Is dasatinib a targeted drug? Belong to several generations

Dasatinib (Dasatinib) is an outstanding achievement developed by Bristol Myers Squibb. It belongs to the category of second-generation small molecule multi-target BCR-ABL kinase inhibitors. Compared with the first-generation drug imatinib, dasatinib exhibits more potent activity against unmutated ABL kinase in vitro.

Dasatinib was originally developed as an inhibitor of Src family kinases (such as Fyn, Yes, Src and Lyk). However, it can also effectively inhibit multiple kinases such as BCR-ABL, EphA2, platelet-derived growth factor receptor and c-Kit. In addition, dasatinib has the ability to bind to other tyrosine and serine/threonine kinases such as mitogen-activated protein kinase, receptor tyrosine kinase, and discoid domain receptor 1.

Dasatinib has shown excellent effects in inhibiting the proliferation and kinase activity of imatinib-resistant wild-type andBCR-ABL mutant cell lines, but it should be noted that cell lines carrying the T315I mutation are not sensitive to it. Data from in vivo studies further confirmed dasatinib's potency: it was 325 times more potent than imatinib and 16 times more potent than nilotinib, another BCR-ABL kinase inhibitor. In mouse models, dasatinib not only inhibited the growth of leukemia cells, but also significantly prolonged the survival of mice carrying wild-type BCR ABL and M351T mutations. However, consistent with in vivo studies, it had no significant effect on the T315I mutant.

Dasatinib, as a bispecificSrc and ABL inhibitor, can simultaneously inhibit the active and inactive conformations of ABL. This feature makes it have wider application prospects in drug treatment. In view of the excellent efficacy and broad applicability of dasatinib, the U.S. Food and Drug Administration (FDA) has approved it for the treatment of chronic phase, accelerated phase or blast phase chronic myeloid leukemia that is resistant or intolerant to imatinib, as well as Ph chromosome-positive acute lymphoblastic leukemia that is resistant to or intolerant to previous treatments.