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molecules of the month

SY-5609

oral picomolar & reversible CDK7 inhibitor

Ph. I candidate in breast cancer comb. Therapy

from previous CDK7 inhibitor SY-1365

Journal of Medicinal Chemistry

Syros Pharmaceuticals Inc.

Chemical structure of molecule SY-5609 Syros Pharmaceuticals CDK7 kinase inhibitor
1 min read

4. The Syros Pharmaceuticals CDK7 kinase inhibitor, SY-5609, is a picomolar, reversible, and highly selective molecule with slow off-rate kinetics.  It follows a prior covalent clinical candidate from Syros. The molecule is >4000x selective vs. the nearest known off-target among 485 kinases profiled. Cyclin-dependent kinase inhibitors have seen a resurgence in interest recently as previous issues with family selectivity and potential toxicity now seem surmountable. This is thanks to a combination of biomarker-focused clinical development and the success of combination regimens and patient selection for CDK4/6 inhibitors as well as wealth of industry kinase drug discovery experience. This inhibitor is a rare example of a phosphine-oxide containing clinical candidate, though the motif is likely to be more frequently used due to…


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