Flumatinib (HHGV678)

Flumatinib is an inhibitor of the non-receptor tyrosine kinase Bcr-Abl (IC₅₀ = 1.2 nM).¹ It is selective for Bcr-Abl over VEGFR2, c-Src, EGFR, and HER2 at 1 ?M but does inhibit PDGFRβ and c-Kit (IC₅₀s = 307.6 and 665.5 nM, respectively). Flumatinib inhibits the proliferation of K562 chronic myelogenous leukemia (CML) cells expressing wild-type Bcr-Abl (IC₅₀ = 5.1 nM) and 32D cells expressing the Bcr-Abl mutations Bcr-Abl^Q252H, Bcr-Abl^Y253F, Bcr-Abl^E255K, Bcr-Abl^M351T, and Bcr-Abl^H396P (IC₅₀s = 76.3, 40.4, 123.2, 20.2, and 34.6 nM, respectively), which confer resistance to the c-Abl, Bcr-Abl, PDGFR, and c-Kit inhibitor imatinib . It also induces tumor regression and increases survival time in a K562 mouse xenograft model when administered at a dose of 75 mg/kg per day. Flumatinib also increases the viability of Vero E6 cells infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2; EC₅₀ = 1.6 ?M) and reduces the levels of SARS-CoV-2 in the supernatant of Vero E6 infected cells.²

1.Luo, H., Quan, H., Xie, C., et al.HH-GV-678, a novel selective inhibitor of Bcr-Abl, outperforms imatinib and effectively overrides imatinib resistanceLeukemia24(10)1807-1809(2010) 2.Singh, A., and Arkin, I.T.Targeting viral ion channels: A promising strategy to curb SARS-CoV-2Pharmaceuticals (Basel)15(4)396(2022)