JTE-151 / Japan Tobacco, Orphagen - LARVOL DELTA

Discovery and SAR of JTE-151: A novel RORγ inhibitor for clinical development (ACS-Fall 2025) - "Although the exact reasons for hampering their advancement are not clearly understood, there are some plausible causes to be evoked when the nature of the target protein is taken into consideration. In this presentation, we disclose SAR exploration toward JTE-151 which is our first clinical compound of RORg inhibitor, including the pharmacological effects in animal models and the human PK profiles in the Phase I clinical trial."

Clinical • Inflammation • CD4 • IL17A • IL6

Suppressive Effects of JTE-151, a Novel Orally Available RORγ Antagonist, in Experimental Models of Rheumatoid Arthritis. (PubMed, Biol Pharm Bull) - "Furthermore, co-administration of JTE-151 and anti-tumor necrosis factor α (TNFα) antibody, compared with each administered individually, resulted in a stronger effect on the arthritis symptoms in CIA mice. These results suggest that JTE-151 has the potential to become a new treatment option for patients with RA."

Journal • Immunology • Inflammation • Inflammatory Arthritis • Oncology • Rheumatoid Arthritis • Rheumatology • TNFA

Pharmacological Inhibition of RORγ Ameliorates Skin Inflammation Induced by Both Antigen- and Cytokine-Activated Th17 Cells. (PubMed, Biol Pharm Bull) - "Taken together, we showed that pharmacological inhibition of RORγ by JTE-151 suppressed the activation of Th17 cells induced by both antigen and cytokine, and that it also ameliorated skin inflammation following Th17 cell activation. These results suggest that RORγ antagonists, including JTE-151, have the potential to become drug candidates for fighting psoriasis and other Th17-related autoimmune diseases, and that pharmacological inhibition of RORγ may also have broader effects than Th17-related cytokine-specific biological agents."

Journal • Dermatitis • Dermatology • Immunology • Inflammation • Psoriasis • Solid Tumor • IL12A • IL17A • IL22 • IL23A

A Concise and Modular Approach to Generate Novel RORγ Agonists. (PubMed, J Med Chem) - "A variety of RORγ inhibitors have been identified, including clinical compounds such as VTP-43742 and JTE-151. In contrast, RORγ agonists have been less explored and LYC-55716 is, to the best of our knowledge, the sole example reached a human clinical investigation...This scaffold was subjected to final optimization by attaching function-oriented modules retaining druglike properties. After multiparameter optimization, novel selective RORγ agonists were discovered, and their in vivo effects were confirmed in a syngeneic mouse model after oral administration."

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Pharmacological Properties of JTE-151; A Novel Orally Available RORγ Antagonist That Suppresses Th17 Cell-Related Responses in Vitro and in Vivo. (PubMed, Biol Pharm Bull) - "Furthermore, treatment with JTE-151 suppressed the production of IL-17 in antigen-sensitized mice and ameliorated the severity of arthritis in mice with collagen-induced arthritis regardless of treatment start date. Based on these results, we reasoned that JTE-151 could serve as a novel therapeutic compound for various autoimmune diseases linked to Th17 cells, such as psoriasis and rheumatoid arthritis."

Journal • Preclinical • Dermatology • Immunology • Inflammatory Arthritis • Psoriasis • Rheumatoid Arthritis • Rheumatology • CD4 • IFNG • IL17A • IL4

Discovery and SAR of JTE-151: A Novel RORγ Inhibitor for Clinical Development. (PubMed, J Med Chem) - "After an intensive SAR exploration with strong emphasis on "drug-likeness" indices, an orally available RORγ inhibitor, JTE-151, was finally generated and was advanced to a human clinical trial. The compound was confirmed to possess highly selective profiles along with good metabolic stability, and most beneficially, no serious adverse events (SAE) and good PK profiles were observed in the human clinical trial."

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