NPS-1034 is a dual Met/Axl inhibitor with IC50 of 48 nM and 10.3 nM, respectively.

Axl:10.3 nM

在HCC827/GR细胞中，NPS-1034并未显示出显著的抗增殖效果，但通过抑制MET、Akt和Erk的磷酸化作用，克服了gefitinib的抗药性。在H820细胞中，NPS-1034提高了对EGFR-TKIs的敏感性。在HCC78细胞中，NPS-1034抑制了ROS1活性和细胞增殖。此外，gefitinib和NPS-1034的联合使用通过诱导caspase-3和PARP-1的裂解，增强了细胞死亡。[1] 对于高度表达MET基因和p-MET的MKN45和SNU638细胞系，NPS-1034抑制了细胞活力，其IC50分别为112.7和190.3nM。[2]

在携带HCC827/GR肿瘤异种移植的SCID小鼠中，NPS-1034 (10 mg/kg, p.o.) 能够减缓肿瘤生长，而gefitinib和NPS-1034的联合使用能够通过抑制肿瘤增殖和诱导凋亡来增强对肿瘤生长的抑制。[1] 在携带MKN45异种移植肿瘤的裸鼠中，NPS-1034 (30 mg/kg, p.o.) 通过抑制血管生成和促进凋亡来减缓肿瘤生长。[2]

Kinase inhibition profile: The in vitro NPS-1034 profile of inhibition of RTKs is analyzed using RTK assay kits according to the manufacturer's protocols.

To perform the MTT assay, cells (0.5 × 104/well) are plated in 96-well sterile plastic plates and allowed to attach overnight. Cells are exposed to varying doses of gefitinib, erlotinib, PHA-665752, and NPS-1034 in medium containing 1% FBS. After 72 hours, 15 μL of MTT solution (5 mg/mL) is added to each well and plates are incubated for 4 hours. Crystalline formazan is solubilized with 100 μL of a 10% (w/v) SDS solution for 24 hours. Absorbance at 595 nm is read spectrophotometrically using a microplate reader.(Only for Reference)