Progress in the development of kynurenine and quinoline-3-carboxamide derived drugs.

Progress in the development of kynurenine and quinoline-3-carboxamide derived drugs. Expert Opin Investig Drugs. 2020 Aug 21;: Authors: Boros FA, Vécsei L Abstract INTRODUCTION: The diverse neuro- and immunomodulatory effects of kynurenine pathway (KP) enzymes and metabolites exert offer possibilities for intervention in diseases such as autoimmunity, neurodegeneration and neoplastic processes. AREAS COVERED: This review focuses on data obtained from to the preclinical and clinical use of a KP metabolite analogue and structurally related compounds. 4-Cl-KYN has completed clinical trials in depression without success. However, the good safety data give hope for further trials in suicide prevention, neuropathic pain and dyskinesia. Quinoline-3-carboxiamide derivatives laquinimod, paquinimod and tasquinimod show structural similarities to kynurenines. Laquinimod and paquinimod show promising results in the treatment of autoimmune diseases, tasquinimod is considered primarily as an anti-cancer drug. Data available until 31th of May, 2020 at Clinicaltrials.gov and PubMed have been reviewed. EXPERT OPINION: The failure of 4-Cl-KYN for use as an anti-depressant may be related to inadequate concentration, or that the ketamine-like rapid anti-depressant effect is not produced via NMDAR modulation. Further clarification may emerge from studies involving higher drug concentration, and/or from identification of ketamine targets....
Source: Expert Opinion on Investigational Drugs - Category: Drugs & Pharmacology Tags: Expert Opin Investig Drugs Source Type: research