AMG 333 / Amgen - LARVOL DELTA

Material basis and mechanism of Ephedra sinica in interfering with wind-chill cold. (PubMed, Int Immunopharmacol) - "The intervention of AMG-333 affected the TRPM8 and p-P65/P65, but AMG-333 did not regulate TLR4. Taken together, alkaloid extract is the material basis for MH to improve rats' wind-chill cold and may protect rats from injury by regulating the TRPM8/TLR4-NFκB pathway and CHRM3, with ephedrine and pseudoephedrine possibly playing an important role."

Journal • Cough • Respiratory Diseases • CHRM3 • IL4 • IL6 • TNFA • TRPM8

Phase I, Double-Blind,Placebo, MAD Study to Evaluate the Safety, Tolerability, PK, and PD of AMG 333 in Healthy Subjects and Migraine Subjects (clinicaltrials.gov) - P1; N=48; Recruiting; Sponsor: Amgen; Not yet recruiting -> Recruiting

Enrollment open • Acute Coronary Syndrome • Biosimilar • Chronic Kidney Disease • Heart Failure • Immunology • Migraine • Renal Cell Carcinoma

Discovery of TRPM8 Antagonist (S)-6-(((3-fluoro-4-(trifluoromethoxy)phenyl)(3-fluoropyridin-2-yl)methyl)carbamoyl)nicotinic acid (AMG 333), a Clinical Candidate for the Treatment of Migraine. (PubMed, J Med Chem) - "This disclosure focuses on medicinal chemistry efforts to im-prove drug-like properties of initial leads, particularly removal of CYP3A4 induction liability and improvement of PK properties. A novel series of biarylmethanamide TRPM8 antagonists was developed, and a subset of leads were evaluated in preclinical toxicology studies to identify a clinical candidate with acceptable preclinical safety pro-file leading to clinical candidate AMG 333, a potent and highly selective antagonist of TRPM8 which was evaluated in human clinical trials."

Clinical • Journal