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Chemical Structure| 1260665-84-6 Chemical Structure| 1260665-84-6

Structure of 1260665-84-6

Chemical Structure| 1260665-84-6

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Quinn A. Bumpers ; Robert W. Pipal ; Anna M. Benz-Weeden ; James T. Brewster II ; Adam Cook ; Amy L. Crooks , et al.

Abstract: Mesenchymal-epithelial transition factor (MET) is a receptor tyrosine kinase that serves a critical function in numerous developmental, morphogenic, and proliferative signaling pathways. If dysregulated, MET has been shown to be involved in the development and survival of several cancers, including non-small cell lung cancer (NSCLC), renal cancer, and other epithelial tumors. Currently, the clinical efficacy of FDA approved MET inhibitors is limited by on-target acquired resistance, dose-limiting toxicities, and less than optimal efficacy against brain metastasis. Therefore, there is still an unmet medical need for the development of MET inhibitors to address these issues. Herein we report the application of structure-based design for the discovery and development of a novel class of brain-penetrant MET inhibitors with enhanced activity against clinically relevant mutations and improved selectivity. Compound 13 with a MET D1228N cell line IC50 value of 23 nM showed good efficacy in an intracranial tumor model and increased the median overall survival of the animals to 100% when dosed orally at 100 mg/kg daily for 21 days.

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Product Details of [ 1260665-84-6 ]

CAS No. :1260665-84-6
Formula : C6H4ClN3
M.W : 153.57
SMILES Code : ClC1=NC=CN2C1=CC=N2
MDL No. :MFCD18250200
InChI Key :UPAOWFRREBXVDZ-UHFFFAOYSA-N
Pubchem ID :72213177

Safety of [ 1260665-84-6 ]

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302-H315-H319-H335
Precautionary Statements:P261-P305+P351+P338
 

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