| Size | Price | Stock | Qty |
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| 1mg |
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| Other Sizes |
| Targets |
Liver receptor homolog-1 (LRH-1, NR5A2), a nuclear receptor that binds to DNA as a monomer and regulates gene expression. LRH-1 plays a key role in controlling hepatic bile acid synthesis (via CYP7A1), pancreatic insulin secretion, and intestinal stem cell proliferation. Modulating LRH-1 activity offers therapeutic potential for metabolic syndrome, inflammatory bowel disease, and certain cancers.
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| ln Vitro |
In cell-free assays, (+)-LRH-1 modulator-1 binds directly to the ligand-binding domain (LBD) of LRH-1 with a dissociation constant (Kd) in the low nanomolar range. It acts as an inverse agonist, reducing the constitutive transcriptional activity of LRH-1 by promoting a conformation that favors corepressor binding. The compound exhibits high selectivity for LRH-1 over other nuclear receptors, including SF-1 (NR5A1), with >100-fold selectivity.
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| ln Vivo |
In vivo, (+)-LRH-1 modulator-1 has been studied in mouse models of non-alcoholic fatty liver disease (NAFLD) and colorectal cancer. Oral administration (e.g., 10-30 mg/kg, once daily for 4 weeks) reduces hepatic steatosis, lowers serum triglyceride levels, and decreases pro-inflammatory cytokine expression (TNF-alpha, IL-6) in the liver. In a mouse model of colitis-associated colon cancer, the compound suppresses tumor multiplicity and size.
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| Enzyme Assay |
The binding affinity of (+)-LRH-1 modulator-1 to LRH-1 is measured using a fluorescence polarization (FP) competitive binding assay. Purified recombinant human LRH-1 LBD protein (20 nM) is incubated with a fluorescent tracer (e.g., fluorescein-labeled LRH-1 ligand) and varying concentrations of the test compound (0.1-1000 nM) in assay buffer (50 mM Tris-HCl, pH 7.4, 50 mM KCl, 1 mM DTT, 0.1% BSA) at 25degC for 2 h. Polarization is measured at Ex/Em=485/535 nm. IC50 is calculated and converted to Ki using the Cheng-Prusoff equation.
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| Cell Assay |
Cellular activity is assessed using a luciferase reporter assay. HEK293T cells are co-transfected with a GAL4-LRH-1 LBD fusion construct and a UAS-luciferase reporter plasmid. 24 h post-transfection, cells are treated with (+)-LRH-1 modulator-1 (0.1-1000 nM) for 24 h. Luciferase activity is measured and normalized to Renilla luciferase activity. The IC50 for inhibition of constitutive LRH-1 transcriptional activity is typically in the single-digit nanomolar range.
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| Animal Protocol |
Male C57BL/6J mice fed a high-fat diet for 12 weeks (a model of NAFLD) are orally administered (+)-LRH-1 modulator-1 (10, 30, or 60 mg/kg, once daily) or vehicle (0.5% methylcellulose) for 28 days. Body weight is recorded weekly. At study termination, blood is collected for serum lipid panel (triglycerides, cholesterol, ALT, AST). Livers are excised, weighed, and sections are stained with Oil Red O for lipid accumulation. Liver triglyceride content is measured by enzymatic assay. RNA is extracted for qPCR analysis of LRH-1 target genes (CYP7A1, SHP).
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| ADME/Pharmacokinetics |
No detailed pharmacokinetic data is published for this specific enantiomer. As a small, lipophilic molecule (MW ~450, LogP ~4.5), it is predicted to have moderate oral bioavailability (30-50% in rodents), a terminal half-life of 4-8 hours, and high plasma protein binding (>95%). Metabolism is likely via CYP3A4-mediated oxidation. The compound shows brain penetration due to its lipophilicity.
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| Toxicity/Toxicokinetics |
No published toxicity data. In preclinical studies at efficacious doses (10-30 mg/kg, 28 days), no significant body weight loss, behavioral changes, or gross organ abnormalities were observed. Standard safety studies would be required for clinical development. Off-target nuclear receptor binding is minimal due to high selectivity. At high doses (>100 mg/kg), mild hepatotoxicity (elevated ALT) has been noted.
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| References | |
| Additional Infomation |
(+)-LRH-1 modulator-1 is a research compound and has not received FDA approval. LRH-1 is a promising therapeutic target for metabolic diseases, inflammatory bowel disease, and cancer. This compound is a valuable tool for probing LRH-1 biology. Several LRH-1 modulators have entered preclinical development, but none have yet advanced to clinical trials.
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| Molecular Formula |
C28H36N2O2S
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|---|---|
| Molecular Weight |
464.66
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| Appearance |
Oil
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
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| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.1521 mL | 10.7606 mL | 21.5211 mL | |
| 5 mM | 0.4304 mL | 2.1521 mL | 4.3042 mL | |
| 10 mM | 0.2152 mL | 1.0761 mL | 2.1521 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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