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Purity: ≥98%
BMS-779788 (formerly known as XL-652, EXEL 04286652 and BMS-788) is a novel and potent LXR (Liver X Receptors) partial agonist with IC50 values of 68 nM for LXRα and 14 nM for LXRβ. BMS-779788 exhibits LXRβ selectivity with an improved therapeutic window in the cynomolgus monkey compared with a full pan agonist. BMS-779788 induced LXR target genes in blood in vivo with an EC50 = 610 nM, a value similar to its in vitro blood gene induction potency. BMS-779788 was 29- and 12-fold less potent than the full agonist T0901317 in elevating plasma triglyceride and LDL cholesterol, respectively, with similar results for plasma cholesteryl ester transfer protein and apolipoprotein B. However, ABCA1 and ABCG1 mRNA inductions in blood, which are critical for RCT, were comparable. Increased liver triglyceride was observed after 7-day treatment with BMS-779788 at the highest dose tested and was nearly identical to the dose response for plasma triglyceride, consistent with the central role of liver LXR in these lipogenic effects. Dose-dependent increases in biliary cholesterol and decreases in phospholipid and bile acid occurred in BMS-779788-treated animals, similar to LXR agonist effects reported in mouse. In summary, BMS-779788, a partial LXRβ selective agonist, has decreased lipogenic potential compared with a full pan agonist in cynomolgus monkeys, with similar potency in the induction of genes known to stimulate RCT. This provides support in nonhuman primates for improving LXR agonist therapeutic windows by limiting LXRα activity.
| ln Vitro |
In human whole blood, the ATP-binding transporters ABCA1 and ABCG1 were found to be strongly induced by the LXR selective partial agonist BMS-779788 (EC50=1.2 μM, 55% effectiveness) [2].
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| ln Vivo |
BMS-779788 has a similar potency to that of its in vitro blood gene induction when it comes to inducing LXR target genes in blood in vivo (EC50=610 nM). When it came to increasing plasma triglycerides and LDL cholesterol, BMS-779788 was shown to be 29 and 12 times less powerful than the full agonist T0901317, respectively. Similar results were observed for plasma cholesteryl ester transfer protein and apolipoprotein B [1]. BMS-779788 showed better induction than full agonists by peripherally inducing ABCA1 in mice at doses of 3 and 10 mpk without causing appreciable increases in plasma or liver triglycerides at these levels. circumstances [2].
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| References |
[1]. Kirchgessner TG, et al. Pharmacological characterization of a novel liver X receptor agonist with partial LXRα activity and a favorable window in nonhuman primates. J Pharmacol Exp Ther. 2015 Feb;352(2):305-14.
[2]. Kick E, et al. Liver X receptor (LXR) partial agonists: biaryl pyrazoles and imidazoles displaying a preference for LXRβ. Bioorg Med Chem Lett. 2015 Jan 15;25(2):372-7 |
| Molecular Formula |
C28H29CLN2O3S
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|---|---|
| Molecular Weight |
509.0595
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| CAS # |
918348-67-1
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| SMILES |
OC(C)(C)C1=CN(C2=CC=C(C3=CC=CC(S(=O)(C)=O)=C3)C=C2)C(C(C)(C4=CC=CC=C4Cl)C)=N1
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| InChi Key |
JLPURTXCSILYLW-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C28H29ClN2O3S/c1-27(2,23-11-6-7-12-24(23)29)26-30-25(28(3,4)32)18-31(26)21-15-13-19(14-16-21)20-9-8-10-22(17-20)35(5,33)34/h6-18,32H,1-5H3
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| Chemical Name |
2-(2-(2-(2-chlorophenyl)propan-2-yl)-1-(3'-(methylsulfonyl)-[1,1'-biphenyl]-4-yl)-1H-imidazol-4-yl)propan-2-ol
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| Synonyms |
XL-652; XL652; XL652; EXEL 04286652; EXEL04286652; EXEL-04286652; BMS-779788; BMS 779788; BMS779788; BMS-788; BMS 788; BMS788
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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 : ~100 mg/mL (~196.44 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: 2.5 mg/mL (4.91 mM) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), suspension solution; with sonication.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 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: ≥ 2.5 mg/mL (4.91 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 25.0 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 | 1.9644 mL | 9.8220 mL | 19.6440 mL | |
| 5 mM | 0.3929 mL | 1.9644 mL | 3.9288 mL | |
| 10 mM | 0.1964 mL | 0.9822 mL | 1.9644 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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