Peter Kovar

TL;DR: The re-engineering of navitoclax is reported to create a highly potent, orally bioavailable and BCL-2–selective inhibitor, ABT-199, which inhibits the growth of BCL–dependent tumors in vivo and spares human platelets, indicating that selective pharmacological inhibition of Bcl-2 shows promise for the treatment of B CL-2-dependent hematological cancers.

TL;DR: BCL-XL–selective inhibitors have the potential to enhance the efficacy of docetaxel in solid tumors and avoid the exacerbation of neutropenia observed with navitoclax, and demonstrate the translational utility of this toolkit of selective BCL-2 family inhibitors.

TL;DR: This work represents the first description of small-molecule MCL-1 inhibitors with sufficient potency to induce clear on-target cellular activity, and demonstrates the utility of these molecules as chemical tools for dissecting the basic biology of M CL-1.

TL;DR: A-1155463 caused a mechanism-based and reversible thrombocytopenia in mice and inhibited H146 small cell lung cancer xenograft tumor growth in vivo following multiple doses and represents an excellent tool molecule for studying BCL-XL biology as well as a productive lead structure for further optimization.