GZD856

GZD856 formic is a potent and orally active PDGFRα/β inhibitor, with IC₅₀s of 68.6 and 136.6 nM, respectively. GZD856 formic is also a Bcr-Abl^T315I inhibitor, with IC₅₀s of 19.9 and 15.4 nM for native Bcr-Abl and the T315I mutant. GZD856 formic has antitumor activity^[1][2]. IC50 & Target: IC50: 68.6 nM (PDGFRα), 136.6 nM (PDGFRβ)^[1]; 19.9 nM (Bcr-Abl), 115.4 nM (T315I mutant)^[2] In Vitro: GZD856 (0.0032-10 μM, 72 h) exerts antiproliferative activity against a panel of lung cancer cells^[1].
GZD856 (0.3-3 μM; 24-28 h) induces a dose-dependent G0/G1 phase arrest and apoptosis in H1703 but not A549 cells^[1].
GZD856 (0.1-10 μM; 6 h) dose-dependently inhibits the PDGFRα/β phosphorylation and downstream signaling in H1703 and A549 cells^[1].
GZD856 inhibits the proliferation of K562, K562R (Q252H) and murine Ba/F3 cells ectopically expressing Bcr-Abl^WT and Bcr-Abl^T315I, with IC₅₀s of 2.2, 67.0, 0.64 and 10.8 nM, respectively^[2]. In Vivo: GZD856 (10-30 mg/kg, p.o. once daily for 16 d) displays good antitumor activity in both H1703 and A549 lung cancer models and is well tolerated. GZD856 inhibits brain and liver metastasis of lung cancer cells in an A549-Luc orthotopic model^[1].
GZD856 (10 mg/kg; p.o. once daily for 8 d) potently inhibits tumor growth in mouse bearing xenograft K562 and Ba/F3 cells expressing Bcr-Abl^T315I[2].
GZD856 (5 mg/kg; a single i.v.) exhibits a long half-life (T_1/2=19.97 h), optimal plasma exposure (C_max=934.38 μg/L) and a AUC_0-∞ (8165.8 μg/L h) in rats^[1].
GZD856 (25 mg/kg; a single p.o.) exhibits a long half-life (T_1/2=22.2 h), optimal plasma exposure (C_max=899.5 μg/L) and a good oral bioavailability (BA=78%) in rats^[1].