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Details

Stereochemistry ACHIRAL
Molecular Formula C17H16BrFN6O4
Molecular Weight 467.249
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of MK-8245

SMILES

OC(=O)CN1N=NC(=N1)C2=CC(=NO2)N3CCC(CC3)OC4=CC(F)=CC=C4Br

InChI

InChIKey=UJEAABFSXKCSGI-UHFFFAOYSA-N
InChI=1S/C17H16BrFN6O4/c18-12-2-1-10(19)7-13(12)28-11-3-5-24(6-4-11)15-8-14(29-22-15)17-20-23-25(21-17)9-16(26)27/h1-2,7-8,11H,3-6,9H2,(H,26,27)

HIDE SMILES / InChI

Description

Merck was developing MK 8245, an orally active inhibitor of stearoyl CoA desaturase for the treatment of type-2 diabetes mellitus. MK-8245 is a 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. It is in Phase 2 clinical studies for type 2 diabetes mellitus.

Originator

Merck
238

Approval Year

Unknown
149,124

Targets

Primary TargetPharmacologyConditionPotency
Acyl-CoA desaturase
2
Inhibitor
8,504
 1.0 nM [IC50]

Conditions

ConditionModalityTargetsHighest PhaseProduct
Type 2 diabetes mellitus
262
 Primary
Phase II
1,147
Unknown

Cmax

ValueDoseCo-administeredAnalytePopulation
0.4 μM
10 mg/kg 2 times / day multiple, oral
 MK-8245 plasma
Mus musculus

AUC

ValueDoseCo-administeredAnalytePopulation
1 μM × h
10 mg/kg 2 times / day multiple, oral
 MK-8245 plasma
Mus musculus

T1/2

ValueDoseCo-administeredAnalytePopulation
0.7 h
10 mg/kg 2 times / day multiple, oral
 MK-8245 plasma
Mus musculus

PubMed

Patents

08063224
1
20080132542
1
20100120863
6
20120142706
1
20120149637
2
20120149683
1
20120149734
1
20120277240
1

Sample Use Guides

In Vivo Use Guide
50 mg capsules twice daily for 13 days.
Route of Administration: Oral
In Vitro Use Guide
MK-8245 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 uM.
ACTIVE MOIETY
Structure of MK-8245
NIH
NCATS
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