Imatinib-d3 (Synonyms: Genfatinib-d3)

Imatinib-d₃ is intended for use as an internal standard for the quantification of imatinib by GC- or LC-MS. Imatinib is an inhibitor of the receptor tyrosine kinases c-Abl, Bcr-Abl, PDGFR, and c-Kit.¹ It inhibits ligand-stimulated autophosphorylation of PDGFR and c-Kit (IC₅₀s = ~0.3 and ~0.1 μM, respectively).^1,2 Imatinib inhibits the proliferation of Bcr-Abl-dependent R10(-) cells (IC₅₀s = ~35-40 nM) and HMC-1 cells expressing constitutively active c-Kit in a concentration-dependent manner.^1,3 It prolongs survival in a mouse model of chronic myeloid leukemia when administered at a dose of 100 mg/kg twice per day.⁴ Imatinib (25 and 50 µM) also inhibits the replication of Middle East respiratory syndrome coronavirus (MERS-CoV) and severe acute respiratory syndrome CoV (SARS-CoV) in Vero E6 cells.⁵ It reduces viral titers in Vero cells infected with infectious bronchitis virus (IBV), a coronavirus, when used at a concentration of 10 µM via inhibition of IBV surface glycoprotein protein-induced syncytia formation and virus-cell fusion.⁶ Formulations containing imatinib have been used in the treatment of various cancers.

1.Heinrich, M.C., Griffith, D.J., Druker, B.J., et al.Inhibition of c-kit receptor tyrosine kinase activity by STI 571, a selective tyrosine kinase inhibitorBlood96(3)925-932(2000) 2.Buchdunger, E., Zimmermann, J., Mett, H., et al.Inhibition of the Abl protein-tyrosine kinase in vitro and in vivo by a 2-phenylaminopyrimidine derivativeCancer Res.56(1)100-104(1996) 3.Wisniewski, D., Lambek, C.L., Liu, C., et al.Characterization of potent inhibitors of the Bcr-Abl and the c-kit receptor tyrosine kinasesCancer Res.62(15)4244-4255(2002) 4.Wolff, N.C., Veach, D.R., Tong, W.P., et al.PD166326, a novel tyrosine kinase inhibitor, has greater antileukemic activity than imatinib mesylate in a murine model of chronic myeloid leukemiaBlood105(10)3995-4003(2005) 5.Coleman, C.M., Sisk, J.M., Mingo, R.M., et al.Abelson kinase inhibitors are potent inhibitors of severe acute respiratory syndrome coronavirus and Middle East respiratory syndrome coronavirus fusionJ. Virol.90(19)8924-8933(2016) 6.Sisk, J.M., Frieman, M.B., and Machamer, C.E.Coronavirus S protein-induced fusion is blocked prior to hemifusion by Able kinase inhibitorsJ. Gen. Virol.99(5)619-630(2018)