MK-3207 / Merck (MSD) - LARVOL DELTA

Identifying drug targets and evaluating KLK3-targeted inhibitors for prostate cancer using in-silico and in-vitro approaches. (PubMed, Med Oncol) - "MM-GBSA analysis revealed strong binding energy (- 75.57 to - 66.36 kcal/mol) and consistent ligand efficiency. This study bridges computational drug discovery and phytochemical analysis, nominating Curcuma longa derivatives and MK3207 as promising KLK3 inhibitors for PC therapy."

Journal • Preclinical • Genito-urinary Cancer • Oncology • Pain • Prostate Cancer • Solid Tumor • KLK3

Structure-based design of Mycobacterium tuberculosis PptT-ACP complex inhibitors using derivative design and machine learning. (PubMed, Folia Microbiol (Praha)) - "Predicted biological activity using machine learning (Random Forest Regression) indicated pIC50 values of 25.64, 22.43, 22.32, and 26.26 for Compound_36, Compound_98, Compound_60, and Mk3207, respectively. This study demonstrates the potential of derivative design and machine learning in designing potent MTB inhibitors, providing strong candidates for experimental validation to combat drug-resistant TB effectively."

Journal • Infectious Disease • Pulmonary Disease • Respiratory Diseases • Tuberculosis

Calcitonin gene-related peptide (CGRP) exerts membrane, cellular and synaptic actions on serotonergic dorsal raphe neurons ex vivo: Functional implications for a role in dorsal raphe-controlled functions. (PubMed, Neuropharmacology) - "In contrast, the CGRP receptor antagonist MK-3207 blocked the effects on outward current and attenuated the action of CGRP on reducing intracellular calcium. Despite inhibitory membrane and synaptic effects, no change was noted in firing rate. Our findings raise the intriguing possibility that the CGRP system plays a role in mediating limbic-controlled behaviors, at least in part, through direct actions on serotonergic DR neurons, however the effect of CGRP on DR 5-HT output remains to be investigated."

Journal • Preclinical • CNS Disorders • Depression • Migraine • Mood Disorders • Pain • Psychiatry

Structure-based virtual screening and drug repurposing studies indicate potential inhibitors of bovine papillomavirus E6 oncoprotein. (PubMed, Microbiol Immunol) - "Our results reveal that Lumacaftor and MK-3207 are promising candidates for controlling BPV1 infection. The findings of this study may contribute to the development of E6 oncoprotein blockers in an accelerated and cost-effective manner."

Journal • Infectious Disease • Oncology

From Proteome to Potential Drugs: Integration of Subtractive Proteomics and Ensemble Docking for Drug Repurposing against Pseudomonas aeruginosa RND Superfamily Proteins. (PubMed, Int J Mol Sci) - "Our findings confirm the critical role of RND efflux pumps in antibiotic resistance and suggest that MK-3207, R-428, and Suramin could be effectively repurposed to target these proteins. This approach highlights the potential of drug repurposing as a viable strategy to combat P. aeruginosa infections."

Journal • Infectious Disease

Molecular docking analysis of FDA approved drugs with the glycoprotein from Junin and Machupo viruses. (PubMed, Bioinformation) - "Therefore, it is of interest to acquittance the molecular docking analysis data of FDA approved drugs with the glycoprotein from Junin and Machupo viruses for consideration in drug discovery. Thus, we report the optimal binding features of MK-3207 and Dihydro ergotamine with the protein target for further validation and consideration."

FDA event • Journal

Safety evaluation of oral calcitonin-gene-related peptide receptor antagonists in patients with acute migraine: a systematic review and meta-analysis. (PubMed, Eur J Clin Pharmacol) - "Despite oral CGRP receptor antagonists posing a significantly higher risk of AEs when compared to placebo, CGRP receptor antagonists have a favorable safety profile compared to triptans. Our findings inform strategies to enhance safety and tolerability in the treatment of acute migraine."

Journal • Retrospective data • Review • CNS Disorders • Fatigue • Migraine • Pain • Xerostomia

Gepants for abortive treatment of migraine: A network meta-analysis. (PubMed, Brain Behav) - "Gepants were effective for abortive treatment of migraine. The most effective treatment of gepants for migraine might be olcegepant which were administrated transvenously. And all of gepants were safe for migraine treatment with single dose."

Journal • Retrospective data • CNS Disorders • Migraine • Pain

The role of CGRP as targeted treatment for migraine - Introduction (YouTube) - "Stewart J. Tepper, MD, provides his perspectives on the clinical impact of 4 recently published studies involving the management of patients with migraines."

Video

Mechanistic Investigations Support Liver Safety of Ubrogepant. (PubMed, Toxicol Sci) - "In contrast, DILIsym predicted no hepatotoxicity during treatment with ubrogepant, even at daily doses up to 1000 mg (10-fold higher than the proposed clinical dose of 100 mg). These predictions are consistent with clinical trial experience showing that ubrogepant has lower potential to cause hepatotoxicity than has been observed with telcagepant and MK-3207."

Clinical • Journal • CNS Disorders • Migraine