BAY2666605

Molecular glues are compounds that induce proximity between two proteins, typically by stabilizing a low-affinity interaction. BAY 2666605 represents a new class of molecular glues called Velcrins with cell-selective cytotoxic properties. Velcrin compounds are molecular glues that kill a subset of cancer cells expressing PDE3A and SLFN12 by inducing complex formation between these two proteins. SLFN12 is an RNase, such that binding to PDE3A increases SLFN12 RNase activity, and that SLFN12 RNase activity is required for velcrin response. Discovery of the physiological substrate of SLFN12, tRNA-Leu-TAA, has facilitated elucidation of the mechanism of action of velcrin compound BAY 2666605 exhibit superior physicochemical and pharmacokinetic properties making it an ideal chemical probe for exploring the biological role of PDE3A/SLFN12 expressing cells. I would highly recommend using BAY 2666605 at IC50's less than 100 nM in cellular assays and at 5 mg/kg BID in in vivo mouse efficacy models.