937366-57-9Relevant articles and documents
Discovery of SY-5609: A Selective, Noncovalent Inhibitor of CDK7
Marineau, Jason J.,Hamman, Kristin B.,Hu, Shanhu,Alnemy, Sydney,Mihalich, Janessa,Kabro, Anzhelika,Whitmore, Kenneth Matthew,Winter, Dana K.,Roy, Stephanie,Ciblat, Stephane,Ke, Nan,Savinainen, Anneli,Wilsily, Ashraf,Malojcic, Goran,Zahler, Robert,Schmidt, Darby,Bradley, Michael J.,Waters, Nigel J.,Chuaqui, Claudio
, p. 1458 - 1480 (2021/11/18)
CDK7 has emerged as an exciting target in oncology due to its roles in two important processes that are misregulated in cancer cells: cell cycle and transcription. This report describes the discovery of SY-5609, a highly potent (sub-nM CDK7 Kd) and selective, orally available inhibitor of CDK7 that entered the clinic in 2020 (ClinicalTrials.gov Identifier: NCT04247126). Structure-based design was leveraged to obtain high selectivity (>4000-times the closest off target) and slow off-rate binding kinetics desirable for potent cellular activity. Finally, incorporation of a phosphine oxide as an atypical hydrogen bond acceptor helped provide the required potency and metabolic stability. The development candidate SY-5609 displays potent inhibition of CDK7 in cells and demonstrates strong efficacy in mouse xenograft models when dosed as low as 2 mg/kg.
CDK inhibitor based on organic arsine as well as preparation method and application of CDK inhibitor
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Paragraph 0148-0150; 0160-0162, (2021/03/31)
The invention provides a CDK inhibitor based on organic arsine as well as a preparation method and application of the CDK inhibitor. Specifically, the invention providese compounds of Formula I, or stereoisomers or tautomers thereof, or pharmaceutically acceptable salts, hydrates or solvates thereof; and the invention also discloses a preparation method and application thereof. Definitions of allgroups in the formula are shown in the specification.
Pyrimidine amine compound, and preparation method and application thereof
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Paragraph 0236-0237; 0243-0244, (2020/07/02)
The invention discloses a polycyclic compound, and a preparation method and an application thereof. The invention provides the polycyclic compound represented by formula I, or a pharmaceutically acceptable salt thereof. The compound has a relatively good inhibition effect on CDK7.