A CNS-Targeting Prodrug Strategy for Nuclear Receptor Modulators

20 May 2020, Version 1
This content is a preprint and has not undergone peer review at the time of posting.


Neurodegenerative diseases lack a breadth of treatment options due, in part, to the known difficulties associated with a drug’s passage across the blood-brain barrier. In this study, we provide a blueprint for how to get drug-like structures which feature carboxylic acid motifs across the blood-brain barrier, while attenuating their peripheral exposure using a chemical prodrug strategy. This prodrug strategy utilizes endogenous fatty-acid amide hydrolase expressed in the CNS to cleave and release parent drugs for CNS drug action to commence. In particular, we demonstrate the successes and limitations of this prodrug strategy within a series of nuclear receptor modulators, which have shown promise as potential therapeutics for neurodegenerative diseases.


Nuclear Receptors


Comments are not moderated before they are posted, but they can be removed by the site moderators if they are found to be in contravention of our Commenting Policy [opens in a new tab] - please read this policy before you post. Comments should be used for scholarly discussion of the content in question. You can find more information about how to use the commenting feature here [opens in a new tab] .
This site is protected by reCAPTCHA and the Google Privacy Policy [opens in a new tab] and Terms of Service [opens in a new tab] apply.