ML-180

ML-180 (SR1848) is a potent orphan nuclear receptor liver receptor homolog 1 (LRH-1; NR5A2) inverse agonist with an IC50 of 3.7 µM. ML-180 is inactive for steroidogenic factor-1 (SF-1; NR5A1; IC50>10 µM). ML-180 has the potential for LRH-1-dependent cancers[1][2].

Research Areas >> Cancer

Signaling Pathways >> Others >> Others

IC50: 3.7 µM (LRH-1)[1]

ML-180 (SR1848; 0.01-100 µM; 48 hours) shows diminished capacity to proliferate at concentrations above 1 μM, and the EC50 being roughly 2.8 μM in Huh-7 cells. ML-180 inhibits cell proliferation in an LRH-1-dependent manner[2]. ML-180 (0.5-5 µM; 24 hours) shows a significant inhibition of cyclin-D1 and cyclin-E1 expression in hepatic cells, but has little effect on repression in SK-OV-3 cells[2]. ML-180 (5 µM; 24 hours) leads to a rapid decrease of LRH-1 expression and efficiently represses endogenous LRH-1 signaling[2]. ML-180 (0.5-5 µM; 24 hours) inhibits LRH-1 mRNA expression in a dose-dependent manner[2]. ML-180 (5 μM; 2 hours) rapidly and significantly decreases the mRNA levels of LRH-1 receptor and its downstream targets (CYP19, GATA3, and GATA4) in Huh-7 and HepG2 cells[2]. Cell Proliferation Assay[2] Cell Line: Huh-7 cells Concentration: 0.01, 0.1, 1, 10, 100 µM Incubation Time: 48 hours Result: Showed diminished capacity to proliferate at concentrations above 1 μM. Cell Cycle Analysis[2] Cell Line: Huh-7 cells Concentration: 0.5, 1, 5 µM Incubation Time: 24 hours Result: Showed a significant inhibition of cyclin-D1 and cyclin-E1 expression in hepatic cells. Western Blot Analysis[2] Cell Line: Huh-7 cells Concentration: 5 µM Incubation Time: 24 hours Result: Significantly reduced the LRH-1 protein levels. RT-PCR[2] Cell Line: Huh-7 cells Concentration: 0.5, 1, 5 µM Incubation Time: 24 hours Result: Inhibited LRH-1 mRNA expression in a dose-dependent manner.

ML-180 (SR1848; 30 mg/kg; i.p.; daily; for 10 days) has a statistically significant decrease of both LRH-1 and SHP mRNA in adrenal glands and pancreatic tissue[2]. Animal Model: 8-week-old C57Bl/6J mice[2] Dosage: 30 mg/kg Administration: IP; daily; for 10 days Result: Had a statistically significant decrease of both LRH-1 and SHP mRNA in adrenal glands and pancreatic tissue.

[1]. Busby S, et al. Discovery of Inverse Agonists for the Liver Receptor Homologue-1 (LRH1; NR5A2).

[2]. Corzo CA, et al. Antiproliferation activity of a small molecule repressor of liver receptor homolog 1. Mol Pharmacol. 2015 Feb;87(2):296-304.