SPA70

SPA70 is an orally available, selective, competitive antagonist of the human pregnane X receptor (hPXR) (IC₅₀=540 nM), which blocks the hPXR nuclear receptor signaling pathway and its mediated transcriptional activation of drug metabolizing enzymes (e.g., CYP3A4, MDR1). SPA70 exhibits low toxicity in both in vitro and in vivo models and can be used to study hPXR-mediated cancer drug resistance and liver injury^[1][2][3]. IC50 & Target:IC50: 540 nM (hPXR)^[1] In Vitro:TR-FRET binding assay: SPA70 competitively inhibits the binding of hPXR to its ligand with an IC50 of 540 nM (hPXR TR-FRET binding assay, 30 min)^[1].
Cytotoxicity assay: SPA70 (10 μM; 24 h, 72 h) shows low toxicity in HepG2, HEK293 and Hepa 1-6 cells^[1].
Migration/invasion assay: SPA70 (10 μM; 72 h) significantly inhibits the migration and invasion ability of A549/TR and H460/TR cells^[2].
Cell reporter gene assay: SPA70 (10 μM; 24 h) significantly inhibits hPXR-mediated transcriptional activation of CYP3A4 and MDR1^[2].
In Vivo:SPA70 (200 mg/kg; i.p.; once a day for 3 days) significantly inhibits Rifampicin (HY-B0272)-induced Cyp3a11 expression, prolongs anesthetic metabolism time, and alleviated liver injury in hPXR transgenic mice^[1].
SPA70 (30 mg/kg; i.p.; 3 times a week for 4 weeks) significantly inhibits tumor growth (TGI=89.5%) and reduces P-gp, PXR, and Tip60 expression in the A549/TR xenograft model^[2].
SPA70 (150 mg/kg; i.p.; once daily for 3 days) effectively blocks Rifampicin (HY-B0272)-induced CYP3A4 expression and alleviats hemorrhagic shock-induced liver injury and oxidative stress in hPXR/CYP3A4 humanized mice^[1][3].