Details of the Drug Therapeutic Target (DTT)

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

• DTT Name: Fibroblast growth factor-2 (FGF2)
• Synonyms: bFGF; Heparin-binding growth factor 2; HBGF-2; Fibroblast growth factor 2; FGFB; FGF-2; Basic fibroblast growth factor
• Gene Name: FGF2
• DTT Type: Successful target; [1]
• BioChemical Class: Growth factor
• UniProt ID: FGF2_HUMAN
• TTD ID: T31621
• Sequence:
  MVGVGGGDVEDVTPRPGGCQISGRGARGCNGIPGAAAWEAALPRRRPRRHPSVNPRSRAA
  GSPRTRGRRTEERPSGSRLGDRGRGRALPGGRLGGRGRGRAPERVGGRGRGRGTAAPRAA
  PAARGSRPGPAGTMAAGSITTLPALPEDGGSGAFPPGHFKDPKRLYCKNGGFFLRIHPDG
  RVDGVREKSDPHIKLQLQAEERGVVSIKGVCANRYLAMKEDGRLLASKCVTDECFFFERL
  ESNNYNTYRSRKYTSWYVALKRTGQYKLGSKTGPGQKAILFLPMSAKS
• Function: Acts as a ligand for FGFR1, FGFR2, FGFR3 and FGFR4. Also acts as an integrin ligand which is required for FGF2 signaling. Binds to integrin ITGAV:ITGB3. Plays an important role in the regulation of cell survival, cell division, cell differentiation and cell migration. Functions as a potent mitogen in vitro. Can induce angiogenesis.
• KEGG Pathway:
  MAPK signaling pathway (hsa04010)
  Ras signaling pathway (hsa04014)
  Rap1 signaling pathway (hsa04015)
  PI3K-Akt signaling pathway (hsa04151)
  Signaling pathways regulating pluripotency of stem cells (hsa04550)
  Regulation of actin cytoskeleton (hsa04810)
  Pathways in cancer (hsa05200)
  Proteoglycans in cancer (hsa05205)
  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)
  POU5F1 (OCT4), SOX2, NANOG activate genes related to proliferation (R-HSA-2892247)
  Syndecan interactions (R-HSA-3000170)
  Non-integrin membrane-ECM interactions (R-HSA-3000171)
  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 Approved Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Sucralfate	DMP9HBO	Acne vulgaris	ED80	Approved	[1]

4 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Squalamine	DM3PS2E	Solid tumour/cancer	2A00-2F9Z	Phase 3	[2]
Bemarituzumab	DMWNYIE	Gastric adenocarcinoma	2B72	Phase 2	[3]
DVC1-0101	DMUGBQK	Arteriosclerosis	BD40	Phase 2	[4]
FPA144	DM1EBRK	Bladder cancer	2C94	Phase 1	[5]

2 Discontinued Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
TGP-580	DMYN6G0	Neurodegenerative disorder	8A20-8A23	Discontinued in Phase 2	[6]
RG-8803	DMI0CYV	Diabetic retinopathy	9B71.0	Terminated	[7]

5 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
1,4-Dideoxy-5-Dehydro-O2-Sulfo-Glucuronic Acid	DM4RD2S	Discovery agent	N.A.	Investigative	[8]
1,4-Dideoxy-O2-Sulfo-Glucuronic Acid	DM9KUQZ	Discovery agent	N.A.	Investigative	[8]
2-Sulfhydryl-Ethanol	DMJBO3D	Discovery agent	N.A.	Investigative	[8]
BIBF100	DMUWO6D	Multiple myeloma	2A83	Investigative	[9]
N,O6-Disulfo-Glucosamine	DMYCV7U	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
Coronary artery disease	BA80-BA8Z	Peripheral blood	5.52E-01	-1.67E-03	-0.02
Multiple myeloma	2C82	Bone marrow	6.36E-03	0.05	0.3

References

• [1] Assessment of sucralfate coating by sequential scintigraphic imaging in radiation-induced esophageal lesions. Gastrointest Endosc. 1995 Feb;41(2):109-14.
• [2] Clinical pipeline report, company report or official report of Ohr Pharmaceutical.
• [3] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [4] DVC1-0101 to treat peripheral arterial disease: a Phase I/IIa open-label dose-escalation clinical trial. Mol Ther. 2013 Mar;21(3):707-14.
• [5] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [6] Expression of fibroblast growth factor-2 transcripts in the healing of acetic acid-induced gastric ulcers. APMIS. 1999 Aug;107(8):767-72.
• [7] US patent application no. 2010,0278,784, Methods and compositions for treating skin conditions.
• [8] How many drug targets are there Nat Rev Drug Discov. 2006 Dec;5(12):993-6.
• [9] Emerging therapies for multiple myeloma. Expert Opin Emerg Drugs. 2009 Mar;14(1):99-127.