Compound class:
Synthetic organic
Comment: LL-K9-3 is a small-molecule that induces simultaneous degradation of CDK9 and cyclin T1 (CDK9-Cyclin T1 heterodimers) that was developed for anti-tumour potential in transcriptionally addicted cancers [1]. It uses hydrophobic tagging technology (HyT) to induce polyubiquitination of CDK9-cyclin T1 complexes, as a mechanism to promote proteasome-mediated degradation of both proteins. In particular LL-K9-3 was evaluated for its inhibitory effects on CDK9 and androgen receptor-mediated signalling pathways in prostate cancer. LL-K9-3 elicits more potent anti-proliferative and pro-apoptotic effects than its parental CDK9 inhibitor BMS-387032 (a.k.a. SNS032), or than the CDK9-only PROTAC THAL-SNS-032.
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References |
1. Li J, Liu T, Song Y, Wang M, Liu L, Zhu H, Li Q, Lin J, Jiang H, Chen K et al.. (2022)
Discovery of Small-Molecule Degraders of the CDK9-Cyclin T1 Complex for Targeting Transcriptional Addiction in Prostate Cancer. J Med Chem, 65 (16): 11034-11057. [PMID:35925880] |