The astressins are unique peptide candidates exclusively licensed from the Salk Institute that block the effects of CRF. Indeed, the astressins block both CRF1 and CRF2 receptors that Sentia believes are important for treating certain stress-related conditions. These peptide antagonists offer several attributes:
- Firstly, peptides may offer safety advantages. In this regard, no adverse effects resulting from the administration of astressin B to mice, rats, monkeys or early-weaned piglets under basal (non-stressed) conditions have been observed. These unique properties afford the opportunity to treat stress-related conditions in a safe and effective manner.
- Secondly, the unique properties of astressins result in long-acting effects, thus providing a solution for prolonged maintenance of homeostasis.
- Lastly, the astressins interact with the CRF1/2 receptors to block directly the initial event of CRF receptor binding, while non-peptide CRF antagonists bind exclusively at internal sites removed from the ligand-receptor domain. Sentia believes that blocking the hormone binding sites on the outside extracellular domain of the receptor may enhance the probability of obtaining receptor selectivity for some astressins.
The figure shows the long-acting activity of astressin C to reduce elevated ACTH levels in adrenalectomized rats1. (*Normally the adrenal glands produce cortisol that acts as a brake on ACTH production from the pituitary gland. Adrenalectomy is a procedure that removes the adrenal glands and eliminates this negative feedback resulting in elevated ACTH levels). The black line shows chronically elevated levels of ACTH that mimics the effects of chronic stress. A single administration of all doses of astressin C resulted in dose-dependent suppression of ACTH for more than a week and a sustained long-lasting return of the system closer to basal levels as shown by the green line depicting the 1.0 mg/rat dose. The points represent the mean ± standard deviation.
1 Erchegyi et. al., (2016) J. Med. Chem., 59, 854-866