Target Information

Target General Information

Target ID

T87350 (Former ID: TTDI02317)

Target Name

Platelet-derived growth factor B (PDGFB)

Synonyms

SIS; Protooncogene cSis; Proto-oncogene c-Sis; Plateletderived growth factor subunit B; Plateletderived growth factor beta polypeptide; Plateletderived growth factor B chain; Platelet-derived growth factor subunit B; Platelet-derived growth factor beta polypeptide; Platelet-derived growth factor B chain; PDGF2; PDGF-2; PDGF subunit B; Becaplermin

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Gene Name

PDGFB

Target Type

Clinical trial target

[1]

Disease

[+] 1 Target-related Diseases

Diabetic foot ulcer [ICD-11: BD54]

Function

Potent mitogen for cells of mesenchymal origin. Required for normal proliferation and recruitment of pericytes and vascular smooth muscle cells in the central nervous system, skin, lung, heart and placenta. Required for normal blood vessel development, and for normal development of kidney glomeruli. Plays an important role in wound healing. Signaling is modulated by the formation of heterodimers with PDGFA. Growth factor that plays an essential role in the regulation of embryonic development, cell proliferation, cell migration, survival and chemotaxis.

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BioChemical Class

Growth factor

UniProt ID

PDGFB_HUMAN

Sequence

MNRCWALFLSLCCYLRLVSAEGDPIPEELYEMLSDHSIRSFDDLQRLLHGDPGEEDGAEL
DLNMTRSHSGGELESLARGRRSLGSLTIAEPAMIAECKTRTEVFEISRRLIDRTNANFLV
WPPCVEVQRCSGCCNNRNVQCRPTQVQLRPVQVRKIEIVRKKPIFKKATVTLEDHLACKC
ETVAAARPVTRSPGGSQEQRAKTPQTRVTIRTVRVRRPPKGKHRKFKHTHDKTALKETLG
A

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3D Structure

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AlphaFold

HIT2.0 ID

T89S77

Drugs and Modes of Action

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Clinical Trial Drug(s)

[+] 4 Clinical Trial Drugs

PDGF-BB

Drug Info

Phase 3

Diabetic foot ulcer

[2], [3]

E-10030

Drug Info

Phase 2

Macular degeneration

[4]

GAM-501

Drug Info

Phase 2

Diabetic foot ulcer

[5]

CR-002

Drug Info

Phase 1

Cystic fibrosis

[6]

Mode of Action

[+] 2 Modes of Action

Modulator

[+] 3 Modulator drugs

PDGF-BB

Drug Info

[1]

GAM-501

Drug Info

[8]

CR-002

Drug Info

[9]

Antagonist

[+] 1 Antagonist drugs

E-10030

Drug Info

[4], [7]

Cell-based Target Expression Variations

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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

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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
Phospholipase D signaling pathway	hsa04072	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
Focal adhesion	hsa04510	Affiliated Target
Class: Cellular Processes => Cellular community - eukaryotes	Pathway Hierarchy
Gap junction	hsa04540	Affiliated Target
Class: Cellular Processes => Cellular community - eukaryotes	Pathway Hierarchy
JAK-STAT signaling pathway	hsa04630	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	7	Degree centrality	7.52E-04	Betweenness centrality	8.09E-05
Closeness centrality	2.34E-01	Radiality	1.41E+01	Clustering coefficient	3.81E-01
Neighborhood connectivity	5.06E+01	Topological coefficient	1.76E-01	Eccentricity	12
Download	Click to Download the Full PPI Network of This Target

Target Regulators

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Target-regulating microRNAs

Target-regulating microRNAs Info

Target-regulating Transcription Factors

Target-regulating Transcription Factors Info

Target Affiliated Biological Pathways		Top
KEGG Pathway	[+] 16 KEGG Pathways	+
1	MAPK signaling pathway
2	Ras signaling pathway
3	Rap1 signaling pathway
4	Cytokine-cytokine receptor interaction
5	PI3K-Akt signaling pathway
6	Focal adhesion
7	Gap junction
8	Regulation of actin cytoskeleton
9	HTLV-I infection
10	Pathways in cancer
11	MicroRNAs in cancer
12	Renal cell carcinoma
13	Glioma
14	Prostate cancer
15	Melanoma
16	Choline metabolism in cancer
NetPath Pathway	[+] 2 NetPath Pathways	+
1	IL4 Signaling Pathway
2	TNFalpha Signaling Pathway
Panther Pathway	[+] 2 Panther Pathways	+
1	Angiogenesis
2	PDGF signaling pathway
PID Pathway	[+] 9 PID Pathways	+
1	Signaling events mediated by PTP1B
2	Beta3 integrin cell surface interactions
3	S1P3 pathway
4	Nectin adhesion pathway
5	Signaling events mediated by TCPTP
6	SHP2 signaling
7	S1P1 pathway
8	PDGFR-beta signaling pathway
9	PDGF receptor signaling network
Reactome	[+] 5 Reactome Pathways	+
1	Platelet degranulation
2	PIP3 activates AKT signaling
3	Constitutive Signaling by Aberrant PI3K in Cancer
4	Non-integrin membrane-ECM interactions
5	RAF/MAP kinase cascade
WikiPathways	[+] 12 WikiPathways	+
1	Regulation of Actin Cytoskeleton
2	MAPK Signaling Pathway
3	Osteoblast Signaling
4	Focal Adhesion
5	NRF2 pathway
6	Differentiation Pathway
7	Extracellular matrix organization
8	PIP3 activates AKT signaling
9	PDGF Pathway
10	Signaling by PDGF
11	Angiogenesis
12	Osteoclast Signaling

References

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REF 1

Clinical pipeline report, company report or official report of Adocia.

REF 2

URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 5039).

REF 3

ClinicalTrials.gov (NCT02236793) A Phase 3 Clinical Trial to Assess the Effectiveness of BioChaperone PDGF-BB In the Treatment of Chronic Diabetic Foot Ulcer. U.S. National Institutes of Health.

REF 4

ClinicalTrials.gov (NCT01089517) A Safety and Efficacy Study of E10030 (Anti-PDGF Pegylated Aptamer) Plus Lucentis for Neovascular Age-Related Macular Degeneration. U.S. National Institutes of Health.

REF 5

ClinicalTrials.gov (NCT00493051) Phase 2b Study of GAM501 in the Treatment of Diabetic Ulcers of the Lower Extremities. U.S. National Institutes of Health.

REF 6

ClinicalTrials.gov (NCT01347190) Safety and Tolerability Study of Liquid Alpha1 Proteinase Inhibitor (API) in Subjects With Cystic Fibrosis. U.S. National Institutes of Health.

REF 7

Aptamers as therapeutics. Nat Rev Drug Discov. 2010 Jul;9(7):537-50.

REF 8

Treatment of nonhealing diabetic foot ulcers with a platelet-derived growth factor gene-activated matrix (GAM501): results of a phase 1/2 trial. Wound Repair Regen. 2009 Nov-Dec;17(6):772-9.

REF 9

A phase I study of CR002, a fully-human monoclonal antibody against platelet-derived growth factor-D. Int J Clin Pharmacol Ther. 2008 May;46(5):236-44.

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