Basimglurant
Chemical compound
From Wikipedia, the free encyclopedia
Basimglurant (INN; developmental code RG-7090 and RO-4917523) is a negative allosteric modulator of the mGlu5 receptor which is under development by Roche and Chugai Pharmaceutical for the treatment of treatment-resistant depression (as an adjunct) and fragile X syndrome.[1][2] As of November 2016, it has undergone phase II clinical trials for both of these indications.[3]
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| Routes of administration | By mouth |
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| Formula | C18H13ClFN3 |
| Molar mass | 325.77 g·mol−1 |
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It was discovered in a medicinal chemistry effort conducted at Roche starting from the results of a small molecular weight compound library high-throughput screen based on a Ca21 mobilization assay with human mGlu5a (Jaeschke et al., 2015). The high-throughput screen identified several mGlu5 antagonists such as MPEP, MTEP, and fenobam.[4] In partnership with Chugai Pharmaceutical, basimglurant is currently still undergoing revision from previous drug trials as of November 2016.[3]
Pharmacology
Mechanism of action
Preclinical research trials found that basimglurant has a high specificity for the glutamate receptor mGlu5, and as a consequence of this specificity, also has a high level of safety.[4]
Pharmacokinetics
Preclinical drug trials showed that basimglurant possessed a terminal half-life of 7 hours in rats and 20 hours in monkeys, indicating a dosing regimen of once daily in possible human patients.[4] Research with rats and monkeys revealed a bioavailability of 50%, with additional studies showing that basimglurant has a rate of plasma protein binding of 98 to 99%.[4]
Clinical trials
Phase I clinical trials for basimglurant began in April 2015, and finished in September 2015. 56 people were spread out among 4 healthy cohorts, a major depressive disorder cohort, and a placebo cohort. The trial was undertaken to study (and verify) the safety of basimglurant as a potential drug. Completion of this trial allowed for basimglurant to begin phase II drug trials.[5]
Phase II clinical trials have been undertaken, and a lack of efficacy was found overall. Improved secondary endpoints though of 1.5 mg dosage has prompted future clinical trials of the drug.[1][2][6]
Future
Basimglurant has shown the desired characteristics of a drug with high bioavailability, few safety liabilities, and promise in the secondary endpoints of a phase IIb trial, it will most likely undergo future iterations and attempt to pass drug trials again.
History
Basimglurant was originally developed for the treatment of fragile X syndrome,[7] but after failing phase II clinical trials Roche abandoned the drug in this field of application and is renewing basimglurant as part of a treatment for depression.