4.3 Article

Absorption, metabolism, and excretion of [14C]dersimelagon, an investigational oral selective melanocortin 1 receptor agonist, in preclinical species and healthy volunteers

Journal

PHARMACOLOGY RESEARCH & PERSPECTIVES
Volume 11, Issue 3, Pages -

Publisher

JOHN WILEY & SONS LTD
DOI: 10.1002/prp2.1084

Keywords

absorption; dersimelagon; erythropoietic protoporphyria; excretion; metabolism; X-linked protoporphyria

Ask authors/readers for more resources

Dersimelagon is a novel agonist for melanocortin 1 receptor being investigated for the treatment of erythropoietic protoporphyria, X-linked protoporphyria, and diffuse cutaneous systemic sclerosis (dcSSc). Studies in both humans and animals have shown that Dersimelagon is rapidly absorbed and eliminated, with a primary route of excretion being through feces. It is extensively metabolized in the liver and excreted in bile. These findings support the continued development of Dersimelagon for the treatment of photosensitive porphyrias and dcSSc.
Dersimelagon (formerly MT-7117) is a novel, orally administered nonpeptide small molecule selective agonist for melanocortin 1 receptor currently being investigated for the treatment of erythropoietic protoporphyria, X-linked protoporphyria, and diffuse cutaneous systemic sclerosis (dcSSc). Findings of studies evaluating the absorption, distribution, metabolism, and excretion (ADME) of dersimelagon following a single dose of [C-14]dersimelagon in healthy adult volunteers (N = 6) who participated in phase 1, single-center, open-label, mass balance study (NCT03503266), and in preclinical animal models are presented. Rapid absorption and elimination were observed following oral administration of [C-14]dersimelagon in clinical and nonclinical studies, with a mean T-max of 30 min in rats and 1.5 h in monkeys, and a median T-max of 2 h in humans. In rats, there was a widespread distribution of [C-14]dersimelagon-related material, but little or no radioactivity was detected in the brain or fetal tissues. In humans, elimination of radioactivity in urine was negligible (excretion of radioactivity into the urine: 0.31% of dose), and the primary route of excretion was feces, with more than 90% of the radioactivity recovered through 5 days postdose. Based on these findings, dersimelagon is not retained in the human body. Findings from humans and animals suggest dersimelagon is extensively metabolized to the glucuronide in the liver, which is eliminated in bile, and hydrolyzed to unchanged dersimelagon in the gut. The results to date for this orally administered agent elucidate the ADME of dersimelagon in human and animal species and support its continued development for the treatment of photosensitive porphyrias and dcSSc.

Authors

I am an author on this paper
Click your name to claim this paper and add it to your profile.

Reviews

Primary Rating

4.3
Not enough ratings

Secondary Ratings

Novelty
-
Significance
-
Scientific rigor
-
Rate this paper

Recommended

No Data Available
No Data Available