Key points from article :
New approach demonstrated to improve Navitoclax characteristics as a senolytic drug.
It is validated in preclinical models showing high potency to kill senescent cells (SC).
A feature of SC is their enrichment of senescence-associated β-galactosidase (SA-β-gal).
They modified Navitoclax with an acetylated galactose.
This is to exploit enriched SA-β-gal activity of the SC.
Model systems show results of galacto-conjugation of Navitoclax (Nav-Gal).
It results in a prodrug with selective, pro-apoptotic senolytic activity.
Which is released in SC that is dependent on GLB1 activity.
It reduces thrombocytopenia in treated mice at therapeutically effective doses.
As well as apoptosis of platelets in human blood samples treated ex vivo.
Galacto-conjugation of cytotoxic drugs as a versatile methodology proposed.
For developing second-generation prodrugs with high senolytic activity, reduced toxicity.
Published in Aging Cell.
