GZD824 (HQP1351) 是一种高效的，具有口服活性的 pan-Bcr-Abl 抑制剂。GZD824 能广泛而有效地抑制突变型 Bcr-Abl。GZD824 对天然的 Bcr-Abl 和 Bcr-AblT315I 作用的 IC50 值分别为 0.34 nM 和 0.68 nM。GZD824 具有抗肿瘤作用。
货号:ajcx33266
CAS:1257628-77-5
分子式:C29H27F3N6O
分子量：532.56
溶解度:DMSO : ≥ 100 mg/mL (187.77 mM)
纯度：98%
存储：Store at -20°C
库存：现货

Background:

GZD824 (HQP1351) is a potent and orally active pan-Bcr-Abl inhibitor. GZD824 potently inhibits a broad spectrum of Bcr-Abl mutants. GZD824 strongly inhibits native Bcr-Abl and Bcr-AblT315I with IC50s of 0.34 nM and 0.68 nM, respectively. GZD824 has antitumor activity[1].

GZD824 shows antiproliferative activity in stably transformed Ba/F3 cells whose growth was driven by native Bcr-Abl or Bcr-Abl mutants[1].GZD824 selectively and potently inhibits the proliferation of Bcr-Abl-positive leukemia cells[1].GZD824 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-AblT315I(0.1-100 nM; 4.0 hours)[1].

GZD824 suppresses tumor growth in mice bearing allografted Ba/F3 cells expressing Bcr-Abl WT[1].GZD824 (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-AblT315I[1].GZD824 exhibits a good oral bioavailability (rat 48.7%) and Cmax (rat 390.5 μg/L) following oral administration (rat; 25 mg/kg)[1].GZD824 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].

[1]. Ren X, Pan X, Zhang Z, Identification of GZD824 as an orally bioavailable inhibitor that targets phosphorylated and nonphosphorylated breakpoint cluster region-Abelson (Bcr-Abl) kinase and overcomes clinically acquired mutation-induced resistance against imatinib. J Med Chem. 2013 Feb 14;56(3):879-94.