U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

Details

Stereochemistry ABSOLUTE
Molecular Formula C20H18F6N4O
Molecular Weight 444.3735
Optical Activity UNSPECIFIED
Defined Stereocenters 1 / 1
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of MK-5046

SMILES

O[C@@](CC1=NC=C(CC2(CC2)C(F)(F)F)N1)(C3=CC=C(C=C3)N4C=CC=N4)C(F)(F)F

InChI

InChIKey=UJINBEQCDMOAHM-SFHVURJKSA-N
InChI=1S/C20H18F6N4O/c21-19(22,23)17(6-7-17)10-14-12-27-16(29-14)11-18(31,20(24,25)26)13-2-4-15(5-3-13)30-9-1-8-28-30/h1-5,8-9,12,31H,6-7,10-11H2,(H,27,29)/t18-/m0/s1

HIDE SMILES / InChI
Molecular Formula C20H18F6N4O
Molecular Weight 444.3735
Charge 0
Count
Stereochemistry ABSOLUTE
Additional Stereochemistry No
Defined Stereocenters 1 / 1
E/Z Centers 0
Optical Activity UNSPECIFIED

Description

MK-5046 is an orally active, potent, selective agonist of the orphan G protein-coupled receptor bombesin receptor subtype-3 (BRS-3). In pharmacological testing using diet-induced obese mice, MK-5046 caused mechanism-based, dose-dependent reductions in food intake and body weight.

CNS Activity

CNS Penetrant
2554
Curator's Comment: Known to be CNS penetrant in mice. Human data not available.

Originator

Merck
216
Curator's Comment: # Merck Research Laboratories

Approval Year

Unknown
139594
Targets

Targets

Primary TargetPharmacologyConditionPotency
Agonist
2678
 3.7 nM [Ki]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Preclinical
Unknown

Approved Use

Unknown
PubMed

PubMed

TitleDatePubMed
Patents

Patents

WO 2008051404 A2
1
WO 2008051406 A2
1

Sample Use Guides

In Vivo Use Guide
In mouse model of obesity, MK-5046 (25 mg/kg/day by sc infusion) caused reductions in body weight (8-9% as compared to vehicle-dosed animals) thatwere sustained for 14 days with no evidence of tachyphylaxis.
Route of Administration: Other
In Vitro Use Guide
Receptor binding was performed using membranes from CHO or HEK293 cells overexpressing the bombesine receptor. A 30 pM concentration of [125I]-[D-Tyr6,β-Ala11,Phe13,Nle14]-bombesin(6-14) (human assay) and 660 pM [3H]Bag-3 (rat and mouse assays) were used. For functional assays, agonist induced mobilization of intracellular Ca2+ was measured HEK293AEQ cells overexpressing BRS-3, using an aequorin bioluminescence assay.
Substance Class Chemical
Created
by admin
on Sat Dec 16 18:27:40 GMT 2023
Edited
by admin
on Sat Dec 16 18:27:40 GMT 2023
Record UNII
QHZ72H8F6P
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
MK-5046
Common Name English
(2S)-1,1,1-trifluoro-2-[4-(1H-pyrazol-1-yl)phenyl]-3-(4-{[1-(trifluoromethyl)cyclopropyl]methyl}-1H-imidazol-2-yl)propan-2-ol
Systematic Name English
1H-Imidazole-2-ethanol, α-[4-(1H-pyrazol-1-yl)phenyl]-α-(trifluoromethyl)-5-[[1-(trifluoromethyl)cyclopropyl]methyl]-, (αS)-
Systematic Name English
Code System Code Type Description
PUBCHEM
49871766
Created by admin on Sat Dec 16 18:27:40 GMT 2023 , Edited by admin on Sat Dec 16 18:27:40 GMT 2023
PRIMARY
CAS
1022152-70-0
Created by admin on Sat Dec 16 18:27:40 GMT 2023 , Edited by admin on Sat Dec 16 18:27:40 GMT 2023
PRIMARY
FDA UNII
QHZ72H8F6P
Created by admin on Sat Dec 16 18:27:40 GMT 2023 , Edited by admin on Sat Dec 16 18:27:40 GMT 2023
PRIMARY
Related Record Type Details
BOMBESIN RECEPTOR SUBTYPE-3
TARGET -> AGONIST
Related Record Type Details
Structure of MK-5046
ACTIVE MOIETY
NIH
NCATS
PRIVACY ACT
ACCESSIBILITY
DISCLAIMER
HHS VULNERABILITY DISCLOSURE
For language access assistance, contact the NCATS Public Information Officer
National Center for Advancing Translational Sciences (NCATS),
6701 Democracy Boulevard, Bethesda MD 20892-4874 • 301-594-8966