Dasatinib’s mechanism of action

Dasatinib is indicated for the treatment of adult patients with newly diagnosed Philadelphia chromosome-positive chronic myelogenous leukemia (Ph+) (CML) in the chronic phase. For the treatment of adults with chronic, accelerated, or myeloid or lymphoblastic stagePh+ CMLwho are resistant or intolerant to prior therapy, including imatinib. For the treatment of adults with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) who are resistant or intolerant to prior therapy.

Dasatinib inhibits the following kinases: BCR-ABL, SRC family (SRC, LCK, Yes, FYN), c-KIT, EPHA2 and PDGFRβ. Based on modeling studies, dasatinib is expected to bind to multiple conformations of ABL kinase. In vitro, dasatinib is active in leukemia cell lines representing imatinib mesylate-sensitive and -resistant disease variants. Dasatinib inhibits the growth of chronic myelogenous leukemia (CML) and acute lymphoblastic leukemia (ALL) cell lines that overexpress BCR-ABL. Under experimental conditions, dasatinib can overcome imatinib resistance caused by mutations in the BCR-ABL kinase domain, activation of alternative signaling pathways involving SRC family kinases (LYN, HCK), and overexpression of multidrug resistance genes.

Dasatinib is mainly metabolized in the human body viaCYP3A4. CYP3A4 is the main enzyme responsible for the formation of active metabolites. Flavin-containing monooxygenase 3 (FMO-3) and uridine diphosphate glucuronosyltransferase (UGT) are also involved in the formation of dasatinib metabolites. Exposure to an active metabolite equivalent to dasatinib is approximately 5% of the AUC of dasatinib. The active metabolite of dasatinib is unlikely to play a major role in the observed pharmacology of this drug. Dasatinib also has several other inactive oxidative metabolites. If you want to get more high-quality information, you can contact Yaode, and Yaode will do its best to learn more about high-quality overseas drugs for you.