Category Ranking
98%
Total Visits
921
Avg Visit Duration
2 minutes
Citations
20
Article Abstract
We report the discovery of a novel series of DGAT1 inhibitors in the benzimidazole class with a piperdinyl-oxy-cyclohexanecarboxylic acid moiety. This novel series possesses significantly improved selectivity against the A2A receptor, no ACAT1 off-target activity at 10 μM, and higher aqueous solubility and free fraction in plasma as compared to the previously reported pyridyl-oxy-cyclohexanecarboxylic acid series. In particular, 5B was shown to possess an excellent selectivity profile by screening it against a panel of more than 100 biological targets. Compound 5B significantly reduces lipid excursion in LTT in mouse and rat, demonstrates DGAT1 mediated reduction of food intake and body weight in mice, is negative in a 3-strain Ames test, and appears to distribute preferentially in the liver and the intestine in mice. We believe this lead series possesses significant potential to identify optimized compounds for clinical development.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4207266 | PMC |
| http://dx.doi.org/10.1021/ml5003426 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Exploring allosteric properties of mammalian ALOX15: octyl (-(4-(benzofuran-2-yl)-2-methoxyphenyl)sulfamoyl)- and octyl (-(4-(1-indol-2-yl)-2-methoxyphenyl)sulfamoyl)carbamates as ALOX inhibitors.
RSC Adv
September 2025
Departament de Química, Universitat Autònoma de Barcelona Bellaterra 08193 Barcelona Spain
Mammalian ALOX15 are allosteric enzymes but the mechanism of allosteric regulation remains a matter of discussion. Octyl (-(5-(1-indol-2-yl)-2-methoxyphenyl)sulfamoyl)carbamate inhibits the linoleate oxygenase activity of ALOX15 at nanomolar concentrations, but oxygenation of arachidonic acid is hardly affected. The mechanism of substrate selective inhibition suggests inter-monomer communication within the allosteric ALOX15 dimer complex, in which the inhibitor binding to monomer A induces conformational alterations in the structure of the active site of monomer B.
View Article and Find Full Text PDFStructural analysis of stereoselective galactose pyruvylation toward the synthesis of bacterial capsular polysaccharides.
Beilstein J Org Chem
August 2025
Institute of Chemistry, Academia Sinica, Taipei 115, Taiwan.
Pyruvate ketal is a biologically essential moiety due to its key role as an intermediate in metabolic pathways, serving as a key precursor for the synthesis of various essential biomolecules in organisms. However, the / stereochemistry of pyruvate ketal is difficult to control through chemical methods. In this study, the acid-labile pyruvate ketal linked to the 4- and 6-positions of galactose was cautiously constructed, and the X-ray analysis of the -configured product was successfully obtained.
View Article and Find Full Text PDFTherapeutic Power of Date Fruit ( L.): A Nutrient-Rich Superfood for Holistic Health and Disease Prevention.
Food Sci Nutr
September 2025
Panvascular Diseases Research Center, Quzhou People's Hospital The Quzhou Affiliated Hospital of Wenzhou Medical University Quzhou China.
Date fruit ( L.) is a highly nutritious and therapeutic food with substantial potential to improve human health. This review emphasizes the nutritional and therapeutic traits of date fruit, focusing on its role as a functional food and dietary supplement.
View Article and Find Full Text PDFImpact of Albumin-Binding Moieties on Structure-Affinity-Pharmacokinetic Relationships of Novel FAP-Targeting Radioligands.
Mol Pharm
September 2025
Department of Patho-Functional Bioanalysis, Graduate School of Pharmaceutical Sciences, Kyoto University, 46-29 Yoshida Shimoadachi-cho, Sakyo-Ku, Kyoto 606-8501, Japan.
Fibroblast activation protein (FAP) is an attractive biomarker for tumor-targeting radioligands. While [Ga]Ga-FAPI-46 is a promising FAP-targeting radioligand for cancer diagnosis, clinical application of [Lu]Lu-FAPI-46 for targeted radionuclide therapy is limited due to its insufficient tumor retention. Albumin binder (ALB) including 4-(-iodophenyl)butyric acid is widely utilized to improve tumor accumulation of radioligands.
View Article and Find Full Text PDFPoly (ADP-ribose) polymerase in yeasts: characterization and involvement in telomere maintenance.
Nucleic Acids Res
September 2025
Department of Genetics, Comenius University Bratislava, Faculty of Natural Sciences, Ilkovičova 6, 842 15 Bratislava, Slovakia.
Poly (ADP-ribose) polymerases (PARPs) are enzymes catalyzing the post-translational addition of chains of ADP-ribose moieties to proteins. In most eukaryotic cells, their primary protein targets are involved in DNA recombination, repair, and chromosome maintenance. Even though this group of enzymes is quite common in both eukaryotes and prokaryotes, no PARP homologs have been described so far in ascomycetous yeasts, leaving their potential roles in this group of organisms unexplored.
View Article and Find Full Text PDF