MDR-652 / Medifron - LARVOL DELTA

Three-Dimensional Quantitative Structure-Activity Relationship Study of Transient Receptor Potential Vanilloid 1 Channel Antagonists Reveals Potential for Drug Design Purposes. (PubMed, Int J Mol Sci) - "Starting from previously designed compounds, derived from the hybridization of antagonist SB-705498 and partial agonist MDR-652, we performed a virtual screening on a pharmacophore model built by exploiting the Cryo-EM 3D structure of a nanomolar antagonist in complex with the human TRPV1 channel. Again, we determined the compounds' binding poses after alignment to the pharmacophoric model, and we predicted their inhibition rates with the validated 3D-QSAR model. The obtained values resulted in being even more promising than parent compounds, demonstrating that ongoing research still leaves much room for improvement."

Journal • Pain

Medipron “Phase 1 clinical trial results for topical non-narcotic analgesics, excellent tolerability” [Google translation] (eDaily) - P1 | N=NA | "Medipron (065650) , topical non-narcotic analgesic (1% MDR-652 gel) clinical trial results (CSR) 'MDR-652 and its metabolites are The degree of exposure in the body is very slight, so there is no systemic effect, and the tolerability is judged to be excellent even in the evaluation of local adverse reactions.'"

P1 data • CNS Disorders • Diabetic Neuropathy • Pain • Peripheral Neuropathic Pain

Medifron begins phase 1 clinical trial for non-narcotic analgesics…“Starting to enter the global market” [Google translation] (E-Today) - "Medifron announced that it will start a phase 1 clinical trial of a topical non-narcotic analgesic (1% MDR-652 gel) on the 9th. In June 2020, the Ministry of Food and Drug Safety received approval for clinical trials and was preparing for clinical trials, but it was delayed for about two years due to the novel coronavirus infection (COVID-19) pandemic that occurred afterwards. This clinical trial is conducted at Hallym University Sacred Heart Hospital, and under the guidance of Professor Donghwan Lee, 1% MDR-652 gel is evaluated for stability, tolerability, and systemic exposure characteristics after transdermal single and repeated administration. Randomization, placebo-controlled, double-blind, and maximal usage evaluation will be used as evaluation methods."

New P1 trial • CNS Disorders • Diabetic Neuropathy • Pain • Peripheral Neuropathic Pain

Discovery of (S)-N-(3-isopropylphenyl)-2-(5-phenylthiazol-2-yl)pyrrolidine-1-carboxamide as potent and brain-penetrant TRPV1 antagonist. (PubMed, Eur J Med Chem) - "In this work, in order to develop potent, CNS-penetrant, and orally available TRPV1 antagonists, three series of novel molecules based on the key pharmacophore structures of classic TRPV1 ligands SB-705498 and MDR-652 were designed and synthesized. Molecular docking and dynamics studies indicated that the high binding affinity of compound 7q to TRPV1 was related to multiple interactions, which resulted in significant conformational changes of TRPV1. Overall, our findings have led to a potent, mode-selective, and CNS-penetrant TRPV1 antagonist as a valuable lead for development of novel TRPV1 antagonists."

Journal • Pain