Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TT4V2JM)

• DTT Name: Hepatocyte growth factor (HGF)
• Synonyms: Scatter factor; SF; Hepatopoietin-A; Hepatopoeitin A; HPTA
• Gene Name: HGF
• DTT Type: Clinical trial target; [1]
• BioChemical Class: Peptidase
• UniProt ID: HGF_HUMAN
• TTD ID: T83797
• Sequence:
  MWVTKLLPALLLQHVLLHLLLLPIAIPYAEGQRKRRNTIHEFKKSAKTTLIKIDPALKIK
  TKKVNTADQCANRCTRNKGLPFTCKAFVFDKARKQCLWFPFNSMSSGVKKEFGHEFDLYE
  NKDYIRNCIIGKGRSYKGTVSITKSGIKCQPWSSMIPHEHSFLPSSYRGKDLQENYCRNP
  RGEEGGPWCFTSNPEVRYEVCDIPQCSEVECMTCNGESYRGLMDHTESGKICQRWDHQTP
  HRHKFLPERYPDKGFDDNYCRNPDGQPRPWCYTLDPHTRWEYCAIKTCADNTMNDTDVPL
  ETTECIQGQGEGYRGTVNTIWNGIPCQRWDSQYPHEHDMTPENFKCKDLRENYCRNPDGS
  ESPWCFTTDPNIRVGYCSQIPNCDMSHGQDCYRGNGKNYMGNLSQTRSGLTCSMWDKNME
  DLHRHIFWEPDASKLNENYCRNPDDDAHGPWCYTGNPLIPWDYCPISRCEGDTTPTIVNL
  DHPVISCAKTKQLRVVNGIPTRTNIGWMVSLRYRNKHICGGSLIKESWVLTARQCFPSRD
  LKDYEAWLGIHDVHGRGDEKCKQVLNVSQLVYGPEGSDLVLMKLARPAVLDDFVSTIDLP
  NYGCTIPEKTSCSVYGWGYTGLINYDGLLRVAHLYIMGNEKCSQHHRGKVTLNESEICAG
  AEKIGSGPCEGDYGGPLVCEQHKMRMVLGVIVPGRGCAIPNRPGIFVRVAYYAKWIHKII
  LTYKVPQS
• Function: Activating ligand for the receptor tyrosine kinase MET by binding to it and promoting its dimerization. Potent mitogen for mature parenchymal hepatocyte cells, seems to be a hepatotrophic factor, and acts as a growth factor for a broad spectrum of tissues and cell types.
• KEGG Pathway:
  Ras signaling pathway (hsa04014)
  Rap1 signaling pathway (hsa04015)
  Cytokine-cytokine receptor interaction (hsa04060)
  PI3K-Akt signaling pathway (hsa04151)
  Focal adhesion (hsa04510)
  Malaria (hsa05144)
  Pathways in cancer (hsa05200)
  Proteoglycans in cancer (hsa05205)
  Renal cell carcinoma (hsa05211)
  Melanoma (hsa05218)
• Reactome Pathway:
  Interleukin-7 signaling (R-HSA-1266695)
  Platelet degranulation (R-HSA-114608)

Molecular Interaction Atlas (MIA) of This DTT

8 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
ANG-3777	DMGP8WX	Delayed graft function	4B24.0	Phase 3	[2]
Donaperminogene seltoplasmid	DMH8IT5	Diabetic foot ulcer	BD54	Phase 3	[3]
VM-202	DMSW80U	Angina pectoris	BA40	Phase 3	[1]
Collategene	DM27H0P	Peripheral Ischemic Ulcers	BD41	Phase 2	[4]
Ficlatuzumab	DMG65WH	Multiple myeloma	2A83	Phase 2	[5]
MP0250	DMR3VCY	Non-small-cell lung cancer	2C25.Y	Phase 1/2	[5]
ABI-011	DM1KD7U	Lymphoma	2A80-2A86	Phase 1	[5]
TAK-701	DML3M0O	Advanced malignancy	2A00-2F9Z	Phase 1	[6]

1 Discontinued Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Rilotumumab	DMD8ZSW	Grade IV malignant glioma	2A00.0	Discontinued in Phase 2	[7]

2 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
N,O6-Disulfo-Glucosamine	DMYCV7U	Discovery agent	N.A.	Investigative	[8]
O2-Sulfo-Glucuronic Acid	DME78MS	Discovery agent	N.A.	Investigative	[8]

Molecular Expression Atlas (MEA) of This DTT

Disease Name	ICD 11	Studied Tissue	p-value	Fold-Change	Z-score
Glioma	2C82	Brainstem tissue	4.90E-01	0.13	2.73
Glioma	2C82	White matter	1.98E-07	1.58	2.92

References

• [1] Therapeutic angiogenesis using naked DNA expressing two isoforms of the hepatocyte growth factor in a porcine acute myocardial infarction model. Eur J Cardiothorac Surg. 2008 Oct;34(4):857-63.
• [2] Hepatocyte Growth Factor Mimetic ANG-3777 for Cardiac Surgery-Associated Acute Kidney Injury. Kidney Int Rep. 2020 Sep 25;5(12):2325-2332.
• [3] Clinical pipeline report, company report or official report of ViroMed.
• [4] Randomized, double-blind, placebo-controlled clinical trial of hepatocyte growth factor plasmid for critical limb ischemia. Gene Ther. 2010 Sep;17(9):1152-61.
• [5] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [6] Targeting MET in cancer: rationale and progress.Nat Rev Cancer.2012 Jan 24;12(2):89-103.
• [7] Clinical pipeline report, company report or official report of Amgen (2009).
• [8] How many drug targets are there Nat Rev Drug Discov. 2006 Dec;5(12):993-6.