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LP-856866

LP-856866 is an orally effective ACSL5 inhibitor with IC50 values of 8 nM and 4 nM for mouse and human ACSL5, respectively, and IC50 values of 6 nM and 17 nM for mouse and human ACSL1, respectively.
LP-856866
LP-856866 Chemical Structure Product category: GLP Receptor
This product is for research use only, not for human use. We do not sell to patients.
Official Supplier of:
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Product Description
LP-856866 is an orally effective ACSL5 inhibitor with IC50 values of 8 nM and 4 nM against ACSL5 in mice and humans, respectively, and 6 nM and 17 nM against ACSL1 in mice and humans, respectively. LP-856866 can delay gastric emptying, promote GLP-1 release, reduce food intake, decrease body weight and body fat percentage, maintain lean body mass, improve glucose homeostasis, enhance insulin sensitivity, reduce hepatic lipid accumulation, and lower serum triglyceride and total cholesterol levels. LP-856866 is suitable for research on diet-induced obesity.
Biological Activity I Assay Protocols (From Reference)
ln Vivo
LP-856866 (10-60 mg/kg/day; orally; continuously mixed into feed; 28 days) dose-dependently reduced body weight and body fat in male diet-induced obese mice while maintaining lean body mass and improving glucose tolerance and insulin sensitivity [1]. LP-856866 (orally; mixed into feed) reduced high-fat diet intake in wild-type mice but not Acsl5 knockout mice, confirming its targeted inhibitory effect on ACSL5 [1]. LP-856866 (75 mg/kg/day; orally; continuously mixed into feed; 11 days) altered the dietary preferences of male mice, reducing their preference for high-fat diets, decreasing total calorie intake, and preventing weight gain when they had free access to low-fat and high-fat diets [1]. LP-856866 (60 mg/kg/day; orally; continuously added to feed; 17 days) reduced liver triglyceride levels in male mice fed a high-fat diet [1]. LP-856866 (60 mg/kg/day; orally; continuously added to feed; 3 weeks) reduced serum total cholesterol and triglyceride levels in male mice fed a high-fat diet [1]. LP-856866 (60 mg/kg; orally; single pretreatment dose; 30 minutes before a high-fat meal) increased postprandial active GLP-1 levels in male mice and had a synergistic effect when used in combination with sitagliptin [1].
Animal Protocol
Animal/Disease Models:C57BL/6J-Tyrc−Brd X 129SvEvBrd hybrid mice (male; diet-induced obesity model, fed a 45% high-fat diet for more than 16 weeks after weaning) [1]
Doses: 10 mg/kg/day; 30 mg/kg/day; 60 mg/kg/day
Route of Administration: Oral; continuously mixed into feed; 28 days
Experimental Results: Compared with the vector control group, at 28 days, the weight and body fat of mice in each group were significantly reduced in a dose-dependent manner, while the reduction in lean body mass was less. In the oral glucose tolerance test (OGTT), compared with the vector control group, the blood glucose fluctuation at 30 minutes was significantly reduced in the 30 mg/kg/day and 60 mg/kg/day groups. In the oral glucose tolerance test (OGTT), compared with the vector control group, all treatment groups showed significantly reduced insulin fluctuations at 30 and 60 minutes. Compared with the vector control group, all treatment groups showed significantly improved homeostasis model assessment of insulin sensitivity index (HOMA-ISI) and composite insulin sensitivity index (Composite ISI).
Animal/Disease Models:C57BL/6J-Tyrc−Brd X 129SvEvBrd hybrid mice (male; fed standard diet, adapted to 10% low-fat diet for 2 weeks)[1]
Doses: 75 mg/kg/day
Route of Administration: Oral; continuously mixed into the diet; 11 days
Experimental Results: Compared with the vector control group, the experimental group mice had a significantly increased daily intake of 10% low-fat diet and a significantly decreased daily intake of 60% high-fat diet. Compared with the vector control group mice, the experimental group mice had a significantly reduced total calorie intake on day 1 and throughout the study period. Compared with the vector control group mice, the experimental group mice had a significantly reduced weight change during the 11-day study period compared with day 0.
Animal/Disease Models:C57BL/6J-Tyrc−Brd X 129SvEvBrd hybrid mice (male; fed Clinton 40% high-fat diet) [1]
Doses: 60 mg/kg/day
Route of Administration: Oral; continuous dietary supplementation; 17 days
Experimental Results: Compared with the vector-treated mice, liver triglyceride levels (measured in mg/liver and mg/g liver) were significantly reduced.
Animal/Disease Models:C57BL/6J-Tyrc−Brd X 129SvEvBrd hybrid mice (male; fed a 45% high-fat diet) [1]
Doses: 60 mg/kg/day
Route of Administration: Oral; continuous dietary supplementation; 3 weeks
Experimental Results: Compared with the vector-treated mice, serum total cholesterol and serum triglyceride levels were significantly reduced.
Animal/Disease Models:C57BL/6J-Tyrc−Brd X 129SvEvBrd hybrid mice (male; fed a 45% high-fat diet for at least 13 weeks) [1]
Doses: 60 mg/kg
Route of Administration: Oral; single pretreatment dose; 30 minutes before high-fat diet
Experimental Results: Plasma active glucagon-like peptide-1 (aGLP-1) levels were increased compared with the carrier treatment, peaking 5–10 minutes after the high-fat diet. When used in combination with sitagliptin, a synergistic effect was observed, with plasma aGLP-1 levels significantly higher than those of the carrier, sitagliptin alone, or LP-856866 alone at 5, 10, 15, 30, 60, 120, and 240 minutes after the high-fat diet.
References

[1]. Acyl-CoA Synthetase 5 Knockout and Inhibitors Protect Against Diet-Induced Obesity in Mice by Activating the Ileal Brake. J Endocr Soc. 2025;10(2):bvaf196. Published 2025 Nov 28.

These protocols are for reference only. InvivoChem does not independently validate these methods.
Physicochemical Properties
Appearance
White to light yellow solid
HS Tariff Code
2934.99.9001
Storage

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Note: 请将本产品存放在密封保护的环境中,避免受潮。
Shipping Condition
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
Solubility Data
Solubility (In Vitro)
DMSO : ~100 mg/mL (~191.74 mM; with sonication)
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
(e.g. IP/IV/IM/SC)
Injection Formulation 1: DMSO : Tween 80: Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution 50 μL Tween 80 850 μL Saline)
*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 : PEG300Tween 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).
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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)]
*Preparation of 20% SBE-β-CD in Saline (4°C,1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.
Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin 500 μL Saline)
Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO 100 μLPEG300 200 μL castor oil 650 μL Saline)
Injection Formulation 7: Ethanol : Cremophor : Saline = 10: 10 : 80 (i.e. 100 μL Ethanol 100 μL Cremophor 800 μL Saline)
Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline
Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH 900 μL Corn oil)
Injection Formulation 10: EtOH : PEG300Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH 400 μLPEG300 50 μL Tween 80 450 μL 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).
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Oral Formulation 3: Dissolved in PEG400
Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose
Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose
Oral Formulation 6: Mixing with food powders


Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.

 (Please use freshly prepared in vivo formulations for optimal results.)
Calculator

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What volume of a given 10 mM stock solution is required to make 25 ml of a 25 μM solution?
Using the equation C1V1 = C2V2, where C1=10 mM, C2=25 μM, V2=25 ml and V1 is the unknown:
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g/mol

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Note: Chemical formula is case sensitive: C12H18N3O4  c12h18n3o4
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Definitions of molecular mass, molecular weight, molar mass and molar weight:
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In vivo Formulation Calculator (Clear solution)
Step 1: Enter information below (Recommended: An additional animal to make allowance for loss during the experiment)
Step 2: Enter in vivo formulation (This is only a calculator, not the exact formulation for a specific product. Please contact us first if there is no in vivo formulation in the solubility section.)
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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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