Abstract Background: The platelet-derived growth factor (PDGF) receptors are receptor tyrosine kinases which contain two isoforms, PDGFRα and β. They form homo- or hetero-dimers and exert different biological functions including organ development and vascularization. Dysregulation of PDGF receptors has been implicated in tumor initiation and progression in addition to playing a major role in epithelial-mesenchymal transition, metastasis, and tumor angiogenesis. ARQ 087, a pan FGF receptor inhibitor inhibits FGFR1, 2, and 3 with IC50 from 2 to 4 nM. Methods: We have performed in vitro kinase profiling to determine percent inhibition of selected kinases and IC50 for PDGFRα and its mutated form. siRNA knockdown was applied to evaluate cell proliferation of the PDGFRα-dependent cancer cell lines NCI-H1703 and A-204. Western blot analysis including phospho PDGFRα/β, pSTAT3, pAKT, pERK together with cell migration and invasion analysis was performed on NCI-H1703 and NIH-3T3 cells. Results: ARQ 087 is an inhibitor of PDGF receptors which is supported by the in vitro kinase profiling results. ARQ 087 but not Imatinib, was equally potent against wild-type PDGFRα and the mutated form of PDGFRα (D842V), indicating a potential clinical implication for Imatinib-resistant PDGFR-driven cancers. Knockdown of PDGFRα using siRNA suppressed PDGFRα-dependent cancer cell line proliferative activity. ARQ 087 inhibition of cell proliferation was accompanied by the reduction of phosphorylation of PDGFRα and its downstream proteins. In addition to the anti-proliferative activity, ARQ 087 suppressed migration and invasion of NCI-H1703 cells through targeting PDGFRα and migration of NIH-3T3 cells through targeting PDGFRβ. Conclusions: ARQ 087 is not only an inhibitor of the FGFR family but also of the PDGFR family, suggesting that targeting cancers driven by PDGF receptors or mutated forms may provide an additional clinical path for ARQ 087. Citation Information: Mol Cancer Ther 2013;12(11 Suppl):B289. Citation Format: Yi Yu, Jennifer Lee, Daniel T. Dransfield. Inhibition of platelet-derived growth factor receptors by ARQ 087, a multi-tyrosine kinase inhibitor. [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2013 Oct 19-23; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2013;12(11 Suppl):Abstract nr B289.