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Research Area
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Description
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Cancer |
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Biological Activity
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Description
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JNJ-38877605 is an ATP-competitive inhibitor of c-Met with IC50 of 4 nM. |
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Targets
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c-Met |
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IC50 |
4 nM [1] |
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In Vitro
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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] |
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In Vivo
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In mice bearing established GTL16 xenografts, JNJ-38877605, dosed orally with 40 mg/kg/day for 72 hours, results in a statistically significant decrease in the plasma levels of human IL-8 (from 0.150 ng/mL to 0.050 ng/mL) and GROα (from 0.080 ng/mL to 0.030 ng/mL). While concentrations of uPAR in the blood become reduced to more than 50% at the same dose. [3] |
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Clinical Trials
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JNJ-38877605 is currently in Phase I clinical trials in patients with Neoplasms. |
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Features
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Protocol
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Animal Study
[3]
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| 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 immunodeficient nu/nu female mice on Swiss CD1 background. |
| Formulation |
JNJ-38877605 is dissolved in PBS. |
| Doses |
≤40 mg/kg/day |
| Administration |
Administered via p.o. |
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