Another New Senolytic Prodrug is Demonstrated to Reverse Frailty and Cognitive Function in Old Mice

Today's open access paper reports on the use of a prodrug senolytic strategy to reverse aspects of aging in mice via the selective destruction of senescent cells. A prodrug is a small molecule, usually innocuous, that can be converted into an active drug molecule by the action of specific proteins in the body. For example a drug can be made into a prodrug by the addition of further chemical structure that (a) renders it inert, and (b) is cleaved away by an enzyme inside cells. Ideally, the inactive prodrug is designed such that this conversion to an active drug molecule only takes place where and when the drug is needed. Senescent cell accumulation with age is an important cause of age-related degeneration and disease. Senescent cells are characterized by high levels of β-Galactosidase, known as senescence-associated β-Galactosidase (SA-β-Gal). Since β-Galactosidase is an enzyme that cleaves glycosidic bonds, it is possible to turn many types of drug into prodrugs that only activate to meaningful levels inside senescent cells by attaching structures that will be removed by β-Galactosidase. Researchers have recently demonstrated that this can be done with the chemotherapeutic drug navitoclax. Navitoclax is the worst of the effective first generation senolytics: it certainly kills senescent cells, and is somewhat specific, but it also kills far too many other cells for comfort. It has significant and unpleasant side-effects, but when it is made into a prodrug, thes...
Source: Fight Aging! - Category: Research Authors: Tags: Medicine, Biotech, Research Source Type: blogs