MK-7246 / Merck (MSD) - LARVOL DELTA

[F]MK-7246 for Positron Emission Tomography Imaging of the Beta-Cell Surface Marker GPR44. (PubMed, Pharmaceutics) - "Preclinical assessments demonstrated the strong affinity and selectivity of [F]MK-7246 towards GPR44. Additionally, [F]MK-7246 exhibited excellent metabolic stability, a fast clearance profile from blood and tissues, qualifying it as a promising radioactive probe for GPR44-directed PET imaging."

Journal • Diabetes • Metabolic Disorders

PET Imaging of GPR44 by Antagonist [C]MK-7246 in Pigs. (PubMed, Biomedicines) - "The binding could be blocked by preadministration of nonradioactive MK-7246, indicating a receptor-binding mechanism. [C]MK-7246 showed strong potential as a PET ligand candidate for visualization of beta-cell mass (BCM) and clinical translation of this methodology is ongoing."

Journal • Diabetes • Metabolic Disorders

Design and application of intramolecular vinylogous Michael reaction for the construction of 2-alkenyl indoles. (PubMed, Chem Commun (Camb)) - "A one-pot N-allylation of ortho-tosylamidocinnamates/congeners with γ-bromocrotonates followed by intra-VMA has been described to provide access to a diverse range of 2-alkenyl indole derivatives in reasonable to high yields. The synthetic value of the developed intra-VMA has been demonstrated by gram-scale synthesis of a representative indole derivative and also by the formal synthesis of MK-7246: a Merck's clinical CRTH2 antagonist."

Journal

CRTH2 antagonist MK-7246: A synthetic evolution from discovery through development (J Org Chem) - Development of different synthetic routes to MK-7246 designed by Process Chemistry group are reported

Preclinical-other

Synthesis and preclinical evaluation of the CRTH2 antagonist [C]MK-7246 as a novel PET tracer and potential surrogate marker for pancreatic beta-cell mass. (PubMed, Nucl Med Biol) - "Initial preclinical in vitro and in vivo evaluations of [C]MK-7246 show binding and biodistribution properties suitable for PET imaging of CRTH2. Further studies are warranted to assess its potential in β-cell mass imaging and CRTH2 drug development."

Journal

GPR44 as a Target for Imaging Pancreatic Beta-Cell Mass. (PubMed, Curr Diab Rep) - "C-AZ12204657 and C-MK-7246 displayed a dose-dependent and GPR44-mediated binding to beta cells both in vitro and in vivo, with negligible uptake in exocrine pancreas. GPR44 represents an attractive target for visualization of BCM. Further progress in radioligand development including clinical testing is expected to clarify the role of GPR44 as a surrogate marker for BCM in humans."

Journal • Review