Jamal Carlos Saeh

TL;DR: Findings from a series of lung cancer patients with acquired resistance to the ALK TKI crizotinib reinforce the need to tailor therapeutic strategies to the specific underlying drug resistance mechanisms in the tumors to improve clinical outcomes.

TL;DR: The ability of molecular docking, using the program Glide and an MM-GBSA postdocking scoring protocol, to correctly rank a number of congeneric kinase inhibitors was assessed and suggests that this may be useful for the design of inhibitors in the lead optimization phase of drug discovery.

TL;DR: It demonstrated rapid induction of apoptosis and subsequent cell death broadly across hematologic cancer models in vitro, and MCL-1 depletion in a dose- and time-dependent manner was identified as a major mechanism through which AZD4573 induces cell death in tumor cells.

TL;DR: The molecular mechanism of a TAK1 irreversible inhibitor is elucidated and laid the foundation for designing next generation TAK2 irreversible inhibitors, and the NRAS-TAK1-Wnt signaling network discerned in this study may prove to be useful in patient selection for Tak1 targeted agents in hematological cancers.

TL;DR: A series of dimeric compounds based on the AVPI motif of Smac were designed and prepared as antagonists of the inhibitor of apoptosis proteins (IAPs), leading to the identification of compound 14 (AZD5582), which binds potently to the BIR3 domains of cI AP1, cIAP2, and XIAP.