I-BET151

I-BET151 is an isoxazole class pan-BET family inhibitor, blocking BRD2, BRD3, and BRD4 with IC₅₀ values of 0.5, 0.25, and 0.79 µM, respectively.^1,2,3,4 Through this action, it blocks the growth of leukemic cell lines driven by mixed lineage leukemia (MLL) fusions at nanomolar concentrations, whereas tyrosine kinase activated cells were much less sensitive.⁵ Specifically, I-BET151 induces apoptosis via reduced expression of BCL2 or triggers G₀/G₁ cell cycle arrest in MLL-fusion cell lines.⁵ I-BET151 is effective in vivo, suppressing MLL leukemia progression in two different mouse models.⁵ This product is also available as part of Cayman's Astrocyte Reprogramming Reagent Kit (DFICBY) (Item No. 502887).

WARNING This product is not for human or veterinary use.

1. Kline, T.B., Benington, F., Morin, R.D., et al. Structure-activity relationships for hallucinogenic N,N-dialkyltryptamines: Photoelectron spectra and serotonin receptor affinities of methylthio and methylenedioxy derivatives. J. Med. Chem. 25(11), 1381-1383 (1982).

2. Vidler, L.R., Brown, N., Knapp, S., et al. Druggability analysis and structural classification of bromodomain acetyl-lysine binding sites. J. Med. Chem. 55(17), 7346-7359 (2012).

3. Hewings, D.S., Fedorov, O., Filippakopoulos, P., et al. Optimization of 3,5-dimethylisoxazole derivatives as potent bromodomain ligands. J. Med. Chem. 56(8), 3217-3227 (2013).

4. Dawson, M.A., Kouzarides, T., and Huntly, B.J. Targeting epigenetic readers in cancer. N. Engl. J. Med. 367(7), 647-657 (2012).

5. Dawson, M.A., Prinjha, R.K., Dittmann, A., et al. Inhibition of BET recruitment to chromatin as an effective treatment for MLL-fusion leukaemia. Nature 478(7370), 529-533 (2011).