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ML-180 (SR1848)

  Cat. No.:  DC39003   Featured
Chemical Structure
863588-32-3
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More than 5000 active chemicals with high quality for research!
Field of application
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.
Cas No.: 863588-32-3
Chemical Name: 6-[4-(3-chlorophenyl)-1-piperazinyl]-3-cyclohexyl-2,4(1h,3h)-pyri Midinedione
Synonyms: ML180;ML 180;SR-1848;SR 1848;SR1848
SMILES: ClC1=CC=CC(N2CCN(C3NC(=O)N(C4CCCCC4)C(=O)C=3)CC2)=C1
Formula: C20H25ClN4O2
M.Wt: 388.891103506088
Purity: >98%
Sotrage: 2 years -20°C Powder, 2 weeks 4°C in DMSO, 6 months -80°C in DMSO
Publication: [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.
Description: 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].
Target: IC50: 3.7 μM (LRH-1)[1]
In Vivo: 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.
In Vitro: 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.
References: [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.
MSDS
COA
LOT NO. DOWNLOAD
2018-0101
2018-0101
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