molecules of the month


folate receptor-dependent PROTAC conjugate

FOLR1-dependent MEK1/2 degrad. in vitro

rom conjugation of folate to PROTAC

J. Am. Chem. Soc., May 10, 2021

Harvard Medical / Mt. Sinai

1 min read

The FOLR1-targeting folate receptor-dependent PROTAC conjugate, folate-MS432, is a MEK1/2 degrader that is targeted to FOLR1, a receptor highly expressed in many cancer cell types but less so in most normal cells. The folate moiety allows the molecule to be taken up into cells via endocytosis, where the inert molecule can be cleaved by intracellular hydrolases to release the active MEK1/2 degrader. In theory, this strategy could increase the therapeutic windows of degraders against targets with known safety issues upon inhibition, such as MEK1/2. While folate-targeting as a strategy has been attempted in the past (such as in our recent highlight of PDB-folate conjugate EC2629), there has not been much clinical success yet. Like ADCs, there are additional issues to consider, such…

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