1009333-61-2

Upstream product

• 1009333-67-8 ethyl 3-(4-trimethylsilyl-2-fluoro-phenylamino)-furo[3,2-c]pyridine-2-carboxylate 
• 1009333-55-4 ethyl 3-(trifluoromethanesulfonyloxy)-furo[3,2-c]pyridine-2-carboxylate 
• 119293-22-0 ethyl 3-hydroxyfuro<3,2-c>pyridine-2-carboxylate 
• 37831-62-2 ethyl 4-chloronicotinate 

Downstream Products

• 1009335-01-6 C₁₄H₈FIN₂O₃ 

Relevant academic research and scientific papers

Bcl-2/Bcl-xL inhibition increases the efficacy of MEK inhibition alone and in combination with PI3 kinase inhibition in lung and pancreatic tumor models

Although mitogen-activated protein (MAP)-extracellular signal-regulated kinase (ERK) kinase (MEK) inhibition is predicted to cause cell death by stabilization of the proapoptotic BH3-only protein BIM, the induction of apoptosis is often modest. To determine if addition of a Bcl-2 family inhibitor could increase the efficacy of a MEK inhibitor, we evaluated a panel of 53 non-small cell lung cancer and pancreatic cancer cell lines with the combination of navitoclax (ABT-263), a Bcl-2/Bcl-xL (BCL2/BCL2L1) antagonist, and a novel MAP kinase (MEK) inhibitor, G-963. The combination is synergistic in the majority of lines, with an enrichment of cell lines harboring KRAS mutations in the high synergy group. Cells exposed to G-963 arrest in G1 and a small fraction undergo apoptosis. The addition of navitoclax to G-963 does not alter the kinetics of cell-cycle arrest, but greatly increases the percentage of cells that undergo apoptosis. The G-963/navitoclax combination was more effective than either single agent in the KRAS mutant H2122 xenograft model; BIM stabilization and PARP cleavage were observed in tumors, consistent with the mechanism of action observed in cell culture. Addition of the phosphatidylinositol 3-kinase (PI3K, PIK3CA) inhibitor GDC-0941 to this treatment combination increases cell killing compared with double- or single-agent treatment. Taken together, these data suggest the efficacy of agents that target the MAPK and PI3K pathways can be improved by combination with a Bcl-2 family inhibitor.

AZA-BENZOFURANYL COMPOUNDS AND METHODS OF USE

The invention relates to azabenzofuranyl compounds of Formula (I) with anti-cancer and/or anti-inflammatory activity and more specifically to azabenzofuranyl compounds which inhibit MEK kinase activity. The invention provides compositions and methods useful for inhibiting abnormal cell growth or treating a hyperproliferative disorder, or treating an inflammatory disease in a mammal. The invention also relates to methods of using the compounds for in vitro, in situ, and in vivo diagnosis or treatment of mammalian cells, or associated pathological conditions.