Nigakinone

Nigakinone is an orally active FXR agonist and NLRP3 inhibitor. Nigakinone suppresses bile acid-induced inflammation and cell damage, regulates the bile acid profile, and alleviates intestinal mucosal barrier injury. Nigakinone synergizes with Irinotecan (HY-16562) to inhibit the proliferation and migration of colorectal cancer cells as well as the growth of subcutaneous xenograft tumors. Nigakinone can be used in research related to ulcerative colitis and colorectal cancer^[1][2]. In Vitro:Nigakinone (10 μM; 24 h) functionally activates hFXR in HEK293T cells and significantly enhances BSEP promoter activity in an hFXR-dependent manner^[1].
Nigakinone (0.2-5 μM; 24 h) alleviates Lithocholic acid (LCA) (HY-B0172)-induced inflammatory responses and tight junction damage in CT26 cells by activating FXR, and this effect is abolished in FXR-silenced cells^[1].
Nigakinone (0.2-5 μM) significantly upregulates the expression of FXR protein in HCT116 colon cancer cells with low FXR expression^[2].
Nigakinone (0.2-5 μM) significantly upregulates the expression of FXR protein in FXR-low-expressing Caco-2 colorectal cancer cells^[2].
As an FXR agonist, nigakinone induces concentration-dependent upregulation of FXR downstream target genes FGF19 and SHP in FXR-low-expressing HCT116 colorectal cancer cells^[2].
Nigakinone acts as an FXR agonist in HT-29 colon cancer cells with high FXR expression, and significantly upregulates FGF19 and SHP, the downstream target genes of FXR^[2].
Nigakinone (0.2-5 μM; 48 h) synergistically inhibits the viability of HCT116, Caco-2, and HT-29 siFXR colorectal cancer cells with low FXR expression^[2].
Nigakinone (1 μM; 24 h, 48 h) synergistically inhibits the migration of HCT116, Caco-2, and HT-29 siFXR colorectal cancer cells with low FXR expression, in combination with Irinotecan^[2].
Nigakinone (1 μM; 48 h) acts synergistically with Irinotecan to inhibit the clonogenic activity of HCT116 and Caco-2 colorectal cancer cells with low FXR expression^[2]. In Vivo:Nigakinone (25-100 mg/kg; p.o.; daily; for 9 consecutive days) alleviates DSS (HY-116282C)-induced ulcerative colitis in SD rats by activating FXR to reduce inflammation, protect the intestinal mucosal barrier and regulate bile acid homeostasis^[1].
Nigakinone (60 mg/kg; p.o.; once daily; for 9 consecutive days) alleviates dextran sulfate sodium (DSS)-induced ulcerative colitis in wild-type C57BL/6 mice by inhibiting NLRP3-mediated inflammatory responses, protecting the intestinal mucosal barrier, and regulating the enterohepatic circulation of bile acids via activation of FXR^[1].
Nigakinone (60 mg/kg; p.o.; once daily; for 9 consecutive days) fails to alleviate dextran sulfate sodium (DSS)-induced ulcerative colitis in FXR-knockout C57BL/6N mice, confirming that FXR is an essential prerequisite for nigakinone to exert its therapeutic effect on colitis^[1].
Nigakinone (35 mg/kg; i.p.; once daily; for 21 consecutive days) alone inhibits the growth of colorectal cancer xenografts by upregulating FXR; when combined with Irinotecan, it exerts synergistic antitumor activity, enhancing the inhibition of cell proliferation and inducing apoptosis^[2].