Unknown

Dataset Information

0

GPBAR1 Activation by C6-Substituted Hyodeoxycholane Analogues Protect against Colitis.

ABSTRACT: GPBAR1 agonists have been identified as potential leads for the treatment of diseases related to colon inflammation such as Crohn's and ulcerative colitis. In this paper, we report the discovery of a small library of hyodeoxycholane analogues, decorated at C-6 with different substituents, as potent and selective GPBAR1 agonists. In vitro pharmacological assays showed that compound 6 selectively activates GPBAR1 (EC50 = 0.3 μM) and reduces the production of pro-inflammatory cytokines (IL-1β, IL-6, and TNF-α) in THP1 cells. The binding mode of compound 6 in GPBAR1 was elucidated by docking calculations. Moreover, compound 6 protects against TNBS-induced colitis in Gpbar1+/+ rodent model, representing an intriguing lead for the treatment of these inflammatory disorders.

SUBMITTER: Marino S 

PROVIDER: S-EPMC7236273 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature

Json Xml
altmetric image

Publications

GPBAR1 agonists have been identified as potential leads for the treatment of diseases related to colon inflammation such as Crohn's and ulcerative colitis. In this paper, we report the discovery of a small library of hyodeoxycholane analogues, decorated at C-6 with different substituents, as potent and selective GPBAR1 agonists. <i>In vitro</i> pharmacological assays showed that compound <b>6</b> selectively activates GPBAR1 (EC<sub>50</sub> = 0.3 μM) and reduces the production of pro-inflammato  ...[more]

Similar Datasets

Unknown De novo synthesis and biological evaluation of C6″-substituted C4″-amide analogues of SL0101.
| S-EPMC4251525 | biostudies-literature
Unknown Synthesis of C6-Substituted Purine Nucleoside Analogues via Late-Stage Photoredox/Nickel Dual Catalytic Cross-Coupling.
| S-EPMC8040254 | biostudies-literature
Unknown Glutathione peroxidase 8 negatively regulates caspase-4/11 to protect against colitis
| S-SCDT-EMM-2018-09386 | biostudies-other
Unknown Intestinal Sulfation Is Essential to Protect Against Colitis and Colonic Carcinogenesis.
| S-EPMC8238844 | biostudies-literature
Unknown Melatonin Analogues Potently Inhibit MAO-B and Protect PC12 Cells against Oxidative Stress.
| S-EPMC8533333 | biostudies-literature
Unknown Glutathione peroxidase 8 negatively regulates caspase-4/11 to protect against colitis.
| S-EPMC6949489 | biostudies-literature
Unknown Monotonous diets protect against acute colitis in mice: epidemiologic and therapeutic implications.
| S-EPMC4030530 | biostudies-literature
Unknown Novel C6-substituted 1,3,4-oxadiazinones as potential anti-cancer agents.
| S-EPMC4747355 | biostudies-literature
Unknown Fenretinide regulates macrophage polarization to protect against experimental colitis induced by dextran sulfate sodium.
| S-EPMC8806340 | biostudies-literature
Unknown Antibiotic Treatment Induces Long-lasting Changes in the Fecal Microbiota that Protect Against Colitis.
| S-EPMC5689073 | biostudies-literature