mGlu3 PAM / Addex - LARVOL DELTA

Discovery of VU6052959/BI'7927: A Selective mGlu3 Positive Allosteric Modulator (PAM) from an Orthogonal Benzoxazine Chemotype. (PubMed, ACS Med Chem Lett) - "A high-throughput screening (HTS) campaign identified a selective mGlu3 PAM VU6046180/BI'3690 (7) containing a benzoxazine core (an orthogonal chemotype to previously reported thiophene tool compound VU6053371/BI'8809 (6))...Orthogonal PAM 8 demonstrated efficacy in a rat novel object recognition task with conservation of our previously determined PK/PD relationship. However, an Ames positive metabolite halted further progression of 8."

Journal

Discovery of VU6053371/BI03738809: A First-in-Class Selective and CNS-Penetrant mGlu3 Positive Allosteric Modulator (PAM) with Efficacy in a Preclinical Cognition Model. (PubMed, ACS Chem Neurosci) - "A high-throughput screening campaign identified a potent and selective mGlu3 PAM VU6048261/DI013166572 based on a tetra-substituted thiophene core but with poor DMPK properties...Thus, selective activation of mGlu3 represents a novel mechanism to address the cognitive impairment associated with schizophrenia (CIAS) and other neurodegenerative diseases. Moreover, the discovery of VU6053371/BI03738809 completes the group II mGlu receptor toolkit of in vivo PAM and NAM probes for both mGlu2 and mGlu3."

Journal • Preclinical • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Psychiatry • Schizophrenia