Don't stress about CRF: assessing the translational failures of CRF₁antagonists.

ABSTRACT:

Background

Dr. Athina Markou sought treatments for a common neural substrate shared by depression and drug dependence. Antagonists of corticotropin-releasing factor (CRF) receptors, a target of interest to her, have not reached the clinic despite strong preclinical rationale and sustained translational efforts.

Methods

We explore potential causes for the failure of CRF₁ antagonists and review recent findings concerning CRF-CRF₁ systems in psychopathology.

Results

Potential causes for negative outcomes include (1) poor safety and efficacy of initial drug candidates due to bad pharmacokinetic and physicochemical properties, (2) specificity problems with preclinical screens, (3) the acute nature of screens vs. late-presenting patients, (4) positive

SUBMITTER: Spierling SR 

PROVIDER: S-EPMC5420464 | biostudies-literature | 2017 May

REPOSITORIES: biostudies-literature