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| Targets |
Nidufexor targets the farnesoid X receptor (FXR), a nuclear receptor that regulates bile acid, lipid, and glucose metabolism. It acts as a partial agonist, activating FXR to modulate gene expression. FXR activation leads to reduced bile acid synthesis, improved insulin sensitivity, and decreased hepatic steatosis. This mechanism underlies its therapeutic potential in NASH. The compound is a non-bile acid FXR agonist.
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| ln Vitro |
In vitro, Nidufexor shows partial FXR agonistic activity in biochemical assays. In FXR-HTRF assays measuring FXR-SRC1 interaction, it has an EC₅₀ of 7 nM. The compound activates FXR-dependent gene modulation in cell-based reporter assays. It is a potent and selective FXR agonist. Detailed in vitro data are available in the primary literature. Nidufexor demonstrates favorable in vitro properties for drug development.
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| ln Vivo |
Nidufexor (LMB763), in a mouse model of non-alcoholic steatosis (NASH), is a strong and circumferential in vivo FXR gene modulator that decreases fibrosis, inflammation, and steatosis [1]. Partitioning time (t1/2) following moderate Cmax values (4.5, 12.4, 28.1, 80.9, and 140.8 μM) and powder formulations (3, 10, 30, 100, and 300 mg/kg) in structures (aged roughly 10 weeks); 3.9 5.7 6.3 5.6 6.3 h) [1] Nidufexor exhibits distinct half-lives (attention 4.5, adsorption 4.4 and dog 6.8 hours) in animal models following topical studies (attention 3.0, adsorption 5.0 and dog 0.5 mg/kg): Han-Wistar rats[1].
In vivo, Nidufexor shows FXR-dependent gene modulation. It has been evaluated in animal models of NASH and diabetic nephropathy. The compound is orally bioavailable and has advanced to Phase 2 human clinical trials. Efficacy data from preclinical studies support its development for NASH. The compound's in vivo effects on lipid metabolism, liver histology, and fibrosis have been characterized. |
| Enzyme Assay |
In vitro FXR activation assays for Nidufexor typically use fluorescence resonance energy transfer (FRET) or time-resolved FRET (TR-FRET) technology. Recombinant FXR ligand-binding domain (LBD) and fluorescently labeled SRC1 peptide are incubated with varying concentrations of Nidufexor in assay buffer (50 mM Tris-HCl, pH 7.5, 50 mM KCl, 2 mM DTT, 0.01% Tween-20). The signal is measured after incubation at room temperature for 1-2 hours. EC₅₀ values are calculated from dose-response curves. Controls include DMSO vehicle and a reference FXR agonist (e.g., GW4064).
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| Cell Assay |
For cell-based assays, cells expressing FXR (e.g., HepG2 or HEK-293 transfected with FXR) are cultured in DMEM with 10% charcoal-stripped FBS. Cells are seeded in 96-well plates and treated with Nidufexor at various concentrations for 24 hours. FXR target gene expression (e.g., SHP, BSEP) is measured by RT-PCR or reporter assays. Cell viability is assessed by MTT or CellTiter-Glo. All treatments include vehicle controls and are performed in triplicate.
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| Animal Protocol |
Animal/Disease Models: Han-Wistar rats[1]
Doses: 0.1, 0.3, 1.5, 7.5, 25, 100 mg/kg (pharmacokinetic/PK/PK Analysis) Route of Administration: po (oral gavage), one time/day for 14 days Experimental Results:On day 1 and 13, serum exposure increased approximately dose-proportionally from 0.1 to 100 mg/kg. Exposure at 0.1 and 0.3 mg/kg was likely underestimated on day 13. No significant accumulation was observed[1]. In vivo, Nidufexor is typically administered orally to rodents or used in clinical trials. For preclinical studies, mice or rats are dosed at various regimens. Endpoints include liver histology (steatosis, inflammation, fibrosis), serum ALT/AST levels, bile acid profiles, and lipid panels. Pharmacodynamic markers (FXR target gene expression) are measured in liver tissue. Pharmacokinetic parameters are determined from plasma samples. Clinical trials follow standard protocols for Phase 2 studies. |
| ADME/Pharmacokinetics |
Nidufexor (LMB-763) is an orally bioavailable FXR partial agonist. It has a favorable pharmacokinetic profile supporting once-daily dosing. The compound has advanced to Phase 2 clinical trials. Detailed pharmacokinetic parameters (bioavailability, half-life, Cmax, AUC) are available from clinical study reports. The compound is metabolized by hepatic enzymes. It is designed for the treatment of NASH and hepatobiliary diseases.
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| Toxicity/Toxicokinetics |
Nidufexor has undergone preclinical and clinical toxicology evaluation as part of its development program. The compound has advanced to Phase 2 clinical trials, indicating an acceptable safety profile in early studies. Detailed safety data are available from clinical study reports. The compound is for clinical research use and is not approved for general use.
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| References | |
| Additional Infomation |
Nidufexor is being studied in the clinical trial NCT03804879 (safety, tolerability and efficacy of LMB763 in patients with diabetic nephropathy).
Nidufexor (LMB-763) is an FXR agonist under clinical development for NASH and hepatobiliary diseases. It has advanced to Phase 2 clinical trials. The compound is a non-bile acid partial FXR agonist. Its mechanism involves FXR activation and modulation of bile acid, lipid, and glucose metabolism. The compound is available for research purposes from chemical suppliers. |
| Molecular Formula |
C27H22CLN3O4
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|---|---|
| Molecular Weight |
487.94
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| Exact Mass |
487.129
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| CAS # |
1773489-72-7
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| Related CAS # |
1773489-72-7;
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| PubChem CID |
118063735
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| Appearance |
White to off-white solid powder
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| Density |
1.4±0.1 g/cm3
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| Boiling Point |
781.1±60.0 °C at 760 mmHg
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| Flash Point |
426.2±32.9 °C
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| Vapour Pressure |
0.0±2.8 mmHg at 25°C
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| Index of Refraction |
1.671
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| LogP |
3.72
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
5
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| Rotatable Bond Count |
6
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| Heavy Atom Count |
35
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| Complexity |
755
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| Defined Atom Stereocenter Count |
0
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| InChi Key |
JYTIXGYXBIBOMN-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C27H22ClN3O4/c1-30-25-21-13-20(28)11-12-23(21)35-16-22(25)24(29-30)26(32)31(14-17-5-3-2-4-6-17)15-18-7-9-19(10-8-18)27(33)34/h2-13H,14-16H2,1H3,(H,33,34)
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| Chemical Name |
4-[(N-benzyl-8-chloro-1-methyl-1,4-dihydro[1]benzopyrano[4,3-c]pyrazole-3-carboxamido)methyl]benzoic acid
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| Synonyms |
LMB 763 LMB-763 LMB763
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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) |
DMSO : ~83.33 mg/mL (~170.78 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (4.26 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.08 mg/mL (4.26 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.0494 mL | 10.2472 mL | 20.4943 mL | |
| 5 mM | 0.4099 mL | 2.0494 mL | 4.0989 mL | |
| 10 mM | 0.2049 mL | 1.0247 mL | 2.0494 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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