Home Metabolism SCD inhibitor MK-8245

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MK-8245 SCD inhibitor

Cat.No.S1158

MK-8245 is an liver-targeting inhibitor of stearoyl-CoA desaturase (SCD) with IC50 of 1 nM for human SCD1 and 3 nM for both rat SCD1 and mouse SCD1, with anti-diabetic and anti-dyslipidemic efficacy. Phase 2.
MK-8245 SCD inhibitor Chemical Structure

Chemical Structure

Molecular Weight: 467.25

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Chemical Information, Storage & Stability

Molecular Weight 467.25 Formula

C17H16BrFN6O4

 Storage (From the date of receipt)
CAS No. 1030612-90-8 Download SDF Storage of Stock Solutions

Synonyms N/A Smiles C1CN(CCC1OC2=C(C=CC(=C2)F)Br)C3=NOC(=C3)C4=NN(N=N4)CC(=O)O

Solubility

In vitro
Batch:

DMSO : 93 mg/mL (199.03 mM)
(Moisture-contaminated DMSO may reduce solubility. Use fresh, anhydrous DMSO.)

Water : Insoluble

Ethanol : Insoluble

Molarity Calculator

Mass Concentration Volume Molecular Weight

In vivo
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Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O, mix and clarify.

Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.

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Mechanism of Action

Features
A potent hepatic SCD inhibitor, and does not affect SCD enzyme in skin and eye tissues like other systemically distributed SCD inhibitors.
Targets/IC50/Ki
SCD1 (human) [1]
1 nM
SCD1 (rat) [1]
3 nM
SCD1 (mouse) [1]
3 nM
In vitro
MK-8245, a phenoxy piperidine isoxazole derivative, has been identified as a potent and liver-specific SCD inhibitor. It contains a tetrazole acetic acid moiety, which is the key molecule for OATPs recognition and liver-targeting. This compound displays similar potencies against human, rat and mouse SCD1 with IC50 values of 1 nM for human SCD1 and 3 nM for both rat SCD1 and mouse SCD1. It exhibits a significant SCD inhibition in the rat hepatocyte assay which contains functional, active OATPs with IC50 of 68 nM, while being only weakly active in the HepG2 cell assay which is devoid of active OATPs with IC50 of ~1 μM. It displays highly selective activity for the Δ-5 and Δ-6 desaturases (i.e., >100000 μM vs rat and human Δ5D and Δ6D as assessed in the HepG assay. [1]
In vivo
Administration of MK-8245 at 10 mg/kg in mice exhibits a tissue distribution profile concentrated in the liver. It shows a liver-to-Harderian gland ratio of 21, suggesting a high degree of liver-targeting compared to a systemically distributed compound with liver-to-Harderian gland ratio of 1.5. Oral dosing of this compound in mice, rats, dogs, and rhesus monkeys demonstrates that it is distributed mainly to the liver, with low exposure in tissues associated with potential adverse events. The liver-to-skin ratios are >30:1 in all four species. Administration of this chemical to eDIO mice before the glucose challenge improves glucose clearance in a dose-dependent manner with ED50 of 7 mg/kg. [1]
References

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