Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTC0TXEP)

• DOT Name: Transforming growth factor beta-2 proprotein (TGFB2)
• Synonyms: Cetermin; Glioblastoma-derived T-cell suppressor factor; G-TSF
• Gene Name: TGFB2
• Related Disease:
  Familial thoracic aortic aneurysm and aortic dissection
  Loeys-Dietz syndrome 4
• UniProt ID: TGFB2_HUMAN
• PDB ID: 1TFG; 2TGI; 4KXZ; 5TX4; 5TY4; 6I9J; 6XM2; 7RCO; 8DC0; 8FXS; 8FXV
• Pfam ID: PF00019 ; PF00688
• Sequence:
  MHYCVLSAFLILHLVTVALSLSTCSTLDMDQFMRKRIEAIRGQILSKLKLTSPPEDYPEP
  EEVPPEVISIYNSTRDLLQEKASRRAAACERERSDEEYYAKEVYKIDMPPFFPSENAIPP
  TFYRPYFRIVRFDVSAMEKNASNLVKAEFRVFRLQNPKARVPEQRIELYQILKSKDLTSP
  TQRYIDSKVVKTRAEGEWLSFDVTDAVHEWLHHKDRNLGFKISLHCPCCTFVPSNNYIIP
  NKSEELEARFAGIDGTSTYTSGDQKTIKSTRKKNSGKTPHLLLMLLPSYRLESQQTNRRK
  KRALDAAYCFRNVQDNCCLRPLYIDFKRDLGWKWIHEPKGYNANFCAGACPYLWSSDTQH
  SRVLSLYNTINPEASASPCCVSQDLEPLTILYYIGKTPKIEQLSNMIVKSCKCS
• Function: [Transforming growth factor beta-2 proprotein]: Precursor of the Latency-associated peptide (LAP) and Transforming growth factor beta-2 (TGF-beta-2) chains, which constitute the regulatory and active subunit of TGF-beta-2, respectively; [Latency-associated peptide]: Required to maintain the Transforming growth factor beta-2 (TGF-beta-2) chain in a latent state during storage in extracellular matrix. Associates non-covalently with TGF-beta-2 and regulates its activation via interaction with 'milieu molecules', such as LTBP1 and LRRC32/GARP, that control activation of TGF-beta-2; [Transforming growth factor beta-2]: Multifunctional protein that regulates various processes such as angiogenesis and heart development. Activation into mature form follows different steps: following cleavage of the proprotein in the Golgi apparatus, Latency-associated peptide (LAP) and Transforming growth factor beta-2 (TGF-beta-2) chains remain non-covalently linked rendering TGF-beta-2 inactive during storage in extracellular matrix. At the same time, LAP chain interacts with 'milieu molecules', such as LTBP1 and LRRC32/GARP, that control activation of TGF-beta-2 and maintain it in a latent state during storage in extracellular milieus. Once activated following release of LAP, TGF-beta-2 acts by binding to TGF-beta receptors (TGFBR1 and TGFBR2), which transduce signal.
• KEGG Pathway:
  MAPK sig.ling pathway (hsa04010)
  Cytokine-cytokine receptor interaction (hsa04060)
  FoxO sig.ling pathway (hsa04068)
  Cell cycle (hsa04110)
  Cellular senescence (hsa04218)
  TGF-beta sig.ling pathway (hsa04350)
  Osteoclast differentiation (hsa04380)
  Hippo sig.ling pathway (hsa04390)
  AGE-RAGE sig.ling pathway in diabetic complications (hsa04933)
  Leishmaniasis (hsa05140)
  Chagas disease (hsa05142)
  Malaria (hsa05144)
  Toxoplasmosis (hsa05145)
  Amoebiasis (hsa05146)
  Tuberculosis (hsa05152)
  Hepatitis B (hsa05161)
  Human T-cell leukemia virus 1 infection (hsa05166)
  Pathways in cancer (hsa05200)
  Proteoglycans in cancer (hsa05205)
  MicroR.s in cancer (hsa05206)
  Colorectal cancer (hsa05210)
  Re.l cell carcinoma (hsa05211)
  Pancreatic cancer (hsa05212)
  Chronic myeloid leukemia (hsa05220)
  Hepatocellular carcinoma (hsa05225)
  Gastric cancer (hsa05226)
  Inflammatory bowel disease (hsa05321)
  Rheumatoid arthritis (hsa05323)
  Hypertrophic cardiomyopathy (hsa05410)
  Dilated cardiomyopathy (hsa05414)
  Diabetic cardiomyopathy (hsa05415)
• Reactome Pathway:
  Molecules associated with elastic fibres (R-HSA-2129379)
  TGF-beta receptor signaling activates SMADs (R-HSA-2173789)
  ECM proteoglycans (R-HSA-3000178)
  Platelet degranulation (R-HSA-114608)

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Familial thoracic aortic aneurysm and aortic dissection	DIS069FB	Definitive	Autosomal dominant	[1]
Loeys-Dietz syndrome 4	DISG09TJ	Definitive	Autosomal dominant	[2]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Fluorouracil	DMUM7HZ	Approved	Transforming growth factor beta-2 proprotein (TGFB2) affects the response to substance of Fluorouracil.	[38]

4 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 Transforming growth factor beta-2 proprotein (TGFB2).	[3]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Transforming growth factor beta-2 proprotein (TGFB2).	[28]
TAK-243	DM4GKV2	Phase 1	TAK-243 increases the sumoylation of Transforming growth factor beta-2 proprotein (TGFB2).	[30]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Transforming growth factor beta-2 proprotein (TGFB2).	[34]

32 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 Transforming growth factor beta-2 proprotein (TGFB2).	[4]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Transforming growth factor beta-2 proprotein (TGFB2).	[5]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Transforming growth factor beta-2 proprotein (TGFB2).	[6]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Transforming growth factor beta-2 proprotein (TGFB2).	[7]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Transforming growth factor beta-2 proprotein (TGFB2).	[8]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide increases the expression of Transforming growth factor beta-2 proprotein (TGFB2).	[9]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Transforming growth factor beta-2 proprotein (TGFB2).	[10]
Testosterone	DM7HUNW	Approved	Testosterone increases the expression of Transforming growth factor beta-2 proprotein (TGFB2).	[11]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of Transforming growth factor beta-2 proprotein (TGFB2).	[12]
Zoledronate	DMIXC7G	Approved	Zoledronate increases the expression of Transforming growth factor beta-2 proprotein (TGFB2).	[13]
Dexamethasone	DMMWZET	Approved	Dexamethasone decreases the expression of Transforming growth factor beta-2 proprotein (TGFB2).	[14]
Diclofenac	DMPIHLS	Approved	Diclofenac decreases the expression of Transforming growth factor beta-2 proprotein (TGFB2).	[16]
Dasatinib	DMJV2EK	Approved	Dasatinib increases the expression of Transforming growth factor beta-2 proprotein (TGFB2).	[17]
Ethinyl estradiol	DMODJ40	Approved	Ethinyl estradiol decreases the expression of Transforming growth factor beta-2 proprotein (TGFB2).	[18]
Gemcitabine	DMSE3I7	Approved	Gemcitabine increases the expression of Transforming growth factor beta-2 proprotein (TGFB2).	[19]
Obeticholic acid	DM3Q1SM	Approved	Obeticholic acid decreases the expression of Transforming growth factor beta-2 proprotein (TGFB2).	[20]
Acocantherin	DM7JT24	Approved	Acocantherin decreases the expression of Transforming growth factor beta-2 proprotein (TGFB2).	[21]
Adenosine	DMM2NSK	Approved	Adenosine increases the expression of Transforming growth factor beta-2 proprotein (TGFB2).	[22]
Sodium chloride	DMM3950	Approved	Sodium chloride increases the expression of Transforming growth factor beta-2 proprotein (TGFB2).	[23]
Dihydrotestosterone	DM3S8XC	Phase 4	Dihydrotestosterone increases the expression of Transforming growth factor beta-2 proprotein (TGFB2).	[24]
Resveratrol	DM3RWXL	Phase 3	Resveratrol decreases the expression of Transforming growth factor beta-2 proprotein (TGFB2).	[25]
Genistein	DM0JETC	Phase 2/3	Genistein decreases the expression of Transforming growth factor beta-2 proprotein (TGFB2).	[8]
Belinostat	DM6OC53	Phase 2	Belinostat increases the expression of Transforming growth factor beta-2 proprotein (TGFB2).	[27]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Transforming growth factor beta-2 proprotein (TGFB2).	[29]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Transforming growth factor beta-2 proprotein (TGFB2).	[31]
Geldanamycin	DMS7TC5	Discontinued in Phase 2	Geldanamycin increases the expression of Transforming growth factor beta-2 proprotein (TGFB2).	[32]
Torcetrapib	DMDHYM7	Discontinued in Phase 2	Torcetrapib increases the expression of Transforming growth factor beta-2 proprotein (TGFB2).	[33]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Transforming growth factor beta-2 proprotein (TGFB2).	[35]
Coumestrol	DM40TBU	Investigative	Coumestrol decreases the expression of Transforming growth factor beta-2 proprotein (TGFB2).	[36]
3R14S-OCHRATOXIN A	DM2KEW6	Investigative	3R14S-OCHRATOXIN A increases the expression of Transforming growth factor beta-2 proprotein (TGFB2).	[37]
Paraquat	DMR8O3X	Investigative	Paraquat affects the expression of Transforming growth factor beta-2 proprotein (TGFB2).	[12]
Cordycepin	DM72Y01	Investigative	Cordycepin increases the expression of Transforming growth factor beta-2 proprotein (TGFB2).	[22]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Troglitazone	DM3VFPD	Approved	Troglitazone decreases the response to substance of Transforming growth factor beta-2 proprotein (TGFB2).	[15]
Tamibarotene	DM3G74J	Phase 3	Tamibarotene increases the secretion of Transforming growth factor beta-2 proprotein (TGFB2).	[26]

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