JNJ-38877605

Administered via p.o.

6-(difluoro(6-(1-methyl-1H-pyrazol-4-yl)-[1, 2, 4]triazolo[4, 3-b]pyridazin-3-yl)methyl)quinoline

JNJ-38877605 is an ATP-competitive inhibitor of c-Met with IC50 of 4 nM.

JNJ-38877605 is dissolved in PBS.

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. [1] 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. [2] A recent study shows that JNJ-38877605 is involved in modulating secretion of IL-8, GROa, uPAR and IL-6 in GTL16 cells. [3]

377, 35

Data from [PLoS Biol , 2011, 9, e1001162 ], JNJ-38877605purchased from Selleck, Inducers of EMT. (A) Expression of Hgf, Egf, and Tgfb1 genes in RETAAD tumors analyzed by qRT-PCR. Hgf and Tgfb1 are preferentially expressed in PMN-MDSC, while Egf is preferentially expressed in tumor cells. Data are from four individual experiments using sorted fractions of PMNMDSC and melanoma cells. Bars represent mean 6 SD. (B) NBT-II cells (100 cells per well) were plated for 4 d to allow for colony growth and were pretreated for 24 h with inhibitors before the addition of PMN-MDSC. After co-culture with PMN-MDSCs in the presence of inhibitors, cells were fixed and stained with anti-rat desmoplakin. Green, Desmoplakin, red, H2b (nuclear stain). PD153035-EGFR inhibitor, JNJ38877605-c-met (HGFR) inhibitor, and SB525334-TGF-bR1 inhibitor. Images are representative of three independent experiments.

DMSO 15 mg/mL, Water <1 mg/mL, Ethanol <1 mg/mL