HMG499
Based on 1 Customer Validation
HMG499 is an orally active HMGCR degrader with an EC50 of 0.39 μM. HMG499 induces HMG-CoA reductase degradation through Insig-dependent ubiquitination and proteasomal degradation pathways. HMG499, alone or in combination with Lovastatin (HY-N0504), reduces in vivo cholesterol and triglyceride levels and alleviates atherosclerotic plaques. HMG499 can be used in research related to hypercholesterolemia, hyperlipidemia, and atherosclerosis.
Para uso exclusivo en investigación. No vendemos a pacientes.
- Pureza : 96.12%
- No. CAS: 2416941-68-7
- Fòrmula: C33H54O3
- Peso molecular:498.78
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Almacenamiento:Powder -20°C, 3 years ; In solvent -80°C, 6 months , -20°C, 1 month
To place orders, for customer services and technical support, please contact: MedChemExpress USA
Tel: 609-228-6898 E-mail: [email protected] [email protected]
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Actividad biológica
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Chemical Information
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Solvente y solubilidad
- Protocolo
- Pureza y Documentación
- Referencias
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Help & FAQs
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HY-100793
SR12813HMG-CoA Reductase Inhibitor/hPXR Agonist -
HY-17504B
Rosuvastatin SodiumHMGCR Inhibitor -
HY-104051
Monacolin JCholesterol Biosynthesis Inhibitor -
HY-19671
ApomineHMGR Inhibitor -
HY-129458
CerivastatinHMG-CoA Reductase Inhibitor -
HY-100793R
SR12813 (Standard)HMG-CoA Reductase Inhibitor/hPXR Agonist -
HY-122439
Lovastatin acidHMG-CoA Inhibitor -
HY-17504BR
Rosuvastatin Sodium (Standard)Reference Standard -
HY-17504C
(3R,5R)-RosuvastatinhERG Potassium Channel Blocker/HMG-CoA Reductase Inhibitor
Actividad biológica
Descripciòn
IC50 & Target
IC50: 0.41 μM (HMG-CoA reductase)[1]
In Vitro
HMG499 does not inhibit hERG peak tail current in CHO-hERG cells, with a predicted IC50 of 1.86 mM; it does not induce the LXR target genes SREBP-1c, ABCA1, or ABCG8 in cultured cells[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
In Vivo
HMG499 (60 mg/kg/day; p.o. gavage; once daily; for 6 weeks) reduces serum and hepatic lipids in diet-induced hyperlipidemia and enhances Lovastatin-mediated lipid-lowering effects[1].
HMG499 (60 mg/kg/day; p.o. gavage; once daily; for 20 weeks) reduces atherosclerotic lesions and enhances the anti-atherosclerotic effect of Lovastatin in Western diet-fed Ldlr−/− mice[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:C57BL/6J (male, 8-week-old)[1]
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Dosage:60 mg/kg/day
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Administration:p.o. gavage; once daily; for 10 days
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Result:In chow-fed mice, HMG499 alone reduced liver HMGCR protein by 50%.
In combination with lovastatin, HMG499 reduced lovastatin-induced liver HMGCR by >13-fold relative to lovastatin alone, to approximately 2-fold of vehicle.
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Animal Model:C57BL/6J (male, 8-week-old, chow diet with10% fat, 0.2% cholesterol and 0.5% sodium cholate)[1]
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Dosage:60 mg/kg/day
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Administration:p.o. gavage; once daily; for 6 weeks
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Result:In MFMC-fed mice, HMG499 alone lowered serum and liver total cholesterol and triglyceride levels.
In combination with lovastatin, HMG499 further reduced serum and liver total cholesterol.
HMG499 alone reduced cholesterol contents in VLDL, LDL, and HDL; combination with lovastatin further lowered cholesterol in all lipoprotein fractions.
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Animal Model:Ldlr−/− (male, 8-week-old, 20% fat, 1.25% cholesterol, 0.5% sodium cholate)[1]
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Dosage:60 mg/kg/day
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Administration:p.o. gavage; once daily; for 20 weeks
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Result:In western diet-fed Ldlr−/− mice, HMG499 alone reduced serum and liver total cholesterol and triglyceride elevations.
FPLC showed that HMG499 reduced serum cholesterol in VLDL, LDL, and HDL; combination with lovastatin further decreased cholesterol in all lipoproteins, especially VLDL and LDL.
HMG499 alone reduced aortic atherosclerotic lesions compared with vehicle, and combination with lovastatin further decreased lesions.
Chemical Information
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No. CAS 2416941-68-7
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Appearance Solid
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Peso molecular 498.78
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Fòrmula C33H54O3
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Color White to off-white
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SMILES
C[C@H](CCCC(CC=C)(CC=C)O)[C@H]1CC[C@@]2([H])[C@]3([H])[C@@H](O)C=C4C(C)(C)[C@@H](O)CC[C@]4(C)[C@@]3([H])CC[C@]12C
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Envío
Room temperature in continental US; may vary elsewhere.
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Almacenamiento
Powder -20°C 3 years In solvent -80°C 6 months -20°C 1 month
Solvente y solubilidad
In Vitro:
DMSO : 200 mg/mL (400.98 mM; Need ultrasonic; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
In Vivo:
Select the appropriate dissolution method based on your experimental animal and administration route.
- For the following dissolution methods, please ensure to first prepare a clear stock solution using an In Vitro approach and then sequentially add co-solvents:
- To ensure reliable experimental results, the clarified stock solution can be appropriately stored based on storage conditions. As for the working solution for In Vivo experiments, it is recommended to prepare freshly and use it on the same day.
- The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.
In Vivo Dissolution Calculator
Please enter the basic information of animal experiments:
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Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.
Please enter your animal formula composition:
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%DMSO +
Recommended: Keep the proportion of DMSO in working solution below 2% if your animal is weak.
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%+
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+%Tween-80 + +
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%Saline +
The co-solvents required include: DMSO, . All of co-solvents are available by MedChemExpress (MCE). , Tween 80. All of co-solvents are available by MedChemExpress (MCE).
Working solution concentration: 0.22 mg/mL
Method for preparing stock solution: mg drug dissolved in μL DMSO. Stock solution concentration: mg/mL.
1. Take μL DMSO stock solution;
2. Add μL .
μL , mix evenly;
3. Then add μL Tween 80, mix evenly;
4. Then add μL
Please ensure that the stock solution in the first step is dissolved to a clear state, and add co-solvents in sequence. You can use ultrasonic heating (ultrasonic cleaner, recommended frequency 20-40 kHz), vortexing, etc. to assist dissolution.
Pureza y Documentación
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Ficha de datos (291 KB)
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SDS (251 KB)
- English - EN (251 KB)
- Français - FR (251 KB)
- Deutsch - DE (251 KB)
- Norwegian - NO (251 KB)
- Español - ES (251 KB)
- Swedish - SV (251 KB)
- Italian - IT (251 KB)
- Korean - KR (251 KB)
- Portuguese - PT (251 KB)
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Instrucciones de manejo (2659 KB)
Referencias
[1]. Jiang SY, et al. Discovery of a potent HMG-CoA reductase degrader that eliminates statin-induced reductase accumulation and lowers cholesterol. Nature communications. 2018 Dec 03;9(1):5138. [Content Brief]
[2]. Zhou Y, et al. HMG-CoA reductase degrader, SR-12813, counteracts statin-induced upregulation of HMG-CoA reductase and augments the anticancer effect of atorvastatin. Biochemical and biophysical research communications. 2023 Oct 15;677:13-19. [Content Brief]
Complete Stock Solution Preparation Table
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
| Optional Solvent | Concentration Solvent Mass | 1 mg | 5 mg | 10 mg | 25 mg |
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| DMSO | 1 mM | 2.0049 mL | 10.0245 mL | 20.0489 mL | 50.1223 mL |
| 5 mM | 0.4010 mL | 2.0049 mL | 4.0098 mL | 10.0245 mL | |
| 10 mM | 0.2005 mL | 1.0024 mL | 2.0049 mL | 5.0122 mL | |
| 15 mM | 0.1337 mL | 0.6683 mL | 1.3366 mL | 3.3415 mL | |
| 20 mM | 0.1002 mL | 0.5012 mL | 1.0024 mL | 2.5061 mL | |
| 25 mM | 0.0802 mL | 0.4010 mL | 0.8020 mL | 2.0049 mL | |
| 30 mM | 0.0668 mL | 0.3341 mL | 0.6683 mL | 1.6707 mL | |
| 40 mM | 0.0501 mL | 0.2506 mL | 0.5012 mL | 1.2531 mL | |
| 50 mM | 0.0401 mL | 0.2005 mL | 0.4010 mL | 1.0024 mL | |
| 60 mM | 0.0334 mL | 0.1671 mL | 0.3341 mL | 0.8354 mL | |
| 80 mM | 0.0251 mL | 0.1253 mL | 0.2506 mL | 0.6265 mL | |
| 100 mM | 0.0200 mL | 0.1002 mL | 0.2005 mL | 0.5012 mL |
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