A922500

製品コードS2674 バッチS267403

印刷

化学情報

Chemical Structure Synonyms DGAT-1 Inhibitor 4a Storage
(From the date of receipt)		 3 years -20°C powder
1 years -80°C in solvent
化学式

C26H24N2O4
分子量 428.48 CAS No. 959122-11-3
Solubility (25°C)* 体外 DMSO 86 mg/mL (200.7 mM)
Water Insoluble
Ethanol Insoluble
体内 （毎回新しく調製した物を用意してください）
Clear solution
5%DMSO 40%PEG300 5%Tween80 50%ddH2O
4.3mg/ml Taking the 1 mL working solution as an example, add 50 μL 86 mg/ml clarified DMSO stock solution to 400 μL PEG300, mix evenly to clarify it; add 50 μL Tween80 to the above system, mix evenly to clarify it; then continue to add 500 μL ddH2O to adjust the volume to 1 mL. The mixed solution should be used immediately for optimal results. 
* <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.

溶剤液（一定の濃度）を調合する

生物活性

製品説明 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.
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]
特徴 A potent, selective, and orally bioavailable DGAT-1 inhibitor.

プロトコル(参考用のみ)

キナーゼアッセイ 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
細胞アッセイ 細胞株 Cell-free assays
濃度 9 and 22 nM
反応時間
実験の流れ
動物実験 動物モデル Thirteen-week-old male Golden Syrian hamsters with hyperlipidemia, Ten-week-old Male Zucker fatty rats
投薬量 0.03, 0.3, and 3 mg/kg
投与方法 Oral gavage

Selleckの高級品が、幾つかの出版された研究調査結果（以下を含む）で使われた：

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

長期の保管のために-20°Cの下で製品を保ってください。

人間や獣医の診断であるか治療的な使用のためにでない。

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