Olverembatinib (dimesylate)

Olverembatinib (GZD824) dimesylate is a potent and orally active pan-Bcr-Abl inhibitor. Olverembatinib dimesylate potently inhibits a broad spectrum of Bcr-Abl mutants. Olverembatinib dimesylate strongly inhibits native Bcr-Abl and Bcr-Abl^T315I with IC₅₀s of 0.34 nM and 0.68 nM, respectively. Olverembatinib dimesylate has antitumor activity^[1]. Olverembatinib (dimesylate) is a click chemistry reagent, itcontains an Alkyne group and can undergo copper-catalyzed azide-alkyne cycloaddition (CuAAc) with molecules containing Azide groups. IC50 & Target:IC50: 0.68 nM (Bcr-Abl^T315I), 0.27 nM (Bcr-Abl^E255K) , 0.71 nM (Bcr-Abl^G250E) , 0.15 nM (Bcr-Abl^Q252H), 0.35 nM (Bcr-Abl ^H396P), 0.29 nM (Bcr-Abl ^M351T), 0.35 nM (Bcr-Abl^Y253F), Bcr-Abl^F317L[1] In Vitro: Olverembatinib dimesylate shows antiproliferative activity in stably transformed Ba/F3 cells whose growth was driven by native Bcr-Abl or Bcr-Abl mutants^[1].
Olverembatinib dimesylate selectively and potently inhibits the proliferation of Bcr-Abl-positive leukemia cells^[1].
Olverembatinib dimesylate inhibits Bcr-Abl signaling in K562 (1-20 nM; 4.0 hours) and Ba/F3 stable cell lines expressing native Bcr-Abl (0.1-100 nM; 4.0 hours) or Bcr-Abl^T315I(0.1-100 nM; 4.0 hours)^[1].
In Vivo: Olverembatinib dimesylate suppresses tumor growth in mice bearing allografted Ba/F3 cells expressing Bcr-Abl ^WT[1].
Olverembatinib dimesylate (1-20 mg/kg; i.g.; daily; for 10 days) significantly increases the median survival of the mice bearing allografted Ba/F3 cells expressing Bcr-Abl^T315I[1].
Olverembatinib dimesylate exhibits a good oral bioavailability (rat 48.7%) and C_max (rat 390.5 μg/L) following oral administration (rat; 25 mg/kg)^[1].
Olverembatinib dimesylate exhibits terminal elimination half-lives (rat 5.6 h) due to high plasma clearance (rat 1.7 L/h/kg) following intravenous administration (rat 5 mg/kg)^[1].