Targeting the menin-MLL interaction with small molecules represents an attractive strategy to develop new anticancer agents. Using our proprietary SCULPT technology and X-Ray crystal structures, novel molecules with drug-like properties are designed, synthesized and are being evaluated in vitro and in vivo. These molecules show more selectivity and potency than current treatments. This work is being carried out in collaboration with Biomea Healthcare in a 50/50 partnership to advance this Leukemia program to IND in 2019.
The transcription factor yes-associated protein-1 (YAP) plays a central role in hippo signalling pathway, facilitating a range of pro-growth and anti-apoptotic processes. Overexpression of YAP has been characterized in patients encompassing a wide range of different cancers. Critical to YAP mediated oncogenicity is engagement with the transcription factor TEAD.
While there is extensive characterization of the essentially of the YAP-TEAD interaction in several different malignancies, there has been substantial difficulty in the development of potent inhibitors. This can be attributed to the unique topological features of the TEAD protein, particularly at the interface of the interaction with YAP. The SCULPT platform enables the chemical tractablilty of this unique architecture through several dozen iterations of molecular design.