	Biomarker	[7]
Bladder cancer	DISUHNM0	Strong	Genetic Variation	[8]
Blindness	DISTIM10	Strong	Altered Expression	[9]
Bone osteosarcoma	DIST1004	Strong	Altered Expression	[10]
Breast cancer	DIS7DPX1	Strong	Posttranslational Modification	[11]
Breast carcinoma	DIS2UE88	Strong	Posttranslational Modification	[11]
Breast neoplasm	DISNGJLM	Strong	Genetic Variation	[12]
Colitis	DISAF7DD	Strong	Biomarker	[13]
Colorectal carcinoma	DIS5PYL0	Strong	Genetic Variation	[6]
Diabetic kidney disease	DISJMWEY	Strong	Altered Expression	[14]
Esophageal squamous cell carcinoma	DIS5N2GV	Strong	Biomarker	[15]
Gastric cancer	DISXGOUK	Strong	Posttranslational Modification	[16]
Head-neck squamous cell carcinoma	DISF7P24	Strong	Genetic Variation	[17]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[18]
Meningioma	DISPT4TG	Strong	Biomarker	[19]
Metastatic malignant neoplasm	DIS86UK6	Strong	Biomarker	[20]
Myocardial infarction	DIS655KI	Strong	Biomarker	[21]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Altered Expression	[22]
Osteoarthritis	DIS05URM	Strong	Altered Expression	[23]
Osteosarcoma	DISLQ7E2	Strong	Altered Expression	[10]
Periodontitis	DISI9JOI	Strong	Altered Expression	[24]
Rheumatoid arthritis	DISTSB4J	Strong	Biomarker	[25]
Squamous cell carcinoma	DISQVIFL	Strong	Posttranslational Modification	[26]
Thyroid gland papillary carcinoma	DIS48YMM	Strong	Altered Expression	[27]
Urinary bladder cancer	DISDV4T7	Strong	Genetic Variation	[8]
Urinary bladder neoplasm	DIS7HACE	Strong	Genetic Variation	[8]
Gastric neoplasm	DISOKN4Y	moderate	Biomarker	[28]
Lung cancer	DISCM4YA	moderate	Biomarker	[29]
Lung carcinoma	DISTR26C	moderate	Biomarker	[29]
Stomach cancer	DISKIJSX	moderate	Posttranslational Modification	[16]
Melanoma	DIS1RRCY	Disputed	Altered Expression	[30]
Arteriosclerosis	DISK5QGC	Limited	Biomarker	[31]
Atherosclerosis	DISMN9J3	Limited	Biomarker	[31]
Bladder disease	DISTVIQI	Limited	Biomarker	[32]
Carcinoma	DISH9F1N	Limited	Altered Expression	[33]
Clear cell renal carcinoma	DISBXRFJ	Limited	Biomarker	[34]
Glioblastoma multiforme	DISK8246	Limited	Biomarker	[35]
Hereditary diffuse gastric adenocarcinoma	DISUIBYS	Limited	Biomarker	[36]
Renal cell carcinoma	DISQZ2X8	Limited	Biomarker	[34]
Schistosomiasis	DIS6PD44	Limited	Biomarker	[32]
Type-1/2 diabetes	DISIUHAP	Limited	Altered Expression	[37]

This DOT Affected the Drug Response of 2 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Cytarabine	DMZD5QR	Approved	Metalloproteinase inhibitor 3 (TIMP3) decreases the response to substance of Cytarabine.	[79]
Floxuridine	DM04LR2	Approved	Metalloproteinase inhibitor 3 (TIMP3) decreases the response to substance of Floxuridine.	[79]

2 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 Metalloproteinase inhibitor 3 (TIMP3).	[38]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the methylation of Metalloproteinase inhibitor 3 (TIMP3).	[71]

41 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 3 (TIMP3).	[39]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Metalloproteinase inhibitor 3 (TIMP3).	[40]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Metalloproteinase inhibitor 3 (TIMP3).	[41]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Metalloproteinase inhibitor 3 (TIMP3).	[42]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Metalloproteinase inhibitor 3 (TIMP3).	[43]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Metalloproteinase inhibitor 3 (TIMP3).	[44]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Metalloproteinase inhibitor 3 (TIMP3).	[45]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Metalloproteinase inhibitor 3 (TIMP3).	[46]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of Metalloproteinase inhibitor 3 (TIMP3).	[47]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of Metalloproteinase inhibitor 3 (TIMP3).	[48]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of Metalloproteinase inhibitor 3 (TIMP3).	[49]
Methotrexate	DM2TEOL	Approved	Methotrexate increases the expression of Metalloproteinase inhibitor 3 (TIMP3).	[50]
Decitabine	DMQL8XJ	Approved	Decitabine increases the expression of Metalloproteinase inhibitor 3 (TIMP3).	[36]
Selenium	DM25CGV	Approved	Selenium decreases the expression of Metalloproteinase inhibitor 3 (TIMP3).	[52]
Progesterone	DMUY35B	Approved	Progesterone decreases the expression of Metalloproteinase inhibitor 3 (TIMP3).	[49]
Fluorouracil	DMUM7HZ	Approved	Fluorouracil increases the expression of Metalloproteinase inhibitor 3 (TIMP3).	[53]
Isotretinoin	DM4QTBN	Approved	Isotretinoin increases the expression of Metalloproteinase inhibitor 3 (TIMP3).	[54]
Testosterone enanthate	DMB6871	Approved	Testosterone enanthate affects the expression of Metalloproteinase inhibitor 3 (TIMP3).	[55]
Nicotine	DMWX5CO	Approved	Nicotine affects the expression of Metalloproteinase inhibitor 3 (TIMP3).	[56]
Indomethacin	DMSC4A7	Approved	Indomethacin increases the expression of Metalloproteinase inhibitor 3 (TIMP3).	[53]
Capsaicin	DMGMF6V	Approved	Capsaicin increases the expression of Metalloproteinase inhibitor 3 (TIMP3).	[57]
Rofecoxib	DM3P5DA	Approved	Rofecoxib decreases the expression of Metalloproteinase inhibitor 3 (TIMP3).	[58]
Isoproterenol	DMK7MEY	Approved	Isoproterenol increases the expression of Metalloproteinase inhibitor 3 (TIMP3).	[59]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Metalloproteinase inhibitor 3 (TIMP3).	[61]
Genistein	DM0JETC	Phase 2/3	Genistein decreases the expression of Metalloproteinase inhibitor 3 (TIMP3).	[62]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol increases the expression of Metalloproteinase inhibitor 3 (TIMP3).	[63]
Belinostat	DM6OC53	Phase 2	Belinostat decreases the expression of Metalloproteinase inhibitor 3 (TIMP3).	[48]
DNCB	DMDTVYC	Phase 2	DNCB increases the expression of Metalloproteinase inhibitor 3 (TIMP3).	[64]
Tanespimycin	DMNLQHK	Phase 2	Tanespimycin increases the expression of Metalloproteinase inhibitor 3 (TIMP3).	[65]
ANW-32821	DMMJOZD	Phase 2	ANW-32821 increases the expression of Metalloproteinase inhibitor 3 (TIMP3).	[66]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Metalloproteinase inhibitor 3 (TIMP3).	[67]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Metalloproteinase inhibitor 3 (TIMP3).	[68]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide increases the expression of Metalloproteinase inhibitor 3 (TIMP3).	[69]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN increases the expression of Metalloproteinase inhibitor 3 (TIMP3).	[70]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Metalloproteinase inhibitor 3 (TIMP3).	[72]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Metalloproteinase inhibitor 3 (TIMP3).	[73]
Coumestrol	DM40TBU	Investigative	Coumestrol decreases the expression of Metalloproteinase inhibitor 3 (TIMP3).	[74]
Glyphosate	DM0AFY7	Investigative	Glyphosate increases the expression of Metalloproteinase inhibitor 3 (TIMP3).	[75]
Rapamycin Immunosuppressant Drug	DM678IB	Investigative	Rapamycin Immunosuppressant Drug decreases the expression of Metalloproteinase inhibitor 3 (TIMP3).	[76]
acrolein	DMAMCSR	Investigative	acrolein decreases the expression of Metalloproteinase inhibitor 3 (TIMP3).	[77]
4-[1-(4-hydroxyphenyl)-2-phenylbut-1-enyl]phenol	DMTMLXU	Investigative	4-[1-(4-hydroxyphenyl)-2-phenylbut-1-enyl]phenol decreases the expression of Metalloproteinase inhibitor 3 (TIMP3).	[78]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Pentosan polysulfate	DM2HRKE	Approved	Pentosan polysulfate increases the secretion of Metalloproteinase inhibitor 3 (TIMP3).	[60]

References

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