Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTR9XHZ)

• DTT Name: Transforming growth factor beta 1 (TGFB1)
• Synonyms: Transforming growth factor beta-1 proprotein; Transforming growth factor beta-1; TGFB; TGF-beta1; TGF-beta 1
• Gene Name: TGFB1
• DTT Type: Successful target; [1]
• BioChemical Class: Growth factor
• UniProt ID: TGFB1_HUMAN
• TTD ID: T97257
• Sequence:
  MPPSGLRLLLLLLPLLWLLVLTPGRPAAGLSTCKTIDMELVKRKRIEAIRGQILSKLRLA
  SPPSQGEVPPGPLPEAVLALYNSTRDRVAGESAEPEPEPEADYYAKEVTRVLMVETHNEI
  YDKFKQSTHSIYMFFNTSELREAVPEPVLLSRAELRLLRLKLKVEQHVELYQKYSNNSWR
  YLSNRLLAPSDSPEWLSFDVTGVVRQWLSRGGEIEGFRLSAHCSCDSRDNTLQVDINGFT
  TGRRGDLATIHGMNRPFLLLMATPLERAQHLQSSRHRRALDTNYCFSSTEKNCCVRQLYI
  DFRKDLGWKWIHEPKGYHANFCLGPCPYIWSLDTQYSKVLALYNQHNPGASAAPCCVPQA
  LEPLPIVYYVGRKPKVEQLSNMIVRSCKCS
• Function: Transforming growth factor beta-1 proprotein: Precursor of the Latency-associated peptide (LAP) and Transforming growth factor beta-1 (TGF-beta-1) chains, which constitute the regulatory and active subunit of TGF-beta-1, respectively.
• KEGG Pathway:
  MAPK signaling pathway (hsa04010)
  Cytokine-cytokine receptor interaction (hsa04060)
  FoxO signaling pathway (hsa04068)
  Cell cycle (hsa04110)
  Endocytosis (hsa04144)
  TGF-beta signaling pathway (hsa04350)
  Osteoclast differentiation (hsa04380)
  Hippo signaling pathway (hsa04390)
  Intestinal immune network for IgA production (hsa04672)
  Non-alcoholic fatty liver disease (NAFLD) (hsa04932)
  Leishmaniasis (hsa05140)
  Chagas disease (American trypanosomiasis) (hsa05142)
  Malaria (hsa05144)
  Toxoplasmosis (hsa05145)
  Amoebiasis (hsa05146)
  Tuberculosis (hsa05152)
  Hepatitis B (hsa05161)
  HTLV-I infection (hsa05166)
  Pathways in cancer (hsa05200)
  Proteoglycans in cancer (hsa05205)
  Colorectal cancer (hsa05210)
  Renal cell carcinoma (hsa05211)
  Pancreatic cancer (hsa05212)
  Chronic myeloid leukemia (hsa05220)
  Inflammatory bowel disease (IBD) (hsa05321)
  Rheumatoid arthritis (hsa05323)
  Hypertrophic cardiomyopathy (HCM) (hsa05410)
  Dilated cardiomyopathy (hsa05414)
• Reactome Pathway:
  Molecules associated with elastic fibres (R-HSA-2129379)
  TGF-beta receptor signaling activates SMADs (R-HSA-2173789)
  TGF-beta receptor signaling in EMT (epithelial to mesenchymal transition) (R-HSA-2173791)
  Syndecan interactions (R-HSA-3000170)
  ECM proteoglycans (R-HSA-3000178)
  SMAD2/3 Phosphorylation Motif Mutants in Cancer (R-HSA-3304356)
  SMAD2/3 MH2 Domain Mutants in Cancer (R-HSA-3315487)
  TGFBR2 Kinase Domain Mutants in Cancer (R-HSA-3645790)
  TGFBR1 KD Mutants in Cancer (R-HSA-3656532)
  TGFBR1 LBD Mutants in Cancer (R-HSA-3656535)
  Transcriptional regulation of white adipocyte differentiation (R-HSA-381340)
  Platelet degranulation (R-HSA-114608)

Molecular Interaction Atlas (MIA) of This DTT

1 Approved Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Pirfenidone	DM6VZFQ	Idiopathic pulmonary fibrosis	CB03.4	Approved	[1]

7 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
A435	DMJCL7X	Aggressive cancer	2A00-2F9Z	IND submitted	[2]
TG-C	DMLCXPD	Arthritis	FA20	Phase 3	[3]
LY2157299	DMP8HW1	Arteriosclerosis	BD40	Phase 2/3	[4]
Disitertide	DM2QBDS	Macular degeneration	9B78.3	Phase 2	[5]
ABBV-151	DMIQXDJ	Solid tumour/cancer	2A00-2F9Z	Phase 1	[6]
ACE-1334	DMF1OUP	Systemic sclerosis	4A42	Phase 1	[7]
SRK-181	DM0EWMT	Solid tumour/cancer	2A00-2F9Z	Phase 1	[8]

1 Discontinued Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Mannose phosphate	DM1LM7D	Lesion	8A00-8C12	Discontinued in Phase 2	[9]

1 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
ART-144	DMEVT4I	Osteoarthritis	FA00-FA05	Investigative	[10]

Molecular Expression Atlas (MEA) of This DTT

Disease Name	ICD 11	Studied Tissue	p-value	Fold-Change	Z-score
Rheumatoid arthritis	FA20	Synovial tissue	5.95E-09	1.68	7.81
Osteoarthritis	FA20	Synovial tissue	6.16E-01	-0.14	-0.11

References

• [1] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
• [2] Clinical pipeline report, company report or official report of Klus Pharma
• [3] Clinical pipeline report, company report or official report of Tissue Gene, Inc.
• [4] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [5] Perspectives of TGF-beta inhibition in pancreatic and hepatocellular carcinomas. Oncotarget. 2014 January; 5(1): 78-94.
• [6] Clinical pipeline report, company report or official report of AbbVie.
• [7] Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2023. Adis Insight
• [8] Clinical pipeline report, company report or official report of Scholar Rock.
• [9] The mannose-6-phosphate analogue, PXS64, inhibits fibrosis via TGF-beta1 pathway in human lung fibroblasts. Immunol Lett. 2015 Jun;165(2):90-101.
• [10] Pharmaceutical products of TORREYA partners. December 2011.