(Z)-Orantinib ((Z)-SU6668) is a potent, selective, orally active, and ATP-competitive inhibitor of Flk-1/KDR, PDGFRβ, and FGFR1, with IC50 values of 2.1, 0.008, and 1.2 μM, respectively. (Z)-Orantinib is an effective antiangiogenic and antitumor agent that induces established tumor regression [1] [2].

SU6668 rapidly inhibits Flk-1 trans-phosphorylation (K i =2.1 μM), FGFR1 trans-phosphorylation (K i =1.2 μM), and PDGFR autophosphorylation (K i =0.008 μM) within 5-15 minutes, as well as the VEGF-induced increase in KDR tyrosine phosphorylation in HUVECs at concentrations between 0.03-10 μM after 60 minutes [1]. Additionally, it dose-dependently suppresses HUVEC mitogenesis triggered by VEGF and FGF, with IC 50 values of 0.34 μM and 9.6 μM, respectively [1].

SU6668, administered orally (p.o.) at dosages ranging from 4 to 200 mg/kg/day for 21 days, demonstrates a dose-dependent suppression of A431 tumor growth in athymic mice, with the most significant growth inhibition observed at 200 mg/kg/day, achieving a 97% reduction without any mortality across treatment groups. When administered intraperitoneally (i.p.) at 75 mg/kg/day for 22 days, SU6668 markedly inhibits tumor angiogenesis and vascularization. Additionally, oral administration of SU6668 at 200 mg/kg/day for durations between 11 to 27 days results in the significant regression of large established A431 xenografts. The study involved female athymic mice (BALB/c, nu/nu) implanted with A431 tumor cells.