A922500

Catalog No.S2674 Batch:S267406

Technical Data

Formula	C₂₆H₂₄N₂O₄
Molecular Weight	428.48	CAS No.	959122-11-3
Solubility (25°C)*	In vitro	DMSO	86 mg/mL (200.7 mM)
		Water	Insoluble
		Ethanol	Insoluble
* <1 mg/ml means slightly soluble or insoluble. * Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations. * Room temperature shipping (Stability testing shows this product can be shipped without any cooling measures.)

Preparing Stock Solutions

Biological Activity

Description

A922500 (DGAT-1 Inhibitor 4a) is an inhibitor for human and mouse DGAT-1 with IC50 of 7 nM and 24 nM, respectively, good selectivity over related acyltransferases, hERG, and a panel of anti-targets.

Targets

human DGAT1 ^[1]	mouse DGAT1 ^[1]
7 nM	24 nM

In vitro

A 922500 inhibits the phylogenetic family members acyl coenzyme A cholesterol acyltransferase-1 and -2 with IC50 of 296 μM. ^[1]

A 922500 potently inhibits huDGAT-1 and mseDGAT-1. ^[2]

In vivo

Zucker fatty rats and diet-induced dyslipidemic hamsters are dosed orally with A 922500 (0.03, 0.3, and 3 mg/kg) for 14 days. Serum triglycerides ae significantly reduced by the 3 mg/kg dose of A 922500 in both the Zucker fatty rat (39%) and hyperlipidemic hamster (53%). These serum triglyceride changes are accompanied by significant reductions in free fatty acid levels by 32% in the Zucker fatty rat and 55% in the hyperlipidemic hamster. In addition, high-density lipoprotein-cholesterol is significantly increases (25%) in the Zucker fatty rat by A 922500 administered at 3 mg/kg. ^[1]

A 922500 confers weight loss and a reduction in liver triglycerides when dosed chronically in DIO mice and depletes serum triglycerides following a lipid challenge in a dose-dependent manner, thus, reproducing major phenotypical characteristics of DGAT-1(-/-) mice. ^[2]

A 922500 (0.03, 0.3 and 3 mg/kg, p.o.) dose-dependently attenuates the maximal postprandial rise in serum triglyceride concentrations. ^[3]

Features

A potent, selective, and orally bioavailable DGAT-1 inhibitor.

Protocol (from reference)

Kinase Assay:^{^[2]}	In vitro DGAT-1 activity inhibition assay DGAT-1 activity is determined as follows: Assay buffer [20 mM HEPES (pH 7.5), 2 mM MgCl₂, 0.04% BSA] containing 50 μM of enzyme substrate (didecanoyl glycerol) and 7.5 μM radiolabeled acyl-CoA substrate. [1- ¹⁴ C]decanoyl-CoA) is added to each well of a phospholipid FlashPlate. A small aliquot of membrane (1 μg/well) is added to start the reaction, which is allowed to proceed for 60 minutes. The reaction is terminated upon the addition of an equal volume (100 μL) of isopropanol. The plates are sealed, incubated overnight and counted the next morning on a TopCount Scintillation Plate Reader. DGAT-1 catalyzes the transfer of the radiolabel-led decanoyl group onto the sn-3 position of didecanoyl glycerol. The resultant radiolabeled tridecanoyl glycerol (tricaprin) preferentially binds to the hydrophobic coating on the phospholipid FlashPlate. The proximity of the S15 radiolabeled product to the solid scintillant incorporated into the bottom of the FlashPlate induces fluor release from the scintillant, which is measured in the TopCount Plate Reader. Various concentrations (e.g. 0.0001 μM, 0.001 μM, 0.01 μM, 0.1 μM, 1.0 μM, 10.0 μM) of A 922500 are added to individual wells prior to the addition of membranes. The potency of DGAT-1 inhibition for the A 922500 is determined by calculating the IC50 values defined as the inhibitor concentration from the sigmoidal dose response curve at which the enzyme activity is inhi
Animal Study:^{^[1]}	Animal Models Thirteen-week-old male Golden Syrian hamsters with hyperlipidemia, Ten-week-old Male Zucker fatty rats Dosages 0.03, 0.3, and 3 mg/kg Administration Oral gavage

Kinase Assay:^{^[2]}

In vitro DGAT-1 activity inhibition assay
DGAT-1 activity is determined as follows: Assay buffer [20 mM HEPES (pH 7.5), 2 mM MgCl₂, 0.04% BSA] containing 50 μM of enzyme substrate (didecanoyl glycerol) and 7.5 μM radiolabeled acyl-CoA substrate. [1- ¹⁴ C]decanoyl-CoA) is added to each well of a phospholipid FlashPlate. A small aliquot of membrane (1 μg/well) is added to start the reaction, which is allowed to proceed for 60 minutes. The reaction is terminated upon the addition of an equal volume (100 μL) of isopropanol. The plates are sealed, incubated overnight and counted the next morning on a TopCount Scintillation Plate Reader. DGAT-1 catalyzes the transfer of the radiolabel-led decanoyl group onto the sn-3 position of didecanoyl glycerol. The resultant radiolabeled tridecanoyl glycerol (tricaprin) preferentially binds to the hydrophobic coating on the phospholipid FlashPlate. The proximity of the S15 radiolabeled product to the solid scintillant incorporated into the bottom of the FlashPlate induces fluor release from the scintillant, which is measured in the TopCount Plate Reader. Various concentrations (e.g. 0.0001 μM, 0.001 μM, 0.01 μM, 0.1 μM, 1.0 μM, 10.0 μM) of A 922500 are added to individual wells prior to the addition of membranes. The potency of DGAT-1 inhibition for the A 922500 is determined by calculating the IC50 values defined as the inhibitor concentration from the sigmoidal dose response curve at which the enzyme activity is inhi

Animal Study:^{^[1]}

Animal Models
Thirteen-week-old male Golden Syrian hamsters with hyperlipidemia, Ten-week-old Male Zucker fatty rats
Dosages
0.03, 0.3, and 3 mg/kg
Administration
Oral gavage

References

Selleck's A922500 has been cited by 5 publications

Identification of an alternative triglyceride biosynthesis pathway [ Nature, 2023, 621(7977):171-178]	PubMed: 37648867
EGFR-phosphorylated GDH1 harmonizes with RSK2 to drive CREB activation and tumor metastasis in EGFR-activated lung cancer [ Cell Rep, 2022, 41(11):111827]	PubMed: 36516759
Metabolic inhibitor screening identifies dihydrofolate reductase as an inducer of the tumor immune escape mediator CD24 [ Immunomedicine, 2022, 2(2)e1041]	PubMed: 36816458
Up-regulation of DGAT1 in cancer tissues and tumor-infiltrating macrophages influenced survival of patients with gastric cancer [ BMC Cancer, 2021, 21(1):252]	PubMed: 33750350
DGAT1 inhibits retinol-dependent regulatory T cell formation and mediates autoimmune encephalomyelitis. [ Proc Natl Acad Sci U S A, 2019, 116(8):3126-3135]	PubMed: 30718413

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SHIPPING AND STORAGE
Selleck products are transported at room temperature. If you receive the product at room temperature, please rest assured, the Selleck Quality Inspection Department has conducted experiments to verify that the normal temperature placement of one month will not affect the biological activity of powder products. After collecting, please store the product according to the requirements described in the datasheet. Most Selleck products are stable under the recommended conditions.

NOT FOR HUMAN, VETERINARY DIAGNOSTIC OR THERAPEUTIC USE.