Discovery of MT-7117 (Dersimelagon Phosphoric Acid): A Novel, Potent, Selective, and Nonpeptidic Orally Available Melanocortin 1 Receptor Agonist.

Activation of the melanocortin 1 receptor (MC1R) mediates melanogenesis in melanocytes, anti-inflammatory effects in inflammatory cells, and antifibrotic effects in fibroblasts. Thus, MC1R agonists are expected to be beneficial for treating skin, autoimmune, inflammatory, and fibrotic diseases. Afamelanotide, an α-melanocyte-stimulating hormone (α-MSH) analogue MC1R agonist, is used clinically for treating erythropoietic protoporphyria (EPP) as a subcutaneous implant formulation.

Treatment Patterns of Biologic Disease-Modifying Antirheumatic Drugs and Janus Kinase Inhibitors in Patients with Rheumatoid Arthritis in Japan: A Claims-Based Cohort Study.

Background: Reports on treatment patterns of biologic disease-modifying antirheumatic drugs (bDMARDs)/Janus kinase inhibitors (JAKi) for rheumatoid arthritis (RA) in clinical practice are still sparse in Japan, especially in combination with conventional synthetic DMARDs (csDMARDs).

Objectives: The aim of this study was to investigate treatment patterns of bDMARD/JAKi in the treatment of RA in real-world clinical practice in Japan.

Method: A retrospective cohort study was conducted using the Japanese Medical Data Vision health claims database.

A Real-World Claims Database Study Assessing Long-Term Persistence with Golimumab Treatment in Patients with Rheumatoid Arthritis in Japan.

Introduction: The persistence of golimumab (GLM) treatment in Japanese patients with rheumatoid arthritis (RA) has been evaluated previously, but evidence of long-term real-world use is lacking. This study assessed the long-term persistence of GLM use, its influencing factors, and impact of prior medications in patients with RA in actual clinical practice in Japan.

Methods: This is a retrospective cohort study of patients with RA using data from a hospital insurance claims database in Japan.

Discovery of novel N-(1-benzyl-1H-imidazol-2-yl)amide derivatives as melanocortin 1 receptor agonists.

Melanocortin-1 receptor (MC1R) is primarily activated by α-melanocyte-stimulating hormone (α-MSH) and plays a crucial role, such as keeping homeostasis in the skin against melanogenesis and external stimuli, anti-inflammatory effects, and tissue fibrosis suppression. Afamelanotide, an α-MSH analog MC1R agonist, is clinically used for treating erythroblastic protoporphyria (EPP) by subcutaneous implantation administration. Therefore, we initiated an investigation aimed at orally available small molecule nonpeptide MC1R agonists.

Dersimelagon, a novel oral melanocortin 1 receptor agonist, demonstrates disease-modifying effects in preclinical models of systemic sclerosis.

Background: Activation of melanocortin 1 receptor (MC1R) is known to exert broad anti-inflammatory and anti-fibrotic effects. The purpose of this study is to investigate the potential of dersimelagon, a novel oral MC1R agonist, as a therapeutic agent for systemic sclerosis (SSc).

Methods: The effects of dersimelagon phosphoric acid (MT-7117) on skin fibrosis and lung inflammation were evaluated in bleomycin (BLM)-induced SSc murine models that were optimized for prophylactic and therapeutic evaluation.