Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTMY81X)

• DTT Name: Heparin-binding growth factor 1 (FGF1)
• Synonyms: HBGF-1; Fibroblast growth factor 1; FGFA; FGF-1; Endothelial cell growth factor; ECGF-beta; ECGF; Beta-endothelial cell growth factor; Acidic fibroblast growth factor; AFGF
• Gene Name: FGF1
• DTT Type: Clinical trial target; [1]
• BioChemical Class: Growth factor
• UniProt ID: FGF1_HUMAN
• TTD ID: T18639
• Sequence:
  MAEGEITTFTALTEKFNLPPGNYKKPKLLYCSNGGHFLRILPDGTVDGTRDRSDQHIQLQ
  LSAESVGEVYIKSTETGQYLAMDTDGLLYGSQTPNEECLFLERLEENHYNTYISKKHAEK
  NWFVGLKKNGSCKRGPRTHYGQKAILFLPLPVSSD
• Function: Functions as potent mitogen in vitro. Acts as a ligand for FGFR1 and integrins. Binds to FGFR1 in the presence of heparin leading to FGFR1 dimerization and activation via sequential autophosphorylation on tyrosine residues which act as docking sites for interacting proteins, leading to the activation of several signaling cascades. Binds to integrin ITGAV:ITGB3. Its binding to integrin, subsequent ternary complex formation with integrin and FGFR1, and the recruitment of PTPN11 to the complex are essential for FGF1 signaling. Induces the phosphorylation and activation of FGFR1, FRS2, MAPK3/ERK1, MAPK1/ERK2 and AKT1. Can induce angiogenesis. Plays an important role in the regulation of cell survival, cell division, angiogenesis, cell differentiation and cell migration.
• KEGG Pathway:
  MAPK signaling pathway (hsa04010)
  Ras signaling pathway (hsa04014)
  Rap1 signaling pathway (hsa04015)
  PI3K-Akt signaling pathway (hsa04151)
  Hippo signaling pathway (hsa04390)
  Regulation of actin cytoskeleton (hsa04810)
  Pathways in cancer (hsa05200)
  Melanoma (hsa05218)
• Reactome Pathway:
  PIP3 activates AKT signaling (R-HSA-1257604)
  FGFR4 ligand binding and activation (R-HSA-190322)
  FGFR3c ligand binding and activation (R-HSA-190372)
  FGFR2c ligand binding and activation (R-HSA-190375)
  FGFR2b ligand binding and activation (R-HSA-190377)
  FGFR3 mutant receptor activation (R-HSA-2033514)
  Activated point mutants of FGFR2 (R-HSA-2033519)
  Constitutive Signaling by Aberrant PI3K in Cancer (R-HSA-2219530)
  Phospholipase C-mediated cascade (R-HSA-5654219)
  Phospholipase C-mediated cascade (R-HSA-5654221)
  Phospholipase C-mediated cascade (R-HSA-5654227)
  Phospholipase C-mediated cascade (R-HSA-5654228)
  SHC-mediated cascade (R-HSA-5654688)
  PI-3K cascade (R-HSA-5654689)
  FRS-mediated FGFR1 signaling (R-HSA-5654693)
  PI-3K cascade (R-HSA-5654695)
  SHC-mediated cascade (R-HSA-5654699)
  FRS-mediated FGFR2 signaling (R-HSA-5654700)
  SHC-mediated cascade (R-HSA-5654704)
  FRS-mediated FGFR3 signaling (R-HSA-5654706)
  PI-3K cascade (R-HSA-5654710)
  FRS-mediated FGFR4 signaling (R-HSA-5654712)
  SHC-mediated cascade (R-HSA-5654719)
  PI-3K cascade (R-HSA-5654720)
  Negative regulation of FGFR1 signaling (R-HSA-5654726)
  Negative regulation of FGFR2 signaling (R-HSA-5654727)
  Negative regulation of FGFR3 signaling (R-HSA-5654732)
  Negative regulation of FGFR4 signaling (R-HSA-5654733)
  RAF/MAP kinase cascade (R-HSA-5673001)
  PI3K Cascade (R-HSA-109704)

Molecular Interaction Atlas (MIA) of This DTT

1 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
CVBT-141H	DMYPXQ2	Coronary artery disease	BA80	Phase 2	[1]

1 Discontinued Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Riferminogene pecaplasmid	DMBKN4P	Critical limb ischemia	BD4Y	Discontinued in Phase 3	[2]

6 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
5-AMINO-NAPHTALENE-2-MONOSULFONATE	DMYTUNE	Discovery agent	N.A.	Investigative	[3]
Formic Acid	DMNFZC6	Discovery agent	N.A.	Investigative	[4]
N,O6-Disulfo-Glucosamine	DMYCV7U	Discovery agent	N.A.	Investigative	[4]
Naphthalene Trisulfonate	DML6FI3	Discovery agent	N.A.	Investigative	[4]
O2-Sulfo-Glucuronic Acid	DME78MS	Discovery agent	N.A.	Investigative	[4]
Sucrose Octasulfate	DMET64R	Discovery agent	N.A.	Investigative	[4]

Molecular Expression Atlas (MEA) of This DTT

Disease Name	ICD 11	Studied Tissue	p-value	Fold-Change	Z-score
Coronary artery disease	BA80-BA8Z	Peripheral blood	9.56E-01	-0.02	-0.11

References

• [1] Clinical pipeline report, company report or official report of CVBT.
• [2] Riferminogene pecaplasmide. Am J Cardiovasc Drugs. 2010;10(5):343-6.
• [3] The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42.
• [4] How many drug targets are there Nat Rev Drug Discov. 2006 Dec;5(12):993-6.