1. Discovery and first-time disclosure of CVN766, an exquisitely selective orexin 1 receptor antagonist.
- Author
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Glen A, Bürli RW, Livermore D, Buffham W, Merison S, Rowland AE, Newman R, Fieldhouse C, Miller DJ, Dawson LA, Matthews K, Carlton MB, and Brice NL
- Subjects
- Humans, Orexins, Orexin Receptor Antagonists pharmacology, Orexin Receptors, Disclosure, Mental Disorders
- Abstract
Modulators of orexin receptors are being developed for neurological illnesses such as sleep disorders, addictive behaviours and other psychiatric diseases. We herein describe the discovery of CVN766, a potent orexin 1 receptor antagonist that has greater than 1000-fold selectivity for the orexin 1 receptor over the orexin 2 receptor and demonstrates low off target hits in a diversity screen. In agreement with its in vitro ADME data, CVN766 demonstrated moderate in vivo clearance in rodents and displayed good brain permeability and target occupancy. This drug candidate is currently being investigated in clinical trials for schizophrenia and related psychiatric conditions., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: All authors were either full time employees of Takeda Cambridge or Cerevance Ltd., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)
- Published
- 2024
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