Our approach will result in novel pharmacological treatments that are selective for senescent cells and designed to improve tolerability in older, frail, and sick individuals.
The small molecules developed from our our discovery platform ALEMBIC are engineered to be selectively activated in target cells that emerge with age-related diseases driving the chronic degenerative pathology. We recently released in pre-print, currently under peer-review, a proof of concept paper where we present initial results on a tool compound that is based on a prodrug strategy. This approach takes advantage of a known enzymatic activity enriched in senescent cells, the hydrolase beta-Galactosidase, well known to be a marker of senescent cells. Our data demonstrates this strategy of converting a pan-cytotoxic drug into a selective and well tolerated senolytic prodrug capable of ameliorating age-related diseases such as Frailty and the loss of cognitive and muscle function, in geriatric preclinical models (Doan et al., 2020).
At Rubedo we are advancing novel generations of small molecule leads that are more sophisticated and potent. These compounds are based on different metabolic functions, beyond Beta-galactosidase, that we discovered and applied in the design of our engineered small molecules aimed toward clinical development to treat specific unmet clinical needs.