PDGFB

Summary

PDGFB (platelet derived growth factor subunit B, HGNC:8800) is a protein-coding gene on chromosome 22q13.1, encoding Platelet-derived growth factor subunit B (P01127). Growth factor that plays an essential role in the regulation of embryonic development, cell proliferation, cell migration, survival and chemotaxis.

This gene encodes a member of the protein family comprised of both platelet-derived growth factors (PDGF) and vascular endothelial growth factors (VEGF). The encoded preproprotein is proteolytically processed to generate platelet-derived growth factor subunit B, which can homodimerize, or alternatively, heterodimerize with the related platelet-derived growth factor subunit A. These proteins bind and activate PDGF receptor tyrosine kinases, which play a role in a wide range of developmental processes. Mutations in this gene are associated with meningioma. Reciprocal translocations between chromosomes 22 and 17, at sites where this gene and that for collagen type 1, alpha 1 are located, are associated with dermatofibrosarcoma protuberans, a rare skin tumor. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 5155 — RefSeq curated summary.

At a glance

• Gene–disease (curated): basal ganglia calcification, idiopathic, 5 (Strong, GenCC) — +2 more curated relationships
• GWAS associations: 2
• Clinical variants (ClinVar): 204 total — 16 pathogenic, 11 likely-pathogenic
• Phenotypes (HPO): 142
• Druggable target: yes
• Transcription factor: yes — 13 downstream targets (CollecTRI)
• MANE Select transcript: NM_002608

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:8800
Approved symbol	PDGFB
Name	platelet derived growth factor subunit B
Location	22q13.1
Locus type	gene with protein product
Status	Approved
Aliases	SSV
Ensembl gene	ENSG00000100311
Ensembl biotype	protein_coding
OMIM	190040
Entrez	5155

Gene structure

Transcript identifiers

Ensembl transcripts: 7 — 7 protein_coding

ENST00000331163, ENST00000381551, ENST00000440375, ENST00000455790, ENST00000921091, ENST00000921092, ENST00000971907

RefSeq mRNA: 2 — MANE Select: NM_002608 NM_002608, NM_033016

CCDS: CCDS13987, CCDS33650

Canonical transcript exons

ENST00000331163 — 7 exons

Exon	Start	End
ENSE00000654697	39231622	39231827
ENSE00000654698	39233435	39233524
ENSE00000880349	39225695	39225847
ENSE00001121630	39243901	39244982
ENSE00001355284	39223359	39225313
ENSE00001877460	39230084	39230228
ENSE00003510240	39235778	39235874

Expression profiles

Bgee: expression breadth ubiquitous, 259 present calls, max score 92.66.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 16.6304 / max 872.8524, expressed in 1109 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
194276	15.4422	1011
194273	0.5902	340
194275	0.2023	116
194272	0.2021	102
194274	0.1934	104

Top tissues by expression

285 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
olfactory bulb	UBERON:0002264	92.66	silver quality
type B pancreatic cell	CL:0000169	92.04	silver quality
apex of heart	UBERON:0002098	90.44	gold quality
pancreatic ductal cell	CL:0002079	89.57	gold quality
omental fat pad	UBERON:0010414	89.37	gold quality
peritoneum	UBERON:0002358	89.34	gold quality
adipose tissue of abdominal region	UBERON:0007808	88.70	gold quality
right lung	UBERON:0002167	88.47	gold quality
vena cava	UBERON:0004087	87.96	gold quality
subcutaneous adipose tissue	UBERON:0002190	87.75	gold quality
triceps brachii	UBERON:0001509	87.28	silver quality
heart left ventricle	UBERON:0002084	87.23	gold quality
upper lobe of left lung	UBERON:0008952	87.11	gold quality
cardiac ventricle	UBERON:0002082	87.10	gold quality
upper lobe of lung	UBERON:0008948	86.55	gold quality
cervix squamous epithelium	UBERON:0006922	86.39	silver quality
right lobe of thyroid gland	UBERON:0001119	86.24	gold quality
metanephros cortex	UBERON:0010533	86.23	gold quality
gluteal muscle	UBERON:0002000	86.21	silver quality
adipose tissue	UBERON:0001013	85.88	gold quality
right atrium auricular region	UBERON:0006631	85.61	gold quality
connective tissue	UBERON:0002384	85.17	gold quality
cardiac atrium	UBERON:0002081	85.02	gold quality
parotid gland	UBERON:0001831	84.89	silver quality
heart	UBERON:0000948	84.75	gold quality
lower esophagus muscularis layer	UBERON:0035833	84.52	gold quality
lower esophagus	UBERON:0013473	84.45	gold quality
muscle layer of sigmoid colon	UBERON:0035805	84.34	gold quality
diaphragm	UBERON:0001103	83.99	gold quality
sural nerve	UBERON:0015488	83.79	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-MTAB-8205	yes	105.54
E-ANND-3	yes	9.36

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

13 targets.

Target	Regulation
ACTA2	Repression
CDK4	Activation
HAS1	Activation
HAS2	Activation
HAS3	Activation
HDAC1	Activation
HYAL1	Activation
HYAL2	Activation
NR4A3	Activation
PPARG	Activation
PRKCD	Activation
PRKCQ	Activation
TAGLN	Repression

Upstream regulators (CollecTRI, top): DNMT1, E2F1, EGR1, ELK1, EPAS1, ESR2, FOS, FOXN1, FOXO1, FOXO3, HIF1A, JUN, KLF5, NFKB1, NFKB, PAX3, SMAD2, SMAD3, SMAD4, SP1, SP3, SPI1, STAT1, STAT3, TP73, VHL, VSX2, YBX1, ZNF174

miRNA regulators (miRDB)

112 targeting PDGFB, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-6851-5P	100.00	65.63	1294
HSA-MIR-3689D	100.00	66.14	1181
HSA-MIR-4692	100.00	67.32	2066
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-1252-5P	100.00	69.80	2774
HSA-MIR-29A-3P	100.00	73.11	1835
HSA-MIR-29B-3P	100.00	73.18	1833
HSA-MIR-29C-3P	100.00	73.15	1833
HSA-MIR-6758-5P	100.00	66.21	1470
HSA-MIR-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-450A-1-3P	100.00	69.33	1837
HSA-MIR-3925-3P	100.00	69.95	1237
HSA-MIR-4533	100.00	69.48	2758
HSA-MIR-4500	99.99	72.72	2367
HSA-MIR-4514	99.99	67.10	1870
HSA-LET-7A-5P	99.98	72.29	1790
HSA-LET-7B-5P	99.98	72.31	1790
HSA-LET-7C-5P	99.98	72.29	1790
HSA-LET-7E-5P	99.98	72.29	1790
HSA-LET-7F-5P	99.98	72.56	1784
HSA-LET-7G-5P	99.98	72.37	1784
HSA-LET-7I-5P	99.98	72.37	1788
HSA-MIR-98-5P	99.98	72.33	1787
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-LET-7D-5P	99.96	71.76	1632
HSA-MIR-4458	99.96	71.64	1650
HSA-MIR-6780B-5P	99.96	69.60	2562
HSA-MIR-4725-3P	99.96	69.53	2520

Literature-anchored findings (GeneRIF, showing 40)

• The sequential activation and repression of the human PDGF-B gene during chronic hypoxia reveals antagonistic roles for the depletion of oxygen and glucose (PMID:11811779)
• Fusion of COL1A1 exon 29 with PDGFB exon 2 in a der(22)t(17;22) in a pediatric giant cell fibroblastoma with a pigmented Bednar tumor component. Evidence for age-related chromosomal pattern in dermatofibrosarcoma protuberans and related tumors. (PMID:12034531)
• A fusion of COLIA1 exon 24 in frame with PDGFB exon 2 was found in a complex marker chromosome from dermatofibrosarcoma protuberans with sequences from chromosomes 7,8,17,21, & 22. (PMID:12127408)
• determination of PDGFB expression levels in medulloblastoma tumor cell lines (PMID:12176024)
• involvement of Furin gene regulation in the maturation of PDGF-AB in differentiating megakaryoblastic cells (PMID:12411321)
• PDGF and similar cytokines may be important factors in airway remodeling by redistribution of smooth muscle cells during inflammation and that urokinase may be important in potentiating the response. (PMID:12576295)
• The preferential formation of disulfide-bonded heterodimers from an equimolar mixture of unfolded A- and B-chains is thus a kinetically controlled process (PMID:12615918)
• PDGFB enhances wound closure in the absence of wound contraction. (PMID:12850807)
• a time-dependent release of TGFB and PDGF-AB occurred at neutral and alkaline pH, but not pH5, 15 min and 12h after platelet activation, suggesting relevance to wound healing (PMID:12850832)
• propose that the TATA-containing P0 promoter and the 5’-UTR promoter work together to tightly control the expression of PDGF-B (PMID:12960151)
• role in dermal fibroblast migration (PMID:14595114)
• The COL1A1-PDGFB fusion transcripts were detected from the tumor specimens. Sequence analysis revealed that the ends of exons 42, 29 and 38 in the COL1A1 gene were fused with the start of exon 2 in the PDGFB gene in case 1, 2 and 3, respectively. (PMID:14643521)
• cultured follicular keratinocytes synthesize both PDGF-A and PDGF-B, whereas, dermal papilla cells only express PDGF-A. (PMID:14705808)
• PDGF-BB may play some role in the development and progression of liver fibrosis (PMID:14760763)
• PDGFB autocrine inhibition is associated with malignant gliomas (PMID:14997209)
• biological consequences of the mutant PDGFB allele contributed to the unique disease phenotype of the translocation patient (PMID:15081117)
• Overexpression of caveolin-1 in mesangial cells suppresses MAP kinase activation and cell proliferation induced by bFGF and PDGF, two major cytokines in mesangioproliferative nephritis(MN). Caveolin-1 expression vector is potential therapy for MN. (PMID:15496150)
• Data demonstrate that type I collagen synergistically enhances platelet-derived growth factor (PDGF)-induced smooth muscle cell proliferation through Src-dependent crosstalk between the alpha2beta1 integrin and the PDGF receptor beta. (PMID:15522237)
• Data show that constitutive expression of platelet-derived growth factor-BB leads to malignant transformation in nude mice. (PMID:15695519)
• WAVE3-mediated migration in MDA-MB-231 cells via lamellipodia formation is activated downstream of PI3K and induced by PDGF (PMID:15826941)
• NAD(P)H oxidase is expressed in hepatic stellate cells and produces reactive oxygen species via activation of NAD(P)H oxidase in response to the homodimeric complex of PDGF-B, PDGF-BB. (PMID:15915457)
• EWS-Fli1 may play a role in the regulation of PDGF-induced tumor proliferation-signaling enzymes via PLD2 expression in Ewing sarcoma cells (PMID:15919668)
• In the aneurysmal wall of IAAA, weak expressions of PDGF A and B chains were observed in endothelial cells of vessel walls around the inflammatory cells, but the intensity of expression was much weaker than that on the vessel walls in AAAA. (PMID:15956925)
• findings emphasize the importance of the convertase-directed processing of proPDGF-B at the RGRR81/ sequence for PDGF-B maturation and secretion (PMID:16007151)
• in primary fibroblasts stabilization of Ras protein by ROS and ERK1/2 amplifies the response of the cells to growth factors and in systemic sclerosis represents a critical factor in the onset and progression of the disease (PMID:16081426)
• PDGF-BB/PDGF-R interaction is vital in nicotine’s mitogenic actions on human aortic smooth muscle cells (PMID:16149045)
• Expression of PDGF-B and PDGF-Rbeta suggests that autocrine signaling of PDGF may be important in malignant transformation of B-CLL. (PMID:16227675)
• PDGF-B gene polymorphism appears to be associated with severe recurrent HCV infection after liver transplantation. (PMID:16477226)
• Overexpression of PDGF-B was associated with peripheral blood, sentinel lymph node and bone marrow micro-metastasis in breast cancer (PMID:16596190)
• PDGF-BB and TGF-beta1 binding to intact alpha2M is specific, involving a defined region of the alpha2M subunit (PMID:16641085)
• In this review, the interaction of PDGF-B with heparan sulfate proteoglycans is implicated in the process of diffusion, and thus the availability, of PDGF-B that is needed for pericyte recruitment around newly formed capillaries. (PMID:16709185)
• report suggests that in humans, platelet-derived growth factor(PDGF) and downstream activation of protein kinase C could represent an important control for natriuretic peptide precursor C expression in vascular smooth muscle (PMID:16777970)
• Fluorescence in situ hybridization (FISH) analysis demonstrated the COL1A1-PDGFB fusion on both der(22) chromosomes. [Col1A1-PDGFB fusion protein] (PMID:16843106)
• PDGF significantly upregulates neuropilin-1 mRNA expression and protein production in aortic smooth muscle cells (PMID:16847823)
• GRX plays an important role in PDGF-BB-dependent cell proliferation by regulating the redox state of LMW-PTP (PMID:16893901)
• The level of PDGF-BB in obstructive sleep apnea-hypopnea syndrome is elevated. (PMID:17074267)
• The mRNA levels of PDGFB were significantly produced by the megakaryocytes may be associated with the etiology of bone marrow fibrosis in AMM. (PMID:17157157)
• Copy gain of PDGFB occurs in a subset of tumors showing no evidence of mutated BRAF or rearranged ret, suggesting that copy gain of PDGFB may underlie the increased expression of platelet-derived growth factor described recently in the literature. (PMID:17227125)
• N-cadherin and beta-catenin play role in cell migration via PDGF-Rbeta-mediated signaling through the scaffolding molecule NHERF2 (PMID:17229887)
• Induction of PDGF-B is associated with glioma (PMID:17292826)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	pdgfbb	ENSDARG00000038139
danio_rerio	pdgfba	ENSDARG00000086778
mus_musculus	Pdgfb	ENSMUSG00000000489
rattus_norvegicus	Pdgfb	ENSRNOG00000017197
drosophila_melanogaster	Pvf1	FBGN0030964
caenorhabditis_elegans		WBGENE00004249

Paralogs (1): PDGFA (ENSG00000197461)

Protein

Protein identifiers

Platelet-derived growth factor subunit B — P01127 (reviewed: P01127)

Alternative names: PDGF-2, Platelet-derived growth factor B chain, Platelet-derived growth factor beta polypeptide, Proto-oncogene c-Sis

All UniProt accessions (4): P01127, A0A384NYY3, A9UJN9, A9UJP0

UniProt curated annotations — full annotation on UniProt →

Function. Growth factor that plays an essential role in the regulation of embryonic development, cell proliferation, cell migration, survival and chemotaxis. 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.

Subunit / interactions. Antiparallel homodimer; disulfide-linked. Antiparallel heterodimer with PDGFA; disulfide-linked. The PDGFB homodimer interacts with PDGFRA and PDGFRB homodimers, and with heterodimers formed by PDGFRA and PDGFRB. The heterodimer composed of PDGFA and PDGFB interacts with PDGFRB homodimers, and with heterodimers formed by PDGFRA and PDGFRB. Interacts with XLKD1. Interacts with LRP1. Interacts with SORL1 (via the N-terminal ectodomain). Interacts with CD82; this interaction inhibits PDGFB-mediated signaling pathway.

Subcellular location. Secreted.

Tissue specificity. Expressed at high levels in the heart, brain (sustantia nigra), placenta and fetal kidney. Expressed at moderate levels in the brain (hippocampus), skeletal muscle, kidney and lung.

Disease relevance. Basal ganglia calcification, idiopathic, 5 (IBGC5) [MIM:615483] A form of basal ganglia calcification, an autosomal dominant condition characterized by symmetric calcification in the basal ganglia and other brain regions. Affected individuals can either be asymptomatic or show a wide spectrum of neuropsychiatric symptoms, including parkinsonism, dystonia, tremor, ataxia, dementia, psychosis, seizures, and chronic headache. Serum levels of calcium, phosphate, alkaline phosphatase and parathyroid hormone are normal. The neuropathological hallmark of the disease is vascular and pericapillary calcification, mainly of calcium phosphate, in the affected brain areas. The disease is caused by variants affecting the gene represented in this entry. A chromosomal aberration involving PDGFB is found in dermatofibrosarcoma protuberans. Translocation t(17;22)(q22;q13) with PDGFB.

Similarity. Belongs to the PDGF/VEGF growth factor family.

Isoforms (2)

UniProt ID	Names	Canonical?
P01127-1	1	yes
P01127-2	2

RefSeq proteins (2): NP_002599, NP_148937 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000072	PDGF/VEGF_dom	Domain
IPR006782	PDGF_N	Domain
IPR023581	PD_growth_factor_CS	Conserved_site
IPR029034	Cystine-knot_cytokine	Homologous_superfamily

Pfam: PF00341, PF04692

UniProt features (27 total): disulfide bond 5, strand 5, sequence variant 3, sequence conflict 3, propeptide 2, site 2, signal peptide 1, splice variant 1, chain 1, helix 1, region of interest 1, compositionally biased region 1, glycosylation site 1

Structure

Experimental structures (PDB)

6 structures.

PDB	Method	Resolution (Å)
4HQU	X-RAY DIFFRACTION	2.2
3MJG	X-RAY DIFFRACTION	2.3
4HQX	X-RAY DIFFRACTION	2.3
4QCI	X-RAY DIFFRACTION	2.3
6T9E	X-RAY DIFFRACTION	2.99
1PDG	X-RAY DIFFRACTION	3

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P01127-F1	73.77	0.35

Antibody-complex structures (SAbDab): 2 — 4QCI, 6T9E

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Catalytic / active sites (2): 108 (involved in receptor binding); 111 (involved in receptor binding)

Disulfide bonds (5): 124, 130–178, 133, 134–180, 97–141

Glycosylation sites (1): 63

Function

Pathways and Gene Ontology

Reactome pathways

8 pathways

ID	Pathway
R-HSA-114608	Platelet degranulation
R-HSA-1257604	PIP3 activates AKT signaling
R-HSA-186763	Downstream signal transduction
R-HSA-186797	Signaling by PDGF
R-HSA-2219530	Constitutive Signaling by Aberrant PI3K in Cancer
R-HSA-3000171	Non-integrin membrane-ECM interactions
R-HSA-5673001	RAF/MAP kinase cascade
R-HSA-6811558	PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling

MSigDB gene sets: 0 (showing top):

GO Biological Process (61): angiogenesis (GO:0001525), embryonic placenta development (GO:0001892), positive regulation of endothelial cell proliferation (GO:0001938), monocyte chemotaxis (GO:0002548), positive regulation of glomerular filtration (GO:0003104), protein phosphorylation (GO:0006468), heart development (GO:0007507), positive regulation of cell population proliferation (GO:0008284), response to wounding (GO:0009611), gene expression (GO:0010467), negative regulation of phosphatidylinositol biosynthetic process (GO:0010512), negative regulation of platelet activation (GO:0010544), positive regulation of gene expression (GO:0010628), negative regulation of gene expression (GO:0010629), positive regulation of cell-substrate adhesion (GO:0010811), smooth muscle adaptation (GO:0014805), positive regulation of smooth muscle cell migration (GO:0014911), peptidyl-tyrosine phosphorylation (GO:0018108), positive regulation of cell migration (GO:0030335), intracellular signal transduction (GO:0035556), interleukin-18-mediated signaling pathway (GO:0035655), positive regulation of metanephric mesenchymal cell migration by platelet-derived growth factor receptor-beta signaling pathway (GO:0035793), cellular response to platelet-derived growth factor stimulus (GO:0036120), paracrine signaling (GO:0038001), positive regulation of MAP kinase activity (GO:0043406), positive regulation of MAPK cascade (GO:0043410), positive regulation of blood vessel endothelial cell migration (GO:0043536), positive regulation of mitotic nuclear division (GO:0045840), negative regulation of DNA-templated transcription (GO:0045892), positive regulation of DNA-templated transcription (GO:0045893), platelet-derived growth factor receptor signaling pathway (GO:0048008), positive regulation of fibroblast proliferation (GO:0048146), positive regulation of smooth muscle cell proliferation (GO:0048661), positive regulation of chemotaxis (GO:0050921), positive regulation of cell division (GO:0051781), positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction (GO:0051897), cell chemotaxis (GO:0060326), positive regulation of ERK1 and ERK2 cascade (GO:0070374), cellular response to growth factor stimulus (GO:0071363), cellular response to mycophenolic acid (GO:0071506)

GO Molecular Function (11): platelet-derived growth factor receptor binding (GO:0005161), collagen binding (GO:0005518), growth factor activity (GO:0008083), superoxide-generating NADPH oxidase activator activity (GO:0016176), chemoattractant activity (GO:0042056), identical protein binding (GO:0042802), protein homodimerization activity (GO:0042803), protein heterodimerization activity (GO:0046982), platelet-derived growth factor binding (GO:0048407), protein binding (GO:0005515), receptor ligand activity (GO:0048018)

GO Cellular Component (12): Golgi membrane (GO:0000139), extracellular region (GO:0005576), obsolete extracellular space (GO:0005615), cytoplasm (GO:0005737), endoplasmic reticulum lumen (GO:0005788), Golgi lumen (GO:0005796), cell surface (GO:0009986), basolateral plasma membrane (GO:0016323), extracellular matrix (GO:0031012), platelet alpha granule lumen (GO:0031093), platelet-derived growth factor complex (GO:1990265), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-8 pathways:

Category	Pathways
Response to elevated platelet cytosolic Ca2+	1
Intracellular signaling by second messengers	1
Signaling by PDGF	1
Signaling by Receptor Tyrosine Kinases	1
PI3K/AKT Signaling in Cancer	1
Extracellular matrix organization	1
MAPK1/MAPK3 signaling	1
Negative regulation of the PI3K/AKT network	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
gene expression	2
regulation of gene expression	2
intracellular anatomical structure	2
signal transduction	2
receptor ligand activity	2
protein dimerization activity	2
Golgi apparatus	2
intracellular organelle lumen	2
blood vessel morphogenesis	1
anatomical structure formation involved in morphogenesis	1
in utero embryonic development	1
placenta development	1
embryonic organ development	1
endothelial cell proliferation	1
regulation of endothelial cell proliferation	1
positive regulation of epithelial cell proliferation	1
leukocyte chemotaxis	1
mononuclear cell migration	1
myeloid leukocyte migration	1
regulation of glomerular filtration	1
glomerular filtration	1
positive regulation of multicellular organismal process	1
phosphorylation	1
protein modification process	1
animal organ development	1
circulatory system development	1
cell population proliferation	1
regulation of cell population proliferation	1
positive regulation of cellular process	1
response to stress	1
macromolecule biosynthetic process	1
phosphatidylinositol biosynthetic process	1
negative regulation of biosynthetic process	1
regulation of phosphatidylinositol biosynthetic process	1
negative regulation of phosphorus metabolic process	1
regulation of platelet activation	1
platelet activation	1
negative regulation of blood coagulation	1
negative regulation of cell activation	1

Protein interactions and networks

STRING

2242 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PDGFB	PDGFRB	P09619	999
PDGFB	PDGFRA	P16234	996
PDGFB	PDGFA	P04085	982
PDGFB	PDGFC	Q9NRA1	968
PDGFB	FGF2	P09038	923
PDGFB	PDGFD	Q9GZP0	911
PDGFB	FGF13	Q92913	831
PDGFB	COL1A1	P02452	828
PDGFB	AKT1	P31749	782
PDGFB	ANGPT1	Q15389	767
PDGFB	KDR	P35968	757
PDGFB	FGF8	P55075	745
PDGFB	FLT1	P16057	739
PDGFB	TGFB1	P01137	727
PDGFB	HIF1A	Q16665	717

IntAct

43 interactions, top by confidence:

A	B	Type	Score
PDGFRB	PDGFB	psi-mi:“MI:0915”(physical association)	0.900
PDGFB	PDGFRB	psi-mi:“MI:0407”(direct interaction)	0.900
PDGFRB	PDGFB	psi-mi:“MI:0407”(direct interaction)	0.900
PDGFB	PDGFRB	psi-mi:“MI:0915”(physical association)	0.900
PDGFB	PDGFB	psi-mi:“MI:0407”(direct interaction)	0.730
PDGFRA	PDGFB	psi-mi:“MI:0915”(physical association)	0.730
PDGFB	PDGFRA	psi-mi:“MI:0407”(direct interaction)	0.730
PDGFRA	PDGFB	psi-mi:“MI:0407”(direct interaction)	0.730

BioGRID (139): PDGFB (Affinity Capture-Western), PDGFB (Affinity Capture-Western), PDGFB (Reconstituted Complex), PDGFB (Reconstituted Complex), PDGFB (Reconstituted Complex), PDGFB (Reconstituted Complex), FAT3 (Affinity Capture-MS), DDX54 (Affinity Capture-MS), C11orf57 (Affinity Capture-MS), ZC3H4 (Affinity Capture-MS), MRPS18C (Affinity Capture-MS), GPR98 (Affinity Capture-MS), RPL26L1 (Affinity Capture-MS), MRPS35 (Affinity Capture-MS), MRPS9 (Affinity Capture-MS)

ESM2 similar proteins: A4IIA2, A5A6L1, B3F211, O00622, O35251, O43915, O61307, O93525, P01127, P08833, P12843, P15473, P16612, P18406, P21743, P24591, P24593, P24594, P31240, P47876, P47877, P49011, Q05717, Q06481, Q07079, Q28985, Q29400, Q5XHC5, Q66K08, Q6Q484, Q6Q7I7, Q76LD0, Q8BLY1, Q8CD91, Q90WV8, Q90ZD5, Q920C1, Q95229, Q99PS1, Q9BU40

Diamond homologs: B0VXV3, B0VXV4, C0HM96, C0K3N1, C0K3N2, C0K3N3, O35251, O35757, O43915, P01127, P01128, P04085, P0DL42, P0DW97, P0DW98, P12919, P13698, P15691, P15692, P16612, P20033, P28576, P31240, P34007, P49763, P49764, P49765, P49767, P50412, P52584, P67860, P67861, P67862, P67863, P82475, P83906, P83942, P97946, P97953, Q00731

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
PDGFB	“up-regulates activity”	PDGFRA	binding
PDGFB	up-regulates	PDGFRB	binding

Disease & clinical

Cancer significance

Clinical variants and AI predictions

ClinVar

204 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	16
Likely pathogenic	11
Uncertain significance	85
Likely benign	47
Benign	30

Top pathogenic / likely-pathogenic (27)

Variant ID	HGVS	Classification
12598	NM_002608.4(PDGFB):c.602-1396_602-1262del	Pathogenic
12599	PDGFB, PDGFB/COL1A1 FUSION	Pathogenic
1320974	NM_002608.4(PDGFB):c.457-2A>G	Pathogenic
1384828	NM_002608.4(PDGFB):c.18_19dup (p.Leu7fs)	Pathogenic
2014034	NM_002608.4(PDGFB):c.512del (p.Thr171fs)	Pathogenic
2030849	NM_002608.4(PDGFB):c.589C>T (p.Gln197Ter)	Pathogenic
2874449	NM_002608.4(PDGFB):c.385C>T (p.Arg129Cys)	Pathogenic
379331	NM_002608.4(PDGFB):c.2T>G (p.Met1Arg)	Pathogenic
4710847	NM_002608.4(PDGFB):c.33_34del (p.Cys12fs)	Pathogenic
4729161	NM_002608.4(PDGFB):c.107_110del (p.His36fs)	Pathogenic
4819278	NM_002608.4(PDGFB):c.64-50_160+533del	Pathogenic
75237	NM_002608.4(PDGFB):c.433C>T (p.Gln145Ter)	Pathogenic
75239	NM_002608.4(PDGFB):c.356T>C (p.Leu119Pro)	Pathogenic
75241	NM_002608.4(PDGFB):c.726G>C (p.Ter242Tyr)	Pathogenic
75243	NM_002608.4(PDGFB):c.445C>T (p.Arg149Ter)	Pathogenic
75245	NM_002608.4(PDGFB):c.3G>A (p.Met1Ile)	Pathogenic
2505942	NM_002608.4(PDGFB):c.724T>C (p.Ter242Gln)	Likely pathogenic
2737046	NM_002608.4(PDGFB):c.26T>G (p.Leu9Arg)	Likely pathogenic
2920727	NM_002608.4(PDGFB):c.-373C>G	Likely pathogenic
2920728	NM_002608.4(PDGFB):c.-318C>T	Likely pathogenic
3723983	NM_002608.4(PDGFB):c.232C>T (p.Arg78Cys)	Likely pathogenic
4718018	NM_002608.4(PDGFB):c.63+1G>A	Likely pathogenic
4812892	NM_002608.4(PDGFB):c.251-1G>T	Likely pathogenic
809371	NM_002608.4(PDGFB):c.457-1G>C	Likely pathogenic
916191	GRCh37/hg19 22q13.1(chr22:39629440-39639968)x1	Likely pathogenic
976390	NM_002608.4(PDGFB):c.1A>G (p.Met1Val)	Likely pathogenic
988462	NM_002608.4(PDGFB):c.512C>T (p.Thr171Met)	Likely pathogenic

SpliceAI

1238 predictions. Top by Δscore:

Variant	Effect	Δscore
22:39225709:T:A	donor_gain	1.0000
22:39225739:T:TA	donor_gain	1.0000
22:39225843:TTTGG:T	acceptor_gain	1.0000
22:39225844:TTGG:T	acceptor_gain	1.0000
22:39225845:TGG:T	acceptor_gain	1.0000
22:39225846:GG:G	acceptor_gain	1.0000
22:39225846:GGCTG:G	acceptor_loss	1.0000
22:39225847:GC:G	acceptor_loss	1.0000
22:39225848:C:CC	acceptor_gain	1.0000
22:39225848:C:T	acceptor_loss	1.0000
22:39225849:T:A	acceptor_loss	1.0000
22:39225851:C:CT	acceptor_gain	1.0000
22:39225853:C:CT	acceptor_gain	1.0000
22:39225854:A:T	acceptor_gain	1.0000
22:39230079:GTTA:G	donor_loss	1.0000
22:39230080:TTA:T	donor_loss	1.0000
22:39230081:TA:T	donor_loss	1.0000
22:39230083:C:T	donor_loss	1.0000
22:39230083:CCTCG:C	donor_gain	1.0000
22:39230146:CA:C	donor_gain	1.0000
22:39230224:CTCAC:C	acceptor_gain	1.0000
22:39230229:C:CA	acceptor_loss	1.0000
22:39231620:ACCTG:A	donor_loss	1.0000
22:39231621:C:CG	donor_loss	1.0000
22:39231823:GGAAC:G	acceptor_gain	1.0000
22:39231824:GAAC:G	acceptor_gain	1.0000
22:39231825:AAC:A	acceptor_gain	1.0000
22:39231825:AACC:A	acceptor_loss	1.0000
22:39231826:AC:A	acceptor_gain	1.0000
22:39231827:CC:C	acceptor_gain	1.0000

AlphaMissense

1549 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
22:39231656:C:G	C141S	0.999
22:39231657:A:T	C141S	0.999
22:39231788:C:G	C97S	0.999
22:39231789:A:T	C97S	0.999
22:39230152:C:G	C178S	0.998
22:39230153:A:T	C178S	0.998
22:39231657:A:G	C141R	0.998
22:39231684:C:A	G132C	0.998
22:39231689:C:G	C130S	0.998
22:39231690:A:T	C130S	0.998
22:39231789:A:G	C97R	0.998
22:39230146:C:G	C180S	0.997
22:39230147:A:T	C180S	0.997
22:39231626:A:T	V151D	0.997
22:39231677:C:T	C134Y	0.997
22:39231683:C:T	G132D	0.997
22:39231690:A:G	C130R	0.997
22:39231692:C:G	R129P	0.997
22:39231714:G:A	P122S	0.997
22:39231724:G:C	F118L	0.997
22:39231724:G:T	F118L	0.997
22:39231726:A:G	F118L	0.997
22:39231787:G:C	C97W	0.997
22:39230152:C:T	C178Y	0.996
22:39230153:A:G	C178R	0.996
22:39231655:G:C	C141W	0.996
22:39231676:G:C	C134W	0.996
22:39231677:C:G	C134S	0.996
22:39231678:A:T	C134S	0.996
22:39231688:G:C	C130W	0.996

dbSNP variants (sampled 300 via entrez): RS1000078740 (22:39222996 T>C), RS1000306354 (22:39241401 G>A), RS1000347946 (22:39243146 C>CG), RS1000349963 (22:39228216 G>A), RS1000378188 (22:39241070 G>C,T), RS1000640769 (22:39243208 G>C), RS1000713693 (22:39242966 G>A), RS1000801535 (22:39244026 G>A), RS1000910372 (22:39238948 G>A), RS1001047125 (22:39229551 G>A), RS1001050501 (22:39233005 C>T), RS1001089712 (22:39244228 G>A), RS1001102256 (22:39232800 C>T), RS1001153281 (22:39232638 T>A,C), RS1001347731 (22:39242164 CGT>C)

Disease associations

OMIM: gene MIM:190040 | disease phenotypes: MIM:615483, MIM:607907, MIM:607174, MIM:213600, MIM:606656

GenCC curated gene-disease

Disease	Classification	Inheritance
basal ganglia calcification, idiopathic, 5	Strong	Autosomal dominant
bilateral striopallidodentate calcinosis	Supportive	Autosomal dominant
familial meningioma	Limited	Autosomal dominant

Mondo (7): basal ganglia calcification, idiopathic, 5 (MONDO:0014204), meningioma (MONDO:0016642), dermatofibrosarcoma protuberans (MONDO:0011934), familial meningioma (MONDO:0011789), basal ganglia calcification, idiopathic, 1 (MONDO:0024538), hereditary breast ovarian cancer syndrome (MONDO:0003582), bilateral striopallidodentate calcinosis (MONDO:0008947)

Orphanet (5): Bilateral striopallidodentate calcinosis (Orphanet:1980), Meningioma (Orphanet:2495), Dermatofibrosarcoma protuberans (Orphanet:31112), Familial multiple meningioma (Orphanet:263662), Hereditary breast and/or ovarian cancer syndrome (Orphanet:145)

HPO phenotypes

142 total (30 of 142 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000012	Urinary urgency
HP:0000020	Urinary incontinence
HP:0000044	Hypogonadotropic hypogonadism
HP:0000141	Amenorrhea
HP:0000238	Hydrocephalus
HP:0000298	Mask-like facies
HP:0000360	Tinnitus
HP:0000520	Proptosis
HP:0000602	Ophthalmoplegia
HP:0000618	Blindness
HP:0000709	Psychosis
HP:0000712	Emotional lability
HP:0000716	Depression
HP:0000726	Dementia
HP:0000739	Anxiety
HP:0000741	Apathy
HP:0000751	Personality changes
HP:0000802	Impotence
HP:0000822	Hypertension
HP:0000870	Increased circulating prolactin concentration
HP:0001067	Neurofibroma
HP:0001072	Thickened skin
HP:0001085	Papilledema
HP:0001250	Seizure
HP:0001251	Ataxia
HP:0001260	Dysarthria
HP:0001262	Excessive daytime somnolence
HP:0001263	Global developmental delay
HP:0001266	Choreoathetosis

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST003129_13	Primary biliary cholangitis	2.000000e-11
GCST005581_18	Primary biliary cirrhosis	1.000000e-13

MeSH disease descriptors (6)

Descriptor	Name	Tree numbers
D018223	Dermatofibrosarcoma	C04.557.450.565.590.350.320; C04.557.450.795.350.320
D061325	Hereditary Breast and Ovarian Cancer Syndrome	C04.588.180.483; C04.588.322.455.431; C04.700.517; C12.050.351.500.056.630.705.431; C12.050.351.937.418.685.431; C12.100.250.056.630.705.431; C12.900.418.685.431; C16.320.700.517; C17.800.090.500.483; C19.344.410.431; C19.391.630.705.431
D008579	Meningioma	C04.557.580.520; C04.557.645.520; C04.588.614.250.580.500; C10.551.240.500.500
C537657	Basal ganglia calcification, idiopathic 2 (supp.)
C536275	Fahr’s disease (supp.)
C537443	Meningioma, familial (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL3108633 (SINGLE PROTEIN)

PharmGKB: 1 entry (VIP=true, CPIC=false)

Binding affinities (BindingDB)

226 measured of 230 human assays (231 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
3-[(Z)-2-fluoro-2-{5-[(1-methylpiperidin-4-yl)amino]pyridin-3-yl}ethenyl]-N-[(1S,2S)-2-hydroxycyclohexyl]-4-methylbenzamide	IC50	1 nM	US-12509424: Compound and composition as PDGF receptor kinase inhibitor
N-[(1R,2S)-2-hydroxycyclohexyl]-N’-[4-methyl-3-({[5-(pyrimidin-2-yl)pyridin-3-yl]amino}methyl)phenyl]urea	IC50	2.6 nM	US-12509424: Compound and composition as PDGF receptor kinase inhibitor
2-[(2-cyclopropylethyl)amino]-N-(5-{[(1S,2S)-2-hydroxycyclohexyl]carbamoyl}-2-methylphenyl)-1,3-thiazole-5-carboxamide	IC50	4.6 nM	US-12509424: Compound and composition as PDGF receptor kinase inhibitor
5-(cyclopropylamino)-N-(5-{[(1S,2S)-2-hydroxycyclohexyl]carbamoyl}-2-methylphenyl)pyridine-3-carboxamide	IC50	4.9 nM	US-12509424: Compound and composition as PDGF receptor kinase inhibitor
3-(2-amino-7,8-dihydropyrido[4,3-d]pyrimidin-6(5H)-yl)-N-[(1S,2S)-1,3-dihydroxy-1-phenylpropan-2-yl]-4-methylbenzamide	IC50	5 nM	US-12509424: Compound and composition as PDGF receptor kinase inhibitor
4-fluoro-3-[(Z)-2-fluoro-2-{5-[(oxan-4-yl)amino]pyridin-3-yl}ethenyl]-N-[(1S,2S)-2-hydroxycyclohexyl]benzamide	IC50	5.1 nM	US-12509424: Compound and composition as PDGF receptor kinase inhibitor
3-[([2,3’-bipyridin]-5’-yl)ethynyl]-N-[(1S,2S)-2-hydroxycyclohexyl]-4-methylbenzamide	IC50	5.4 nM	US-12509424: Compound and composition as PDGF receptor kinase inhibitor
2-(cyclopropylamino)-N-(5-{[(1S,2S)-2-hydroxycyclohexyl]carbamoyl}-2-methylphenyl)-1,3-thiazole-5-carboxamide	IC50	5.9 nM	US-12509424: Compound and composition as PDGF receptor kinase inhibitor
3-[(Z)-2-fluoro-2-(imidazo[1,2-b]pyridazin-3-yl)ethenyl]-N-[(1S,2S)-2-hydroxycyclohexyl]-4-methylbenzamide	IC50	5.9 nM	US-12509424: Compound and composition as PDGF receptor kinase inhibitor
2-[(cyclopropylmethyl)amino]-N-(5-{[(1S,2S)-2-hydroxycyclohexyl]carbamoyl}-2-methylphenyl)-1,3-thiazole-5-carboxamide	IC50	6 nM	US-12509424: Compound and composition as PDGF receptor kinase inhibitor
N-(5-{[(1S,2S)-2-hydroxycyclohexyl]carbamoyl}-2-methylphenyl)-2-phenyl-1,3-oxazole-5-carboxamide	IC50	6.1 nM	US-12509424: Compound and composition as PDGF receptor kinase inhibitor
N-[(1S,2S)-2-hydroxycyclohexyl]-4-methyl-3-{[5-(pyrimidin-2-yl)pyridin-3-yl]ethynyl}benzamide	IC50	6.5 nM	US-12509424: Compound and composition as PDGF receptor kinase inhibitor
3-[(Z)-2-(5-{[2-(dimethylamino)ethyl]amino}pyridin-3-yl)-2-fluoroethenyl]-N-[(1S,2S)-2-hydroxycyclohexyl]-4-methylbenzamide	IC50	7.2 nM	US-12509424: Compound and composition as PDGF receptor kinase inhibitor
N-(5-{[(1S,2S)-2-hydroxycyclohexyl]carbamoyl}-2-methylphenyl)-2-[(propan-2-yl)amino]-1,3-thiazole-5-carboxamide	IC50	8.3 nM	US-12509424: Compound and composition as PDGF receptor kinase inhibitor
2-[4-[(3-ethylphenyl)carbamoylamino]phenyl]indole-1-carboxamide	IC50	10 nM	US-9353093: Indole-1-carboxamides as kinase inhibitors
methyl 1-carbamoyl-2-[4-[(3-methylphenyl)carbamoylamino]phenyl]indole-6-carboxylate	IC50	10 nM	US-9353093: Indole-1-carboxamides as kinase inhibitors
3-({6-[(cyclopropylmethyl)amino]pyrazin-2-yl}ethynyl)-N-[(1S,2S)-2-hydroxycyclohexyl]-4-methylbenzamide	IC50	10 nM	US-12509424: Compound and composition as PDGF receptor kinase inhibitor
2-[4-[(4-methylphenyl)carbamoylamino]phenyl]indole-1-carboxamide	IC50	11 nM	US-9353093: Indole-1-carboxamides as kinase inhibitors
5-[(E)-2-cyclopropylethenyl]-N-(5-{[(1S,2S)-2-hydroxycyclohexyl]carbamoyl}-2-methylphenyl)pyridine-3-carboxamide	IC50	11 nM	US-12509424: Compound and composition as PDGF receptor kinase inhibitor
2-[4-[(3-methoxyphenyl)carbamoylamino]phenyl]indole-1-carboxamide	IC50	12 nM	US-9353093: Indole-1-carboxamides as kinase inhibitors
N-(5-{[(1S)-2-hydroxy-1-phenylethyl]carbamoyl}-2-methylphenyl)-5-phenylpyridine-3-carboxamide	IC50	12 nM	US-12509424: Compound and composition as PDGF receptor kinase inhibitor
N-(5-{[(1S,2S)-2-hydroxycyclohexyl]carbamoyl}-2-methylphenyl)-5-[(1-methylcyclopropyl)methoxy]pyridine-3-carboxamide	IC50	12 nM	US-12509424: Compound and composition as PDGF receptor kinase inhibitor
4-chloro-N-[(1S,2S)-2-hydroxycyclohexyl]-3-[(5-phenylpyridin-3-yl)ethynyl]benzamide	IC50	12 nM	US-12509424: Compound and composition as PDGF receptor kinase inhibitor
5-(4-fluorophenyl)-N-(5-{[(1S,2S)-2-hydroxycyclohexyl]carbamoyl}-2-methylphenyl)pyridine-3-carboxamide	IC50	13 nM	US-12509424: Compound and composition as PDGF receptor kinase inhibitor
5-(3-fluorophenyl)-N-(5-{[(1S,2S)-2-hydroxycyclohexyl]carbamoyl}-2-methylphenyl)pyridine-3-carboxamide	IC50	13 nM	US-12509424: Compound and composition as PDGF receptor kinase inhibitor
3-({[5-(4-aminophenyl)pyridin-3-yl]methyl}amino)-N-[(1S,2S)-2-hydroxycyclohexyl]-4-methylbenzamide	IC50	13 nM	US-12509424: Compound and composition as PDGF receptor kinase inhibitor
2-[4-[(3-methylphenyl)carbamoylamino]phenyl]indole-1-carboxamide	IC50	14 nM	US-9353093: Indole-1-carboxamides as kinase inhibitors
N-(5-{[(1S,2S)-2-hydroxycyclohexyl]carbamoyl}-2-methylphenyl)-5-[3-(trifluoromethyl)phenyl]pyridine-3-carboxamide	IC50	14 nM	US-12509424: Compound and composition as PDGF receptor kinase inhibitor
5-{(Z)-2-[5-(cyclopropylmethoxy)pyridin-3-yl]-2-fluoroethenyl}-N-[(1S,2S)-2-hydroxycyclohexyl]-6-methylpyridine-3-carboxamide	IC50	14 nM	US-12509424: Compound and composition as PDGF receptor kinase inhibitor
N-(5-{[(1S,2S)-2-hydroxycyclohexyl]carbamoyl}-2-methylphenyl)imidazo[2,1-b][1,3]thiazole-5-carboxamide	IC50	15 nM	US-12509424: Compound and composition as PDGF receptor kinase inhibitor
N-[(1S,2S)-2-hydroxycyclohexyl]-4-methyl-3-{[5-(pyrazin-2-yl)pyridin-3-yl]ethynyl}benzamide	IC50	15 nM	US-12509424: Compound and composition as PDGF receptor kinase inhibitor
N-[(1S,2S)-2-hydroxycyclohexyl]-4-methyl-3-[(6-phenylpyrazin-2-yl)ethynyl]benzamide	IC50	15 nM	US-12509424: Compound and composition as PDGF receptor kinase inhibitor
3-[(Z)-2-([2,3’-bipyridin]-5’-yl)-2-fluoroethenyl]-4-fluoro-N-[(1S,2S)-2-hydroxycyclohexyl]benzamide	IC50	15 nM	US-12509424: Compound and composition as PDGF receptor kinase inhibitor
2-[4-[(3-propan-2-ylphenyl)carbamoylamino]phenyl]indole-1-carboxamide	IC50	16 nM	US-9353093: Indole-1-carboxamides as kinase inhibitors
N-[(1S,2S)-2-hydroxycyclohexyl]-3-{[(6-{[(1r,3r)-3-methoxycyclobutane-1-carbonyl]amino}pyridin-3-yl)methyl]amino}-4-methylbenzamide	IC50	16 nM	US-12509424: Compound and composition as PDGF receptor kinase inhibitor
3-{[([2,3’-bipyridin]-5’-yl)amino]methyl}-N-[(1S,2S)-2-hydroxycyclohexyl]-4-methylbenzamide	IC50	16 nM	US-12509424: Compound and composition as PDGF receptor kinase inhibitor
N-[4-fluoro-3-({[5-(pyrimidin-2-yl)pyridin-3-yl]amino}methyl)phenyl]-N’-[(1R,2S)-2-hydroxycyclohexyl]urea	IC50	16 nM	US-12509424: Compound and composition as PDGF receptor kinase inhibitor
5-[(Z)-2-([2,3’-bipyridin]-5’-yl)-2-fluoroethenyl]-N-[(1S,2S)-2-hydroxycyclohexyl]-6-methylpyridine-3-carboxamide	IC50	16 nM	US-12509424: Compound and composition as PDGF receptor kinase inhibitor
3-[(Z)-2-fluoro-2-{5-[(4-methylpiperazin-1-yl)methyl]pyridin-3-yl}ethenyl]-N-[(1S,2S)-2-hydroxy-2,3-dihydro-1H-inden-1-yl]-4-methylbenzamide	IC50	16 nM	US-12509424: Compound and composition as PDGF receptor kinase inhibitor
5-(3-chlorophenyl)-N-(5-{[(1S,2S)-2-hydroxycyclohexyl]carbamoyl}-2-methylphenyl)pyridine-3-carboxamide	IC50	17 nM	US-12509424: Compound and composition as PDGF receptor kinase inhibitor
N-[(1S,2S)-2-hydroxycyclohexyl]-4-methyl-3-{[(6-{[(pyridin-3-yl)carbamoyl]amino}pyridin-3-yl)methyl]amino}benzamide	IC50	17 nM	US-12509424: Compound and composition as PDGF receptor kinase inhibitor
2-[4-[(3-chloro-4-fluorophenyl)carbamoylamino]phenyl]indole-1-carboxamide	IC50	19 nM	US-9353093: Indole-1-carboxamides as kinase inhibitors
5-(2-fluoro-4-methoxyphenyl)-N-(5-{[(1S,2S)-2-hydroxycyclohexyl]carbamoyl}-2-methylphenyl)pyridine-3-carboxamide	IC50	19 nM	US-12509424: Compound and composition as PDGF receptor kinase inhibitor
N-(5-{[(1S,2S)-2-hydroxycyclohexyl]carbamoyl}-2-methylphenyl)-5-[3-(trifluoromethoxy)phenyl]pyridine-3-carboxamide	IC50	19 nM	US-12509424: Compound and composition as PDGF receptor kinase inhibitor
N-[(1S,2S)-2-hydroxycyclohexyl]-4-methyl-3-{[(1S)-1-(5-phenylpyridin-3-yl)ethyl]amino}benzamide	IC50	19 nM	US-12509424: Compound and composition as PDGF receptor kinase inhibitor
5-[(Z)-2-fluoro-2-{5-[(oxetan-3-yl)amino]pyridin-3-yl}ethenyl]-N-[(1S,2S)-2-hydroxycyclohexyl]-6-methylpyridine-3-carboxamide	IC50	19 nM	US-12509424: Compound and composition as PDGF receptor kinase inhibitor
2-[4-[(2-fluoro-5-methylphenyl)carbamoylamino]phenyl]indole-1-carboxamide	IC50	20 nM	US-9353093: Indole-1-carboxamides as kinase inhibitors
3-{[6-(3-fluorophenyl)pyrazin-2-yl]ethynyl}-N-[(1S,2S)-2-hydroxycyclohexyl]-4-methylbenzamide	IC50	20 nM	US-12509424: Compound and composition as PDGF receptor kinase inhibitor
3-[({6-[(cyclopropanecarbonyl)amino]pyridin-3-yl}methyl)amino]-N-[(1S,2S)-2-hydroxycyclohexyl]-4-methylbenzamide	IC50	20 nM	US-12509424: Compound and composition as PDGF receptor kinase inhibitor
3-[(Z)-2-(2-amino-4-methylpyrimidin-5-yl)-2-fluoroethenyl]-4-fluoro-N-[(1S,2S)-2-hydroxycyclohexyl]benzamide	IC50	21 nM	US-12509424: Compound and composition as PDGF receptor kinase inhibitor

CTD chemical–gene interactions

142 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Resveratrol	increases chemical synthesis, increases phosphorylation, increases activity, decreases activity, increases expression (+5 more)	5
Estradiol	decreases expression, increases reaction, affects cotreatment, affects binding, decreases secretion (+1 more)	5
Benzo(a)pyrene	increases expression, increases secretion, affects methylation, decreases methylation	4
Lipopolysaccharides	increases secretion, decreases reaction, affects cotreatment, increases expression, increases reaction	4
6,7-dimethoxy-2-phenylquinoxaline	decreases reaction, increases expression, increases secretion, increases phosphorylation, affects binding (+1 more)	3
Phenytoin	increases expression	3
Cyclosporine	affects binding, decreases reaction, increases expression, affects cotreatment, decreases expression	3
Particulate Matter	decreases expression, increases abundance, affects binding, decreases reaction	3
lipoxin A4	affects reaction, increases phosphorylation, decreases phosphorylation, increases reaction	2
mercuric bromide	affects cotreatment, increases expression	2
2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one	decreases reaction, increases activity, increases phosphorylation, affects binding, decreases response to substance (+1 more)	2
SB 203580	decreases reaction, increases secretion, affects binding, decreases response to substance, affects cotreatment	2
U 0126	increases phosphorylation, increases reaction, affects binding, decreases response to substance, decreases reaction (+1 more)	2
Vehicle Emissions	decreases reaction, increases secretion, affects binding	2
Mevalonic Acid	affects cotreatment, decreases reaction, increases secretion, decreases activity	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Progesterone	affects cotreatment, decreases expression	2
Tetradecanoylphorbol Acetate	increases expression, decreases reaction	2
Reactive Oxygen Species	affects binding, decreases reaction, increases abundance	2
Cadmium Chloride	decreases reaction, increases abundance, decreases expression	2
Simvastatin	affects cotreatment, decreases reaction, increases expression, increases secretion, decreases activity	2
aristolochic acid I	increases expression	1
ON123300	affects binding, affects reaction, increases phosphorylation, decreases reaction	1
ammonium 2,3,3,3-tetrafluoro-2-(heptafluoropropoxy)-propanoate	affects cotreatment, affects expression	1
aminomethylphosphonic acid (AMPA)	increases expression	1
TL8-506	affects cotreatment, increases expression	1
geranylgeranyl pyrophosphate	affects cotreatment, decreases reaction, increases expression, increases secretion	1
taxifolin	decreases expression	1
bufotalin	decreases reaction, increases expression	1
methylmercuric chloride	increases expression	1

ChEMBL screening assays

3 unique, capped per target: 3 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4398804	Binding	Inhibition of PDGFRbeta (unknown origin) at 100 nM relative to control	Discovery of Potent and Noncovalent Reversible EGFR Kinase Inhibitors of EGFRL858R/T790M/C797S. — ACS Med Chem Lett

Cellosaurus cell lines

11 cell lines: 8 cancer cell line, 3 transformed cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_0F39	SV7tert PDGF	Transformed cell line	Female
CVCL_0F40	SV7tert PDGFtu2	Transformed cell line	Female
CVCL_B8M8	Abcam HCT 116 PDGFB KO	Cancer cell line	Male
CVCL_B9A3	Abcam MCF-7 PDGFB KO	Cancer cell line	Female
CVCL_B9PF	Abcam A-549 PDGFB KO	Cancer cell line	Male
CVCL_C573	SV7tert PDGFtu1	Transformed cell line	Female
CVCL_D4A8	MDFSP-S1	Cancer cell line	Female
CVCL_D4ZK	NCC-DFSP5-C1	Cancer cell line	Male
CVCL_UR53	NCC-DFSP1-C1	Cancer cell line	Male
CVCL_UR54	NCC-DFSP2-C1	Cancer cell line	Female

Clinical trials (associated diseases)

140 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT04081701	PHASE4	RECRUITING	68-Ga DOTATATE PET/MRI in the Diagnosis and Management of Somatostatin Receptor Positive CNS Tumors.
NCT04386642	PHASE4	UNKNOWN	Tranexamic Acid Reduce Blood Loss in Meningioma Resection
NCT06377371	PHASE4	RECRUITING	Feasibility of Intraoperative Tracing of Meningioma Using [Cu64]DOTATATE
NCT00517959	PHASE3	UNKNOWN	SCRT Versus Conventional RT in Children and Young Adults With Low Grade and Benign Brain Tumors
NCT01655927	PHASE3	UNKNOWN	Efficacy of Tranexamic Acid in Brain Tumor Resections
NCT03015701	PHASE3	COMPLETED	S9005 Mifepristone in Meningioma
NCT03558516	PHASE3	COMPLETED	Magnesium and Intraoperative Blood Loss in Meningioma Surgery
NCT04305470	PHASE3	COMPLETED	Gleolan for Visualization of Newly Diagnosed or Recurrent Meningioma
NCT00346164	PHASE3	COMPLETED	Observation, Radiation Therapy, Combination Chemotherapy, and/or Surgery in Treating Young Patients With Soft Tissue Sarcoma
NCT00003483	PHASE2	TERMINATED	Antineoplaston Therapy in Treating Patients With Meningioma
NCT00589784	PHASE2	COMPLETED	Phase II Trial of Sunitinib (SU011248) in Patients With Recurrent or Inoperable Meningioma
NCT00706810	PHASE2	COMPLETED	Combination of Hydroxyurea and Verapamil for Refractory Meningiomas
NCT00859040	PHASE2	COMPLETED	Monthly SOM230C for Recurrent or Progressive Meningioma
NCT01967823	PHASE2	COMPLETED	T Cell Receptor Immunotherapy Targeting NY-ESO-1 for Patients With NY-ESO-1 Expressing Cancer
NCT02523014	PHASE2	RECRUITING	Vismodegib, FAK Inhibitor GSK2256098, Capivasertib, and Abemaciclib in Treating Patients With Progressive Meningiomas
NCT02648997	PHASE2	ACTIVE_NOT_RECRUITING	An Open-Label Phase II Study of Nivolumab or Nivolumab/Ipilimumab in Adult Participants With Progessive/ Recurrent Meningioma
NCT02831257	PHASE2	COMPLETED	AZD2014 In NF2 Patients With Progressive or Symptomatic Meningiomas
NCT02847559	PHASE2	RECRUITING	Optune Delivered Electric Field Therapy and Bevacizumab in Treating Patients With Recurrent or Progressive Grade 2 or 3 Meningioma
NCT03013387	PHASE2	WITHDRAWN	Dosimetry Guided PRRT With 90Y-DOTATOC
NCT03071874	PHASE2	UNKNOWN	Vistusertib (AZD2014) For Recurrent Grade II-III Meningiomas
NCT03095248	PHASE2	TERMINATED	Trial of Selumetinib in Patients With Neurofibromatosis Type II Related Tumors
NCT03273712	PHASE2	COMPLETED	Dosimetry-Guided, Peptide Receptor Radiotherapy (PRRT) With 90Y-DOTA- tyr3-Octreotide (90Y-DOTATOC)
NCT03971461	PHASE2	ACTIVE_NOT_RECRUITING	Phase II Study of 177Lu-DOTATATE Radionuclide in Adults With Progressive or High-risk Meningioma
NCT04082520	PHASE2	RECRUITING	Lutathera for the Treatment of Inoperable, Progressive Meningioma After External Beam Radiation Therapy
NCT04298541	PHASE2	NOT_YET_RECRUITING	Direct Comparison of Ga-68-DOTATATE and Ga-68-DOTATOC
NCT04374305	PHASE2	RECRUITING	Innovative Trial for Understanding the Impact of Targeted Therapies in NF2-Related Schwannomatosis (INTUITT-NF2)
NCT04659811	PHASE2	ACTIVE_NOT_RECRUITING	Stereotactic Radiosurgery and Immunotherapy (Pembrolizumab) for the Treatment of Recurrent Meningioma
NCT05425004	PHASE2	RECRUITING	Cabozantinib for Patients With Recurrent or Progressive Meningioma
NCT05940493	PHASE2	RECRUITING	Abemaciclib in Newly Diagnosed Meningioma Patients
NCT06012929	PHASE2	WITHDRAWN	A Study of ONC201 for Refractory Meningioma
NCT06126588	PHASE2	RECRUITING	Combination of Everolimus and 177Lu-DOTATATE in the Treatment of Grades 2 and 3 Refractory Meningioma: a Phase IIb Clinical Trial
NCT06132685	PHASE2	RECRUITING	Post-Operative Dosing of Dexamethasone in Patients With Brain Tumors After a Craniotomy, PODS Trial
NCT06322342	PHASE2	COMPLETED	Phase 2 Ascending Dose Safety and Efficacy Study of RVP-001, a Manganese-based MRI Contrast Agent
NCT06326190	PHASE2	RECRUITING	177Lu-DOTATATE for Recurrent Meningioma
NCT06439420	PHASE2	COMPLETED	CBT-I in Primary Brain Tumor Patients: Phase IIc Randomized Feasibility Pilot Trial
NCT06684795	PHASE2	RECRUITING	FG001 in Subjects with Meningiomas or Presumed Low-Grade Gliomas Scheduled for Neurosurgery
NCT06710249	PHASE2	RECRUITING	Impact of Salovum® and SPC® Flakes on Brain Tumor Induced Edema
NCT06804655	PHASE2	NOT_YET_RECRUITING	Pharmacoscopy for Patients With Refractory Primary Brain Tumors
NCT07428616	PHASE2	RECRUITING	A Study of Zanzalintinib in Participants With Recurrent or Progressive Meningioma
NCT07533942	PHASE2	NOT_YET_RECRUITING	A Study of JZP3507 (ONC206) in Recurrent Grade 2 or 3 Meningioma