THAL-SNS-032

THAL-SNS-032 is a selective CDK9 degrader consisting of a CDK-binding SNS-032 ligand linked to a thalidomide derivative which binds the E3 ubiquitin ligase Cereblon (CRBN). THAL-SNS-032 induces rapid degradation of CDK9 without affecting the levels of other SNS-032 targets. The transcriptional changes elicited by THAL-SNS-032 are more like those caused by NVP-2 than those induced by SNS-032. Strikingly, compound washout does not significantly reduce levels of THAL-SNS-032-induced apoptosis, suggesting that CDK9 degradation had prolonged cytotoxic effects compared to CDK9 inhibition.^[1]

• Cell lines

  Wildtype MOLT4 cells, CRBN−/− MOLT4 cells

• Concentrations

  250nM

• Incubation Time

  6 h, 72 h

• Method

  Proliferation assays are performed by treating MOLT4 and CRBN−/− MOLT4 cells with THAL-SNS-032 at concentrations indicated for 72 hours. Anti-proliferative effects of compounds are assessed using Cell Titer Glo assay kit. IC50s are determined using Graphpad Prism non-linear regression curve fit. To determine the effect of washout, MOLT4 and CRBN−/− MOLT4 cells are treated with 250nM THAL-SNS-032. After 6 hours, compound is washed from cells by washing cells with media three times where indicated. Cells are allowed to grow for another 66 hours (72-hour total) and assayed for anti-proliferation using Cell Titer Glo assay kit.