Discovery of JAB-3312, a Potent SHP2 Allosteric Inhibitor for Cancer Treatment.

As an oncogenic phosphatase, SHP2 acts as a converging node in the RTK-RAS-MAPK signaling pathway in cancer cells and suppresses antitumor immunity by passing signals downstream of PD-1. Here, we utilized the extra druggable pocket outside the previously identified SHP2 allosteric tunnel site by the (6,5 fused), 6 spirocyclic system. The optimized compound, , exhibited a SHP2 binding of 0.

Photoinduced chlorine atom-transfer cyclization/photohydrolysis of 3-acyl-2-chloro-N-(ω-phenylalkynyl)pyrroles: a one-pot synthesis of benzoyl-substituted fused pyrroles.

A one-pot synthesis of benzoyl-substituted fused pyrroles or indoles in moderate to high yields has been achieved by the photocyclization/photohydrolysis reactions of N-(ω-phenylalkynyl)-2-chloropyrrole-3-carbaldehydes or 3-acyl-N-(ω-phenylbutynyl)-2-haloindoles in wet acetone. The formation of all these products could be inferred by a two-step reactions, namely, photoinduced chlorine atom-transfer cyclization and subsequent photohydrolysis.