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Dapagliflozin

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Chemical Structure| 461432-26-8 同义名 : 达格列嗪 ;BMS-512148
CAS号 : 461432-26-8
货号 : A120381
分子式 : C21H25ClO6
纯度 : 97%
分子量 : 408.87
MDL号 : MFCD13182359
存储条件：

粉末 Sealed in dry,2-8°C

液体 -20°C:3-6个月-80°C:12个月
溶解度 :

DMSO: 105 mg/mL(256.81 mM)，注意：DMSO长时间开封后，会吸水并导致溶解能力下降，请避免使用长期开封的DMSO

H2O: 50 mg/mL(122.29 mM)，配合低频超声助溶
动物实验配方：

IP 2% DMSO+2% Tween80+40% PEG300+water 2.4 mg/mL clear

PO 0.5% CMC-Na 16 mg/mL suspension

生物活性
靶点

  • SGLT2

    hSGLT2, EC50:1.1 nM
描述 The sodium-dependent glucose transport (SGLT) proteins belong to the sodium glucose cotransporter family. Sodium-dependent glucose transport 2 (SGLT2) is a high-capacity, low-affinity transporter that is expressed mainly in the kidney. It has a Na(+) to glucose coupling ratio of 1:1. It is estimated that 90% of renal glucose reabsorption is facilitated by SGLT2 residing on the surface of the epithelial cells lining the S1 segment of the proximal tubule. Dapagliflozin is a potent and selective SGLT2 inhibitor. In an experiment system of Chinese hamster ovary cells stably expressing human SGLT2 and SGLT1, data yielded by monitoring inhibition of AMG showed that the EC50 of dapagliflozin for human SGLT2 inhibition was 1.1 nM, while that for human SGLT1 was 1390 nM[7]. In acute normal and diabetic rat studies, SD or ZDF rats were dosed orally with single doses of dapagliflozin at 0.01 mg/kg, 0.1 mg.kg, 1 mg/kg or 10 mg/kg. In normal rats， the results were that dapagliflozin caused significant dose-dependent glucosuria and increase in urine volume, with 1 mg/kg producing a 400-fold increase in urine glucose and a threefold increase in urine volume versus vehicle over 24 h post-dose. Dapagliflozin administration was also associated with a reduction in glucose area under the curve over 1 h post-dose at 1 and 10 mg/kg doses in the glucose tolerance test in normal rats. In ZDF rats, dapagliflozin dose-dependently increased urine glucose and urine volume excretion at 6 h post-dose [8]. In another study, dapagliflozin was administrated at the dose of 0.5 mg/kg orally once daily for 15 days. When measured 24 h after the final dose on day 15, ZDF rats treated with dapagliflozin displayed a 53% decrease in 18-h FPG level compared with vehicle-treated rats[8].
细胞研究
细胞系 浓度 检测类型 检测时间 活动说明 数据源
CHO cells Function assay 2 h Inhibition of human SGLT2 expressed in CHO cells assessed as [14C]alpha-methyl-D-glucopyranoside uptake after 2 hrs by liquid scintillation counting, IC50=0.00049 μM 20434909
CHOK1 cells Function assay 3 h Inhibition of human SGLT2 expressed in CHOK1 cells assessed as inhibition of [14C]-AMG uptake after 3 hrs by microbeta scintillation counting analysis, IC50=0.001 μM 24842618
COS-7 cells Function assay 2 h Inhibition of human SGLT1 transfected in COS-7 cells assessed as AMG uptake after 2 hrs by scintillation counting, IC50=0.89 μM 19896374
临床研究
NCT号 适应症或疾病 临床期 招募状态 预计完成时间 地点
NCT02096705 Diabetes Phase 3 Completed - -
NCT03565458 Type 2 Diabetes Mellitus Phase 1 Active, not recruiting December 22, 2018 Korea, Republic of ... 展开 >> LG chem Seoul, Gangseo-Gu, Korea, Republic of, 07795 收起 <<
NCT02096705 - Completed - -
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

2.45mL

0.49mL

0.24mL

12.23mL

2.45mL

1.22mL

24.46mL

4.89mL

2.45mL
参考文献

[1]Han S, Hagan DL, et al. Dapagliflozin, a selective SGLT2 inhibitor, improves glucose homeostasis in normal and diabetic rats. Diabetes. 2008 Jun;57(6):1723-9.

[2]Perry RJ, Rabin-Court A, et al. Dehydration and insulinopenia are necessary and sufficient for euglycemic ketoacidosis in SGLT2 inhibitor-treated rats. Nat Commun. 2019 Feb 1;10(1):548.

[3]Erdogan MA, Yusuf D, et al. Highly selective SGLT2 inhibitor dapagliflozin reduces seizure activity in pentylenetetrazol-induced murine model of epilepsy. BMC Neurol. 2018 Jun 7;18(1):81.

[4]Meng W, Ellsworth BA, et al. Discovery of dapagliflozin: a potent, selective renal sodium-dependent glucose cotransporter 2 (SGLT2) inhibitor for the treatment of type 2 diabetes. J Med Chem. 2008 Mar 13;51(5):1145-9.

[5]Meng W, Ellsworth BA, Nirschl AA, McCann PJ, Patel M, Girotra RN, Wu G, Sher PM, Morrison EP, Biller SA, Zahler R, Deshpande PP, Pullockaran A, Hagan DL, Morgan N, Taylor JR, Obermeier MT, Humphreys WG, Khanna A, Discenza L, Robertson JG, Wang A, Han S, Wetterau JR, Janovitz EB, Flint OP, Whaley JM, Washburn WN. Discovery of dapagliflozin: a potent, selective renal sodium-dependent glucose cotransporter 2 (SGLT2) inhibitor for the treatment of type 2 diabetes. J Med Chem. 2008 Mar 13;51(5):1145-9. doi: 10.1021/jm701272q. Epub 2008 Feb 9. PMID: 18260618.

[6]Han S, Hagan DL, Taylor JR, Xin L, Meng W, Biller SA, Wetterau JR, Washburn WN, Whaley JM. Dapagliflozin, a selective SGLT2 inhibitor, improves glucose homeostasis in normal and diabetic rats. Diabetes. 2008 Jun;57(6):1723-9. doi: 10.2337/db07-1472. Epub 2008 Mar 20. PMID: 18356408.