AU-18069

Lead candidate AU-18069 demonstrated that selective CBP/p300 bromodomain inhibitors are efficacious in models of hematologic malignancies and solid cancers in vitro and in vivo. Further evaluation of efficacy in other xenograft models, as a single agent as well as in combination with other agents is planned. Long term toxicological and safety pharmacology evaluation in different species and other IND enabling studies are in progress to support progression of this compound to clinical trials.

Multiple potent and selective CBP/p300 BRD inhibitors that are structurally unrelated to known inhibitors have been identified by iterative medicinal chemistry and SAR based approaches. The lead compound, AU-18069 was optimized towards attaining good potency, physicochemical properties and DMPK profile. AU-18069 potently inhibited viability and proliferation of a wide range of cell lines derived from prostate cancer, CBP mutant and MYC-dependent hematological cancers and demonstrated improved PK profile in rodent models in comparison with a compound, currently in clinical trials.

In summary, our studies demonstrate that selective CBP/p300 bromodomain inhibitors are potent in models of hematologic malignancies and solid tumors in-vitro. Profiling of efficacy in xenograft models, and further toxicological evaluation are in progress.