Phenotypic discovery of SB1501, an anti-obesity agent via modulating mitochondrial activities.

Phenotypic discovery of SB1501, an anti-obesity agent via modulating mitochondrial activities. ChemMedChem. 2021 Feb 03;: Authors: Jo A, Kim M, Kim JI, Ha J, Hwang YS, Nam H, Hwang I, Kim JB, Park SB Abstract Obesity has become a pandemic that threatens the quality of life and discovering novel therapeutic agents that can reverse obesity and obesity-related metabolic disorders are necessary. Here, we aimed to identify new anti-obesity agents using a phenotype-based approach. We performed image-based high-content screening with a fluorogenic bioprobe (SF44), which visualizes cellular lipid droplets (LDs), to identify initial hit compounds. A structure-activity relationship study led us to yield a bioactive compound SB1501, which reduces cellular LDs in 3T3-L1 adipocytes without cytotoxicity. SB1501 induced the expression of gene products that regulate mitochondrial biogenesis and fatty acid oxidation in 3T3-L1 adipocytes. Daily treatment with SB1501 improved the metabolic states of db/db mice by reducing body fat mass, adipose tissue mass, food intake, and increasing glucose tolerance. The anti-obesity effect of SB1501 may result from perturbation of the PGC-1α-UCP1 regulatory axis in inguinal white adipose tissue and brown adipose tissue. These data suggest the therapeutic potential of SB1501 as an anti-obesity agent via modulating mitochondrial activities. PMID: 33538065 [PubMed - as supplied by publisher]
Source: ChemMedChem - Category: Chemistry Authors: Tags: ChemMedChem Source Type: research