Sitravatinib (MGCD516) is an inhibitor targeting multiple RTKs involved in driving sarcoma cell growth, including c-Met, c-Kit, PDGFRα/β, PDGFR, and Axl.

EphA3:1 nM, DDR2:0.5 nM, Mer:2 nM, Axl:1.5 nM, VEGFR3/FLT4:2 nM

MGCD516 (Sitravatinib) 是一种针对紧密相关RTKs谱系的抑制剂，包括RET、分裂型RTKs（PDGFR、VEGFR和KIT）、DDR2、TRK家族、MET和AXL。MGCD516显著阻断潜在驱动RTKs的磷酸化作用，并在体外实验中引发强大的抗增殖效果。

Sitravatinib在含有Sitravatinib靶点遗传变化的非临床癌症模型中展示了抗肿瘤活性，包括NTRK重排、RET重排或CHR4q12扩增。在活体内肿瘤异种移植模型中，MGCD516显著抑制了肿瘤生长。与两种已广泛研究、靶点特异性重叠的多激酶抑制剂imatinib和crizotinib相比，MGCD516在体外及体内的疗效更为卓越。

Cell lines: DDLS,LS141,and MPNST. Concentrations: 62.5,125,250,500,1000,2000 nM2,000-3,000 cells were plated in 96-well plates in RPMI/DME media with 10% FBS and then treated with the indicated drugs the next day.After 72 hours,media was replaced with 100 μL of media with 10% serum and 10% CCK-8 solution.After 1 hour,the optical density was read at 450 nm to determine viability.Background values from negative control wells without cells were subtracted for final sample quantification.Data was plotted as % cell viability compared to DMSO control.

Animal Models: ICR/SCID mice. Formulation: 0.5% hydroxypropyl methylcellulose (HPMC) and 0.1% Tween-80 solution (pH 1.4). Dosages: 15 mg/kg. Administration: p.o.