Mark Zak

TL;DR: It is shown that, owing to distinct mechanisms regulating MEK activation in KRAS- versus BRAF-driven tumours, different mechanisms of inhibition are required for optimal antitumour activity in each genotype.

TL;DR: It is shown that retrosynthetic analysis of thiostrepton reveals compounds 23, 24, 26, 28, and 29 as potential key building blocks for the projected total synthesis, and a method was developed for the direct coupling of the labile dehydropiperidine key building block 28 to the more advanced and stable peptide intermediate 27 through capture with the highly reactive alanine equivalent 67.

TL;DR: This concept was illustrated by a set of optimized procedures for the Suzuki cross-coupling and the borono-Mannich reactions, which helps eliminate time-consuming cleavage and transfer operations, thereby considerably simplifying the outlook of combinatorial library synthesis by manual or automated means.

TL;DR: The results indicate that the biological processes that require TYK2 catalytic function in humans are restricted to the IL-12 and IL-23 pathways, and suggest that inhibition of tyrosine kinase catalytic activity may be an efficacious approach for the treatment of select autoimmune diseases without broad immunosuppression.