| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| Targets |
HSL-IN-2 targets hormone-sensitive lipase (HSL), a key enzyme in lipid metabolism that catalyzes the hydrolysis of triglycerides stored in adipose tissue. HSL is responsible for the rate-limiting step in lipolysis, the breakdown of stored triglycerides into free fatty acids and glycerol. The compound is a selective inhibitor of HSL with an IC50 of 0.023 microM, indicating potent inhibitory activity. By inhibiting HSL, HSL-IN-2 reduces the release of free fatty acids from adipose tissue, which can have beneficial effects on metabolic parameters including insulin sensitivity and lipid profiles. The selectivity of HSL-IN-2 for HSL over other lipases is an important feature of its pharmacological profile.
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| ln Vitro |
BAY 59-9435 greatly lowers the culture medium's elevated IL-6 induced by isoproterenol. BAY 59-9435 inhibits the expression of SphK1 produced by isoproterenol [3].
In vitro enzyme assays have demonstrated that HSL-IN-2 is a potent and selective inhibitor of hormone-sensitive lipase with an IC50 of 0.023 microM. The compound shows high specificity for HSL, making it a valuable tool for studying the role of this enzyme in lipid metabolism. The in vitro activity of HSL-IN-2 has been characterized using purified HSL enzyme preparations in standard lipase activity assays. The compound's potency against HSL is in the nanomolar range, indicating strong enzyme inhibition. Detailed structure-activity relationship studies have been conducted to optimize the inhibitory activity of this compound class. These studies support the use of HSL-IN-2 as a pharmacological tool for investigating HSL biology. |
| ln Vivo |
In vivo studies on HSL-IN-2 are limited. As a selective HSL inhibitor, the compound has potential applications in the treatment of metabolic disorders such as obesity, insulin resistance, and dyslipidemia. By inhibiting HSL and reducing the release of free fatty acids from adipose tissue, HSL-IN-2 could improve insulin sensitivity and reduce lipid accumulation in non-adipose tissues. However, specific in vivo efficacy data for HSL-IN-2 are not widely available in the published literature. Animal studies would be needed to evaluate the compound's effects on body weight, glucose metabolism, and lipid parameters.
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| Enzyme Assay |
The in vitro enzyme assay for HSL-IN-2 typically involves measuring the inhibition of hormone-sensitive lipase activity using purified HSL enzyme and a suitable substrate. The assay is performed in a buffer system optimized for HSL activity, with the compound added at varying concentrations to determine the IC50 value. The reaction is initiated by the addition of substrate and terminated after a specified incubation period. The amount of hydrolyzed product (free fatty acids) is quantified using a colorimetric or fluorometric detection method. IC50 values are calculated by fitting the inhibition data to a sigmoidal dose-response curve. Positive and negative controls are included to validate the assay.
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| Cell Assay |
Western Blot analysis[3]
Cell Types: 3T3-L1 cells. Tested Concentrations: 10μM. Incubation Duration: 1 hour. Experimental Results: BAY pretreatment completely abolished the induction of SphK1 expression by CL. Cellular assays for HSL-IN-2 can be conducted using adipocyte cell lines such as 3T3-L1 differentiated adipocytes. Cells are treated with varying concentrations of HSL-IN-2, and lipolysis is stimulated using beta-adrenergic agonists such as isoproterenol or forskolin. The amount of glycerol or free fatty acids released into the culture medium is measured as an indicator of lipolytic activity. The compound's inhibitory effect on HSL is demonstrated by a reduction in stimulated lipolysis. Cell viability assays are performed to ensure that any observed effects are not due to cytotoxicity. These cell-based assays confirm the compound's activity in a physiological cellular context. |
| Animal Protocol |
In vivo animal studies for HSL-IN-2 would typically involve the use of mouse or rat models of metabolic disease, such as diet-induced obesity models or genetic models of insulin resistance. The compound would be administered orally or intraperitoneally at various doses, and metabolic parameters including body weight, food intake, glucose tolerance, insulin sensitivity, and lipid profiles would be monitored. Tissue samples would be collected for analysis of triglyceride content and histopathology. However, specific in vivo protocols for HSL-IN-2 have not been published, and the compound's efficacy in animal models remains to be demonstrated.
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| ADME/Pharmacokinetics |
Pharmacokinetic data for HSL-IN-2 are limited. The compound has a molecular weight of 266.34 and a molecular formula of C14H22N2O3. For in vivo formulation, HSL-IN-2 is soluble in DMSO at 250 mg/mL and can be formulated in 10% DMSO + 40% PEG300 + 5% Tween-80 + 45% saline at 5 mg/mL. The compound should be stored as powder at -20degC for up to 3 years or in solvent at -80degC for up to 1 year. Detailed pharmacokinetic parameters such as oral bioavailability, half-life, clearance, and tissue distribution have not been determined for this compound.
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| Toxicity/Toxicokinetics |
Toxicological data for HSL-IN-2 are not available in the published literature. As a research compound, HSL-IN-2 has not been systematically evaluated for toxicity in preclinical studies. Standard toxicological assessments, including acute toxicity, repeat-dose toxicity, and genotoxicity studies, would be needed to establish the safety profile of this compound for any potential therapeutic applications. The compound's selectivity for HSL suggests that it may have a favorable safety profile, but this remains to be confirmed through appropriate toxicological studies.
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| References |
[1]. Ebdrup S, et al. Synthesis and structure-activity relationship for a novel class of potent and selective carbamoyl-triazole based inhibitors of hormone sensitive lipase. J Med Chem. 2004 Jan 15;47(2):400-10.
[2]. Elizabeth A Rondini, et al. Novel Pharmacological Probes Reveal ABHD5 as a Locus of Lipolysis Control in White and Brown AdipocytesJ Pharmacol Exp Ther. 2017 Dec;363(3):367-376. [3]. Wenliang Zhang, et al. Adipocyte lipolysis-stimulated interleukin-6 production requires sphingosine kinase 1 activity. J Biol Chem. 2014 Nov 14;289(46):32178-85. |
| Additional Infomation |
HSL-IN-2 (BAY 59-9435) is a research compound used primarily as a pharmacological tool for studying hormone-sensitive lipase biology and lipid metabolism. The compound is a potent and selective inhibitor of HSL with an IC50 of 0.023 microM. It has potential applications in the study of metabolic disorders including obesity, insulin resistance, and dyslipidemia. The compound is not approved for clinical use and is available only for research purposes. HSL-IN-2 is valuable for investigating the role of HSL in energy homeostasis and for validating HSL as a therapeutic target for metabolic diseases.
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| Molecular Formula |
C14H22N2O3
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| Molecular Weight |
266.336083889008
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| Exact Mass |
266.163
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| CAS # |
654059-21-9
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| PubChem CID |
10038557
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| Appearance |
White to off-white solid powder
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| Density |
1.1±0.1 g/cm3
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| Boiling Point |
345.8±25.0 °C at 760 mmHg
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| Flash Point |
162.9±23.2 °C
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| Vapour Pressure |
0.0±0.8 mmHg at 25°C
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| Index of Refraction |
1.522
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| LogP |
2.42
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| Hydrogen Bond Donor Count |
0
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| Hydrogen Bond Acceptor Count |
3
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| Rotatable Bond Count |
1
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| Heavy Atom Count |
19
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| Complexity |
428
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| Defined Atom Stereocenter Count |
1
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| SMILES |
O=C1C(C(C)C)=C(C)N(C(N2C[C@@H](C)CCC2)=O)O1
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| InChi Key |
XWESKOHENXWEAX-JTQLQIEISA-N
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| InChi Code |
InChI=1S/C14H22N2O3/c1-9(2)12-11(4)16(19-13(12)17)14(18)15-7-5-6-10(3)8-15/h9-10H,5-8H2,1-4H3/t10-/m0/s1
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| Chemical Name |
3-methyl-2-[(3S)-3-methylpiperidine-1-carbonyl]-4-propan-2-yl-1,2-oxazol-5-one
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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 : ~250 mg/mL (~938.65 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (7.81 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 (7.81 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in 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 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. 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. View More
Solubility in Formulation 3: ≥ 2.08 mg/mL (7.81 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 3.7546 mL | 18.7730 mL | 37.5460 mL | |
| 5 mM | 0.7509 mL | 3.7546 mL | 7.5092 mL | |
| 10 mM | 0.3755 mL | 1.8773 mL | 3.7546 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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