In:
Current Radiopharmaceuticals, Bentham Science Publishers Ltd., Vol. 10, No. 1 ( 2017-04), p. 35-40
Abstract:
Background and Objective: Melanin-concentrating hormone (MCH) is an attractive target
for antiobesity agents and many drug discovery programs have been dedicated to identify smallmolecule antagonists of melanin-concentrating hormone receptor 1 (MCHR1). The aim of this study
was to develop a positron emission tomography (PET) tracer for MCHR1 for translation of preclinical pharmacology to clinic to enhance success rate of drug discovery programs. Methods: We identified 4-(cyclopropylmethoxy)-N-[8-methyl-3-({[(1-methyl-1H-pyrrol-2-yl)methyl]
amino}ethyl)quinolin-7-yl] benzamide (Compound II) from Takeda MCHR1 antagonist library by
utilizing binding affinity, log D value, physicochemical parameters ideal for a central nerve system agent, and synthetic feasibility of corresponding carbon-11 labeled radioligands as selection parameters
for tracer candidates. Results: In the rat PET study, [11C] Compound II showed clear uptake in the caudate/putamen with the pretreatment of cyclosporine A and its uptake was higher than that in the cerebellum where expression
of MCHR1 was reported to be low. Conclusion: In summary, [11C]Compound II is a promising lead compound for developing a suitable MCHR1 PET radioligand. [11C]Compound II, in combination with cyclosporine A, could be used as a research tool to visualize and quantify MCHR1 in rodents.
Type of Medium:
Online Resource
ISSN:
1874-4710
DOI:
10.2174/1874471009666161230113630
Language:
English
Publisher:
Bentham Science Publishers Ltd.
Publication Date:
2017
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