Dapagliflozin

製品コードS1548 バッチS154809

化学情報

	Synonyms	BMS-512148	Storage (From the date of receipt)	3 years -20°C powder (seal)
	化学式	C₂₁H₂₅ClO₆
	分子量	408.87	CAS No.	461432-26-8
Solubility (25°C)*	体外	DMSO	82 mg/mL (200.55 mM)
		Ethanol	82 mg/mL (200.55 mM)
		Water	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.

溶剤液（一定の濃度）を調合する

生物活性

製品説明	Dapagliflozin is a potent and selective hSGLT2 inhibitor with EC50 of 1.1 nM, exhibiting 1200-fold selectivity over hSGLT1. Phase 4.
in vitro	Dapagliflozin is not sensitive to hSGLT1 with a 1200-fold IC50. ^[1] Dapagliflozin is 32-fold more potent than phlorizin against hSGLT2 but 4-fold less than phlorizin against hSGLT1. Dapagliflozin is highly selective versus GLUT transporters and displays 8–9% inhibition in protein-free buffer at 20 μM and virtually no inhibition in the presence of 4% bovine serum albumin. ^[2] Dapagliflozin has good permeability across Caco-2 cell membranes and is a substrate for P-glycoprotein (P-gp) but not a significant P-gp inhibitor. Dapagliflozin is stable in rat, dog, monkey, and human serum at 10 μM. Dapagliflozin shows no inhibitory responses or induction to human P450 enzymes. The in vitro metabolic pathways Dapagliflozin are glucuronidation, hydroxylation, and O-deethylation. ^[3]
in vivo	Dapagliflozin reduces blood glucose levels by 55% after 0.1 mg/kg oral dose in hyperglycemic streptozotocin (STZ) rats, which is in part to the metabolic stability conferred by the C-glucoside linkage. Dapagliflozin displays a favorable absorption, distribution, metabolism, and excretion (ADME) profile and is orally bioavailable. ^[1] Dapagliflozin (1 mg/kg) causes significant dose-dependent glucosuria and increase in urine volume in normal rats over 24 hours post-dose. Dapagliflozin induces increase in urine glucose and urine volume excretion at 6 hours post-dose in Zucker diabetic fatty (ZDF) rats. Dapagliflozin lowers fasting and fed glucose levels in ZDF rats even by 2 weeks of treatment, without any marker of renal or liver toxicity. ^[2] Dapagliflozin significantly reduces the development of hyperglycaemia, with lowered blood glucose. Dapagliflozin could improve the insulin sensitivity, reduce β-cell mass and the development of impaired pancreatic function. ^[4]
特徴	More potent stimulator of glucosuria than other SGLT2 inhibitors.

プロトコル(参考用のみ)

キナーゼアッセイ	SGLT Binding Assays
キナーゼアッセイ	Chinese hamster ovary (CHO) cells stably expressing human SGLT2 (hSGLT2) and human SGLT1 (\hSGLT1) are utilized for the development of transport assays using the selective SGLT substrate α-methyl-D-glucopyranoside (AMG). Dapagliflozin is assayed for the ability to inhibit [¹⁴C]AMG uptake in a protein- free buffer over a 2 hours incubation period. The response curve is fitted to an empirical four-parameter model to determine the inhibitor concentration at half maximal response, reported as EC50. Protein-free buffer is used to simulate the low-protein conditions of the glomerular filtrate, which bathes the SGLT targets on the lumenal surface of the proximal tubule in the kidney.
細胞アッセイ	細胞株	NRK52E cells
	濃度	0.2 μM
	反応時間
	実験の流れ	Cells were treated with indicated concentrations of drug.
動物実験	動物モデル	Normal Sprague Dawley rats or streptozotocin induced male Sprague Dawley rats
	投薬量	0.01-10 mg/kg (1 mL/kg) followed by a 50% glucose solution (2 g/kg)
	投与方法	Dosed orally

参考

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カスタマーフィードバック

: , , Mol Cell Endocrinol, 2016, 420:37-45.

: , , Mol Cell Biochem,2015, 400(1-2):57-68.

: Data from [Data independently produced by , , Mol Metab, 2016, 5(10):1048-56.]

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：

Dapagliflozin Mitigated Elevated Disomic and Diploid Sperm in a Mouse Model of Diabetes and Recover the Disrupted Ogg1, Parp1, and P53 Gene Expression [ Biomedicines, 2023, 10.3390/biomedicines11112980]	PubMed: 38001980
Impacts of the DPP-4 Inhibitor Saxagliptin and SGLT-2 Inhibitor Dapagliflozin on the Gonads of Diabetic Mice [ Biomedicines, 2023, 11(10)2674]	PubMed: 37893048
Impacts of the DPP-4 Inhibitor Saxagliptin and SGLT-2 Inhibitor Dapagliflozin on the Gonads of Diabetic Mice [ Biomedicines, 2023, 11(10)2674]	PubMed: 37893048
Streptozotocin induces renal proximal tubular injury through p53 signaling activation [ Sci Rep, 2023, 13(1):8705]	PubMed: 37248327
Direct cardio-protection of Dapagliflozin against obesity-related cardiomyopathy via NHE1/MAPK signaling [ Acta Pharmacol Sin, 2022, 10.1038/s41401-022-00885-8]	PubMed: 35217813
Dapagliflozin Prevents High-Glucose-Induced Cellular Senescence in Renal Tubular Epithelial Cells [ Int J Mol Sci, 2022, 23(24)16107]	PubMed: 36555751
Canagliflozin promotes osteoblastic MC3T3-E1 differentiation via AMPK/RUNX2 and improves bone microarchitecture in type 2 diabetic mice [ Front Endocrinol (Lausanne), 2022, 13:1081039]	PubMed: 36589840
Dapagliflozin attenuates cholesterol overloading-induced injury in mice hepatocytes with type 2 diabetes mellitus (T2DM) via eliminating oxidative damages [ Cell Cycle, 2022, 1-14]	PubMed: 35100086
Direct actions of dapagliflozin and interactions with LCZ696 and spironolactone on cardiac fibroblasts of patients with heart failure and reduced ejection fraction [ ESC Heart Fail, 2022, 10.1002/ehf2.14186]	PubMed: 36303443
SGLT2 inhibitors therapy protects glucotoxicity-induced β-cell failure in a mouse model of human KATP-induced diabetes through mitigation of oxidative and ER stress [ PLoS One, 2022, 17(2):e0258054]	PubMed: 35180212

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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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