JNJ38877605 是 ATP竞争性 c-Met 抑制剂 (IC50:4 nM),对c-Met的抑制性比对其它 200 种酪氨酸和丝氨酸-苏氨酸激酶的抑制性高 600 倍。
产品描述
JNJ-38877605 is an ATP-competitive c-Met inhibitor (IC50: 4 nM), 600-fold selective for c-Met than 200 other tyrosine and serine-threonine kinases.
体外活性
JNJ-38877605 shows more than 600-fold selectivity for c-Met compared with more than 200 other diverse tyrosine and serine-threonine kinases and also potently inhibits HGF-stimulated and constitutively activated c-Met phosphorylation in vitro. In EBC1, GTL16, NCI-H1993, and MKN45 cells, JNJ-38877605 (500 nM) leads to a significant reduction of phosphorylation of Met and RON, another key player in invasive growth. A recent study shows that JNJ-38877605 is involved in modulating secretion of IL-8, GROa, uPAR and IL-6 in GTL16 cells.
体内活性
In mice bearing established GTL16 xenografts, JNJ-38877605 (40 mg/kg/day, p.o., total 3day) results in a statistically marked decrease in the plasma levels of human IL-8 (0.150-0.050 ng/mL) and GROα (0.080-0.030 ng/mL). While concentrations of uPAR in the blood become reduced to more than 50% at the same dose.
动物实验
Animal Models: GTL16 cells are inoculated subcutaneously into the right posterior flank (or both right and left posterior flanks,for determination of uPAR and IL-6) of 6-week-old immuno-deficient nu/nu female mice on Swiss CD1 background. Formulation: JNJ-38877605 is dissolved in PBS. Dosages: ≤40 mg/kg/day. Administration: Administered via p.o.
Cas No.
943540-75-8
分子式
C19H13F2N7
分子量
377.359
储存和溶解度
DMSO:35 mg/mL (92.8 mM)
H2O:<1 mgml
Ethanol:<1 mgml
Powder: -20°C for 3 years
In solvent: -80°C for 2 years