Target Information

Target General Information

Target ID

T28076 (Former ID: TTDI01961)

Target Name

Fibroblast growth factor-4 (FGF4)

Synonyms

Transforming protein KS3; Heparinbinding growth factor 4; Heparin secretorytransforming protein 1; HST1; HST; HBGF4; Fibroblast growth factor 4; FGF4

Click to Show/Hide

Gene Name

FGF4

Target Type

Successful target

[1]

Disease

[+] 2 Target-related Diseases

Chronic pain [ICD-11: MG30]

Cystitis [ICD-11: GC00]

Function

Plays an important role in the regulation of embryonic development, cell proliferation, and cell differentiation. Required for normal limb and cardiac valve development during embryogenesis.

Click to Show/Hide

BioChemical Class

Heparin-binding growth factors family

UniProt ID

FGF4_HUMAN

Sequence

MSGPGTAAVALLPAVLLALLAPWAGRGGAAAPTAPNGTLEAELERRWESLVALSLARLPV
AAQPKEAAVQSGAGDYLLGIKRLRRLYCNVGIGFHLQALPDGRIGGAHADTRDSLLELSP
VERGVVSIFGVASRFFVAMSSKGKLYGSPFFTDECTFKEILLPNNYNAYESYKYPGMFIA
LSKNGKTKKGNRVSPTMKVTHFLPRL

Click to Show/Hide

3D Structure

Click to Show 3D Structure of This Target

AlphaFold

ADReCS ID

BADD_A02053

Drugs and Modes of Action

Top

Approved Drug(s)

[+] 1 Approved Drugs

Pentosan Polysulfate

Drug Info

Approved

Painful bladder syndrome

[2]

Clinical Trial Drug(s)

[+] 3 Clinical Trial Drugs

Ad5FGF-4

Drug Info

Phase 3

Angina pectoris

[3]

Alferminogene tadenovec

Drug Info

Phase 3

Heart disease

[4]

Generx

Drug Info

Phase 3

Angina pectoris

[5]

Mode of Action

[+] 2 Modes of Action

Modulator

[+] 3 Modulator drugs

Pentosan Polysulfate

Drug Info

[1]

Ad5FGF-4

Drug Info

[6]

Alferminogene tadenovec

Drug Info

[4]

Replacement

[+] 1 Replacement drugs

Generx

Drug Info

[7]

Cell-based Target Expression Variations

Top

Cell-based Target Expression Variations

Cell-based Target Expression Variations Info

Different Human System Profiles of Target	Top
Human Similarity Proteins of target is determined by comparing the sequence similarity of all human proteins with the target based on BLAST. The similarity proteins for a target are defined as the proteins with E-value < 0.005 and outside the protein families of the target. A target that has fewer human similarity proteins outside its family is commonly regarded to possess a greater capacity to avoid undesired interactions and thus increase the possibility of finding successful drugs (Brief Bioinform, 21: 649-662, 2020). Human Pathway Affiliation of target is determined by the life-essential pathways provided on KEGG database. The target-affiliated pathways were defined based on the following two criteria (a) the pathways of the studied target should be life-essential for both healthy individuals and patients, and (b) the studied target should occupy an upstream position in the pathways and therefore had the ability to regulate biological function. Targets involved in a fewer pathways have greater likelihood to be successfully developed, while those associated with more human pathways increase the chance of undesirable interferences with other human processes (Pharmacol Rev, 58: 259-279, 2006). Biological Network Descriptors of target is determined based on a human protein-protein interactions (PPI) network consisting of 9,309 proteins and 52,713 PPIs, which were with a high confidence score of ≥ 0.95 collected from STRING database. The network properties of targets based on protein-protein interactions (PPIs) have been widely adopted for the assessment of target’s druggability. Proteins with high node degree tend to have a high impact on network function through multiple interactions, while proteins with high betweenness centrality are regarded to be central for communication in interaction networks and regulate the flow of signaling information (Front Pharmacol, 9, 1245, 2018; Curr Opin Struct Biol. 44:134-142, 2017). Human Similarity Proteins Human Pathway Affiliation Biological Network Descriptors

Different Human System Profiles of Target

Top

Human Similarity Proteins of target is determined by comparing the sequence similarity of all human proteins with the target based on BLAST. The similarity proteins for a target are defined as the proteins with E-value < 0.005 and outside the protein families of the target.

A target that has fewer human similarity proteins outside its family is commonly regarded to possess a greater capacity to avoid undesired interactions and thus increase the possibility of finding successful drugs (Brief Bioinform, 21: 649-662, 2020).

Human Pathway Affiliation of target is determined by the life-essential pathways provided on KEGG database. The target-affiliated pathways were defined based on the following two criteria (a) the pathways of the studied target should be life-essential for both healthy individuals and patients, and (b) the studied target should occupy an upstream position in the pathways and therefore had the ability to regulate biological function.

Targets involved in a fewer pathways have greater likelihood to be successfully developed, while those associated with more human pathways increase the chance of undesirable interferences with other human processes (Pharmacol Rev, 58: 259-279, 2006).

Biological Network Descriptors of target is determined based on a human protein-protein interactions (PPI) network consisting of 9,309 proteins and 52,713 PPIs, which were with a high confidence score of ≥ 0.95 collected from STRING database.

The network properties of targets based on protein-protein interactions (PPIs) have been widely adopted for the assessment of target’s druggability. Proteins with high node degree tend to have a high impact on network function through multiple interactions, while proteins with high betweenness centrality are regarded to be central for communication in interaction networks and regulate the flow of signaling information (Front Pharmacol, 9, 1245, 2018; Curr Opin Struct Biol. 44:134-142, 2017).

Human Similarity Proteins

Human Pathway Affiliation

Biological Network Descriptors

There is no similarity protein (E value < 0.005) for this target

KEGG Pathway	Pathway ID	Affiliated Target
MAPK signaling pathway	hsa04010	Affiliated Target
Class: Environmental Information Processing => Signal transduction	Pathway Hierarchy
Ras signaling pathway	hsa04014	Affiliated Target
Class: Environmental Information Processing => Signal transduction	Pathway Hierarchy
Rap1 signaling pathway	hsa04015	Affiliated Target
Class: Environmental Information Processing => Signal transduction	Pathway Hierarchy
Calcium signaling pathway	hsa04020	Affiliated Target
Class: Environmental Information Processing => Signal transduction	Pathway Hierarchy
PI3K-Akt signaling pathway	hsa04151	Affiliated Target
Class: Environmental Information Processing => Signal transduction	Pathway Hierarchy
Regulation of actin cytoskeleton	hsa04810	Affiliated Target
Class: Cellular Processes => Cell motility	Pathway Hierarchy
Click to Show/Hide the Information of Affiliated Human Pathways

Degree	2	Degree centrality	2.15E-04	Betweenness centrality	3.61E-08
Closeness centrality	1.94E-01	Radiality	1.33E+01	Clustering coefficient	0.00E+00
Neighborhood connectivity	2.90E+01	Topological coefficient	7.18E-01	Eccentricity	13
Download	Click to Download the Full PPI Network of This Target

Target Profiles in Patients

Top

Target Expression
Profile (TEP)

Target Expression Profile Info

Target Affiliated Biological Pathways		Top
KEGG Pathway	[+] 7 KEGG Pathways	+
1	MAPK signaling pathway
2	Ras signaling pathway
3	Rap1 signaling pathway
4	PI3K-Akt signaling pathway
5	Regulation of actin cytoskeleton
6	Pathways in cancer
7	Melanoma
Panther Pathway	[+] 1 Panther Pathways	+
1	FGF signaling pathway
PID Pathway	[+] 2 PID Pathways	+
1	Regulation of nuclear beta catenin signaling and target gene transcription
2	FGF signaling pathway
Reactome	[+] 29 Reactome Pathways	+
1	PI3K Cascade
2	PIP3 activates AKT signaling
3	FGFR4 ligand binding and activation
4	FGFR3c ligand binding and activation
5	FGFR2c ligand binding and activation
6	FGFR3 mutant receptor activation
7	Activated point mutants of FGFR2
8	Constitutive Signaling by Aberrant PI3K in Cancer
9	Phospholipase C-mediated cascade: FGFR1
10	Phospholipase C-mediated cascade
11	Phospholipase C-mediated cascade
12	Phospholipase C-mediated cascade
13	SHC-mediated cascade:FGFR1
14	PI-3K cascade:FGFR1
15	FRS-mediated FGFR1 signaling
16	PI-3K cascade:FGFR2
17	SHC-mediated cascade:FGFR2
18	FRS-mediated FGFR2 signaling
19	SHC-mediated cascade:FGFR3
20	FRS-mediated FGFR3 signaling
21	PI-3K cascade:FGFR3
22	FRS-mediated FGFR4 signaling
23	SHC-mediated cascade:FGFR4
24	PI-3K cascade:FGFR4
25	Negative regulation of FGFR1 signaling
26	Negative regulation of FGFR2 signaling
27	Negative regulation of FGFR3 signaling
28	Negative regulation of FGFR4 signaling
29	RAF/MAP kinase cascade
WikiPathways	[+] 6 WikiPathways	+
1	Regulation of Actin Cytoskeleton
2	MAPK Signaling Pathway
3	Differentiation Pathway
4	Signaling by Type 1 Insulin-like Growth Factor 1 Receptor (IGF1R)
5	PIP3 activates AKT signaling
6	Signaling by FGFR

References

Top

REF 1

Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.

REF 2

FDA Approved Drug Products from FDA Official Website. 2009. Application Number: (NDA) 020193.

REF 3

ClinicalTrials.gov (NCT01550614) Efficacy and Safety of Ad5FGF-4 for Myocardial Ischemia in Patients With Stable Angina Due to Coronary Artery Disease. U.S. National Institutes of Health.

REF 4

Alferminogene tadenovec, an angiogenic FGF4 gene therapy for coronary artery disease. IDrugs. 2008 Apr;11(4):283-93.

REF 5

ClinicalTrials.gov (NCT01550614) Efficacy and Safety of Ad5FGF-4 for Myocardial Ischemia in Patients With Stable Angina Due to Coronary Artery Disease (ASPIRE). U.S. National Institutes of Health.

REF 6

Angiogenic gene therapy with adenovirus 5 fibroblast growth factor-4 (Ad5FGF-4): a new option for the treatment of coronary artery disease. Am J Cardiol. 2003 Nov 7;92(9B):24N-31N.

REF 7

Effects of Ad5FGF-4 in patients with angina: an analysis of pooled data from the AGENT-3 and AGENT-4 trials. J Am Coll Cardiol. 2007 Sep 11;50(11):1038-46.

If You Find Any Error in Data or Bug in Web Service, Please Kindly Report It to Dr. Zhou and Dr. Zhang.

Prof. Feng ZHU

Prof. Yuzong CHEN