Small molecule targets incurable leukaemia
Heidelberg/Cambridge/London– A team of researchers from GlaxoSmithKline, the biotech company Cellzome and from Universities Cambridge, Ulm and Amsterdam have found a promising treatment for mixed lineage (MLL-fusion) leukaemia (Nature, doi; 10.1038/nature10509). Their small molecule inhibitor I-BET151 blocks a transcriptiomal regulator called bromodomain and extra terminal (BET) protein, which can be selectively targeted to displace the proteins from chromatin. For the first time, Tony Kouzarides and colleagues demonstrated that BET proteins are associated with MLL fusion proteins, which are involved in leukaemia pathogenesis. In mice, I-BET151 provided excellent control of MLL leukaemia progression, inducing cell cycle arrest and programmed cell death as well as inhibition of transcription of key genes. The partners see huge potential of BET inhibitors for clinical studies. Dr.
David Simmons, CSO of Cellzome commented “The publication shows how our chemoproteomic technology can guide epigenetic drug discovery. This new and exciting field of biology offers great potential for developing novel therapeutic interventions as personalised epigenetic medicines”