Ensemble Therapeutics Corp.

Affinity selection screening of macrocycle libraries derived from DNA-programmed chemistry identified XIAP BIR2 and BIR3 domain inhibitors that displace bound pro-apoptotic caspases. X-ray cocrystal structures of key compounds with XIAP BIR2 suggested potency-enhancing structural modifications. Optimization of dimeric macrocycles with similar affinity for both domains were potent pro-apoptotic agents in cancer cell lines and efficacious in shrinking tumors in a mouse xenograft model.

A hemicyanine fluorescent dye I was attempted to be generated by DNA-templated, aldol-type condensation from nonfluorescent precursors in the presence of 11 different diamines.Studies of reaction rate and yield as a function of catalyst structure indicated the diamine catalyst operates in a concerted mechanism on both reaction components.