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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Bioactivity Comments |
The DC50 values of LL-K9-3 for CDK9 and cyclin T1 are 0.66 and 0.59 μM respectively [1]. The ligand entry for BMS-387032 (a.k.a. SNS032) provides affinity/potency data for the CDK9-directed component of LL-K9-3 across a number of CDKs. |