Development of an HT Screen to Identify Novel Modulators of the CRFBP
A connection between the corticotropin signaling pathway and alcohol use disorder (AUD) has been shown previously. We developed a high throughput screen to identify small molecule modulators of this pathway as potential therapeutics for AUD.
Currently available treatments for alcohol use disorder (AUD) include three pharmacotherapies approved by the Food and Drug Administration: disulfiram, naltrexone, and acamprosate. The clinical efficacy of these pharmacotherapies is marginal, and they all suffer from limiting contraindications. Thus, there is a critical need for more effective pharmacotherapies for AUD.
Innovation and Meaningful Advantages:
Growing attention has been paid to the stress system—specifically, the signaling pathway of corticotropin-releasing factor (CRF)—as a pharmacological target for AUD, and the expression pattern of CRF binding protein (CRFBP) suggests a critical role in the modulation of the stress responses. Using a novel high throughput screen we developed, we were able to identify two negative allosteric modulators (NAMs) of CRFBP.
Commercial Development: Current State and Next Steps:
We transferred this novel biological assay to our collaborator’s robotic facility and have screened >350,000 compounds. We have selected 2 allosteric modulators and tested them in an ex vivo preclinical alcohol model.
Our goal is to collaborate with biopharma partners/funders who can bring into play the developmental, translational, and financial resources needed to advance this technology into the commercial marketplace.
Carolina Haass-Koffler PhD
Associate Professor of Psychiatry and Human Behavior
Brown Tech ID #2579
2021-10-07; US 2021/0308107A1; published.
Curley DE, et al., Corticotropin-releasing factor-binding protein as a novel target to restore brain homeostasis: lessons learned from alcohol use disorder research. Frontiers in Behavioral Neuroscience, section Motivation, and Reward (in press)
Haass-Koffler CL, et al., Defining the Role of Corticotropin-Releasing Factor Binding Protein in alcohol consumption, Translational Psychiatry 2016 PMID: 27845775, PMCID: PMC3434418
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