@article{ref1,
title="Progress in the development of kynurenine and quinoline-3-carboxamide-derived drugs",
journal="Expert opinion on investigational drugs",
year="2020",
author="Boros, Fanni and Vécsei, László",
volume="29",
number="11",
pages="1223-1247",
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 the preclinical and clinical use of a KP metabolite analog 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-carboxamide 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 31 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. Clinical application trials in very diverse indications of structurally related quinoline-3-carboxamides and the wide range of their mode of action warrant further studies permitting direct comparison of effects and better target identification.<p /><p>Language: en</p>",
language="en",
issn="1354-3784",
doi="10.1080/13543784.2020.1813716",
url="http://dx.doi.org/10.1080/13543784.2020.1813716"
}