Dasatinib D8

Dasatinib-d₈ is intended for use as an internal standard for the quantification of dasatinib by GC- or LC-MS. Dasatinib is a potent inhibitor of the non-receptor tyrosine kinases Abl and Src as well as other members of the Src family.^1,2 It is effective at sub-nanomolar concentrations, inhibiting Src, Abl, and Lck with IC₅₀ values of 0.05, 0.5, and 0.4 nM, respectively.^1,3,4 At nanomolar concentrations, dasatinib also blocks the activity of several other receptor and non-receptor tyrosine kinases, plus drug-resistant mutants.^3,4 Because of these activities, dasatinib has potential therapeutic value in diseases characterized by elevated levels of these kinases, including some forms of cancer and fibrotic disease.^1,5,6,7

1.Lombardo, L.J., Lee, F.Y., Chen, P., et al.Discovery of N-(2-chloro-6-methyl-phenyl)-2-(6-(4-(2-hydroxyethyl)-piperazin-1-yl)-2-methylpyrimidin-4-ylamino)thiazole-5-carboxamide (BMS-354825),a dual Src/Abl kinase inhibitor with potent antitumor activity in preclinical assaysJ. Med. Chem.47(27)6658-6661(2004) 2.Das, J., Chen, P., Norris, D., et al.2-aminothiazole as a novel kinase inhibitor template. Structure-activity relationship studies toward the discovery of N-(2-chloro-6-methylphenyl)-2-[[6-[4-(2-hydroxyethyl)-1-piperazinyl)]-2-methyl-4-pyrimidinyl]amino)]-1,3-thiazole-5-carboxamide (Dasatinib, BMS-354825) as a potent pan-Src kinase inhibitorJ. Med. Chem.49(23)6819-6823(2006) 3.Davis, M.I., Hunt, J.P., Herrgard, S., et al.Comprehensive analysis of kinase inhibitor selectivityNat. Biotechnol.29(11)1046-1051(2011) 4.Carter, T.A., Wodicka, L.M., Shah, N.P., et al.Inhibition of drug-resistant mutants of ABL, KIT, and EGF receptor kinasesProc. Natl. Acad. Sci. USA102(31)11011-11016(2005) 5.El-Amm, J., Freeman, A., Patel, N., et al.Bone-targeted therapies in metastatic castration-resistant prostate cancer: Evolving paradigmsProstate Cancer20131-10(2013) 6.Distler, J.H.W., and Distler, O.Intracellular tyrosine kinases as novel targets for anti-fibrotic therapy in systemic sclerosisRheumatology47(Suppl 5)10-11(2008) 7.McFarland, K.L., and Wetzstein, G.A.Chronic myeloid leukemia therapy: Focus on second-generation tyrosine kinase inhibitorsCancer Control16(2)132-140(2009)