PROTAC HMGCR Degrader-1
PROTAC HMGCR Degrader-1 is an orally active HMGCR PROTAC degrader with IC50 of 1.32 μM. PROTAC HMGCR Degrader-1 is a lactone prodrug of PROTAC HMGCR Degrader-2 (HY-181134). PROTAC HMGCR Degrader-1 achieves high plasma exposure of the active ingredient leading to robust HMGCR degradation and demonstrating promising cholesterol-lowering efficacy in vivo. PROTAC HMGCR Degrader-1 can be used for hyperlipidemia research.
For research use only. We do not sell to patients.
- CAS No.: 2715104-45-1
- Formula: C53H77N5O9S
- Molecular Weight:960.27
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Storage:
Please store the product under the recommended conditions in the Certificate of Analysis.
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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Biological Activity
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Chemical Information
- Purity & Documentation
- References
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Biological Activity
PROTAC HMGCR Degrader-1 (compound 21 b) is a lactone prodrug of PROTAC HMGCR Degrader-2 (HY-181134) (compound 21 c). PROTAC HMGCR Degrader-2 is a HMGCR PROTAC degrader degrading HMGCR in Insig-silenced HepG2 cells with DC50 of 120 nM through a VHL-dependent manner [1].
PROTAC HMGCR Degrader-1 (0.01-3 μM, 16 h) preferentially acts as HMGCR inhibitors over degraders at high doses in HepG2 cells, achieves a maximum degradation (Dmax) of 56% at a high dose of 1 μM[1].
PROTAC HMGCR Degrader-1 (1 μM, 16 h) prevents the compensatory upregulation of HMGCR in human hepatic HepG2 cells[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:HepG2 cells
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Concentration:0.01. 0.03, 0.1, 0.3, 1 and 3 μM
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Incubation Time:16 h
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Result:Attenuated the upregulation of HMGCR at low concentration.
Increase in HMGCR expression at high concentration.
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Cell Line:HepG2 cells
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Concentration:1 μM
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Incubation Time:16 h
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Result:Effectively attenuated the compensatory upregulation of HMGCR.
| Species | Dose | Route | T1/2 | Tmax | Cmax | AUC0-24 | AUC0-∞ |
|---|---|---|---|---|---|---|---|
| Mice[1] | 60 mg/kg | p.o. | 5.1 h | 8.0 h | 0.47 μM | 5.0 μM | 5.4 μM |
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model: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]
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Dosage:20 or 60 mg/kg
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Administration:p.o., once a day for 5 weeks
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Result: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.
Chemical Information
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CAS No. 2715104-45-1
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Molecular Weight 960.27
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Formula C53H77N5O9S
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SMILES
O=C(O[C@H]1C[C@@H](C)C=C2C=C[C@H](C)[C@H](CC[C@@H]3C[C@@H](O)CC(O3)=O)[C@@]12[H])NCCCCCCCCCCC(N[C@@H](C(C)(C)C)C(N4[C@H](C(NCC5=CC=C(C6=C(C)N=CS6)C=C5)=O)C[C@@H](O)C4)=O)=O
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Shipping
Room temperature in continental US; may vary elsewhere.
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Storage
Please store the product under the recommended conditions in the Certificate of Analysis.
Purity & Documentation
References
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
PROTAC HMGCR Degrader-1 Related Classifications
HY-171823 Related Classifications
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