gut-restricted

Gut restricted-7 (GR-7) is a potent, covalent, orally administered, gut-selective bile salt hydrolase (BSH) inhibitor with tissue specificity that localizes to the gut. Gut restricted-7 reduces BSH activity in gut bacteria and decreases levels of unconjugated bile acids in mouse feces, making it suitable for research into metabolism, inflammation, and intestinal diseases.

PRMT5-IN-53 is an orally active, gut-restricted PRMT5 inhibitor, exhibiting pIC50 values of ≥ 9.7 against both hPRMT5 and mPRMT5. It binds to the PRMT5:MEP50 complex with a KD of 11.3 pM. In mice, PRMT5-IN-53 effectively inhibits intestinal PRMT5, significantly reducing both the number and size of polyps while avoiding systemic hematologic toxicity such as anemia and neutropenia. This compound is applicable in colorectal cancer research, particularly for familial adenomatous polyposis (FAP).

3-SucCA (3-Succinylated cholic acid), a bile acid derived from microbial sources, primarily functions as a lumen-restricted metabolite. It plays a crucial role in mitigating the progression of MAFL-MASH in mouse models by altering the gut microbiota composition, notably by enhancing the proliferation of Akkermansia muciniphila. Notably, lower levels of 3-sucCA have been observed in patients with biopsy-proven MAFLD.