ML-180

• CAT Number: R065005
• CAS Number: 863588-32-3
• Molecular Formula: C20H25ClN4O2
• Molecular Weight: 388.89
• Purity: ≥95%
• Synonyms: 6-[4-(3-chlorophenyl)piperazin-1-yl]-3-cyclohexyl-1H-pyrimidine-2,4-dione
• InChI: InChI=1S/C20H25ClN4O2/c21-15-5-4-8-17(13-15)23-9-11-24(12-10-23)18-14-19(26)25(20(27)22-18)16-6-2-1-3-7-16/h4-5,8,13-14,16H,1-3,6-7,9-12H2,(H,22,27)
• InChIKey: CHMQQIFPOIZPIJ-UHFFFAOYSA-N
• SMILES: C1CCC(CC1)N2C(=O)C=C(NC2=O)N3CCN(CC3)C4=CC(=CC=C4)Cl

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].
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].
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].

Reference

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

[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.
 [Content Brief]