| Size | Price | |
|---|---|---|
| 500mg | ||
| 1g | ||
| Other Sizes |
| ln Vitro |
PROTAC HMGCR Degrader-1 (compound 21 b) is an orally active prodrug derived from PROTAC HMGCR Degrader-2 (compound 21 c). PROTAC HMGCR Degrader-2 is an HMGCR PROTAC degrader that degrades HMGCR in a VHL-dependent manner in Insig gene-silenced HepG2 cells, with a DC50 of 120 nM [1]. PROTAC HMGCR Degrader-1 (0.01-3 μM, treated for 16 hours) tends to act as an HMGCR inhibitor rather than a degrader in HepG2 cells at high doses, with a maximum degradation rate (Dmax) of 56% at a high dose of 1 μM [1]. PROTAC HMGCR Degrader-1 (1 μM, treated for 16 hours) can prevent compensatory upregulation of HMGCR in artificial liver HepG2 cells [1].
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| ln Vivo |
PROTAC HMGCR Degrader-1 (compound 21b) (20 or 60 mg/kg, intravenous, once daily for 5 weeks) showed good efficacy in promoting the excretion of HMGCR from the MFD27 diet at low doses in a mid-fat diet-induced model, and when used in combination with good lovastatin, it also showed good safety [1].
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| Cell Assay |
Western Blot Analysis[1]
Cell Types: HepG2 cells Tested Concentrations: 0.01. 0.03, 0.1, 0.3, 1 and 3 μM Incubation Duration: 16 h Experimental Results: Attenuated the upregulation of HMGCR at low concentration. Increase in HMGCR expression at high concentration. Western Blot Analysis[1] Cell Types: HepG2 cells Tested Concentrations: 1 μM Incubation Duration: 16 h Experimental Results: Effectively attenuated the compensatory upregulation of HMGCR. |
| Animal Protocol |
Animal/Disease Models: MFD (medium-fat containing 12% fat, 0.5% so dium cholate and 1.25% cholesterol) (8 weeks) induced-male C57BL/6 mice (20e24 g)[1]
Doses: 20 or 60 mg/kg Route of Administration: p.o., once a day for 5 weeks Experimental Results: Was well tolerated, with no significant change in body weight and food intake. Demonstrated similar effects to lovastatin. Decreased total cholesterol (TC), LDL-C and triglyceride (TG) in serum of mice fed on MFD. Enhanced the reduction in serum lipid levels when combination with lovastatin. Reduced serum TC and cholesteryl esters to lower levels at a higher dose of 60 mg/kg. Reduced hepatic TC and TG in a dose-dependent manner. Ameliorated MFD-induced steatosis and lipid deposition in liver sections. Induced robust HMGCR degradation at 16 h after final gavage even at a low dose of 20 mg/kg. Was more effective in lowering total lipids (TC, cholesteryl ester and TG) when cotreated with lovastatin. |
| References |
| Molecular Formula |
C53H77N5O9S
|
|---|---|
| Molecular Weight |
960.27
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| CAS # |
2715104-45-1
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| Appearance |
Typically exists as solids at room temperature
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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) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
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|---|---|
| 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
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *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 : PEG300 ：Tween 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). View More
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)] 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). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.0414 mL | 5.2069 mL | 10.4137 mL | |
| 5 mM | 0.2083 mL | 1.0414 mL | 2.0827 mL | |
| 10 mM | 0.1041 mL | 0.5207 mL | 1.0414 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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