Brian Dymock

TL;DR: The data show that NVP-AUY922 is a potent, novel inhibitor of HSP90, acting via several processes (cytostasis, apoptosis, invasion, and angiogenesis) to inhibit tumor growth and metastasis.

TL;DR: The structure-based design, synthesis, structure-activity relationships and pharmacokinetics of potent small-molecule inhibitors of Hsp90 based on the 4,5-diarylisoxazole scaffold are described and analogues from this series have high affinity for HSp90, as measured in a fluorescence polarization (FP) competitive binding assay, and are active in cancer cell lines.

TL;DR: The structures of the HSP90alpha N-terminal domain complexed with the purine-based inhibitor, PU3, and analogs with enhanced potency both in enzyme and cell-based assays confirm that the molecules inhibit cell growth by a mechanism dependent on H SP90 inhibition.

TL;DR: The crystal structure of a previously reported screening hit 1 (CCT018159) bound to the N terminal domain of molecular chaperone Hsp90 has been used to design 5-amide analogues that exhibit enhanced potency against the target in binding and functional assays with accompanying appropriate cellular pharmacodynamic changes.

TL;DR: SB1518 has a unique profile and is efficacious and well tolerated in JAK2-dependent models, now being confirmed in clinical studies in patients with myelofibrosis and lymphoma.