KL-11743 是一种有效的，具有口服活性的葡萄糖竞争性 I 类葡萄糖转运蛋白抑制剂，抑制GLUT1，GLUT2，GLUT3和GLUT4的IC50值分别为 115 nM，137 nM，90 nM 和 68 nM。KL-11743 特异性阻断葡萄糖代谢。KL-11743 可与电子传递抑制剂协同诱导细胞死亡。
| 生物活性 | KL-11743 is a potent, orally active, and glucose-competitive inhibitor of theclass I glucose transporters, withIC50s of 115, 137, 90, and 68 nM forGLUT1,GLUT2,GLUT3, andGLUT4, respectively. KL-11743 specifically blocks glucose metabolism. KL-11743 can synergize with electron transport inhibitors to induce cell death[1][2][3]. |
| IC50& Target[3] | GLUT1 115 nM (IC50) | GLUT2 137 nM (IC50) | GLUT3 90 nM (IC50) | GLUT4 68 nM (IC50) |
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体外研究
(In Vitro) | KL-11743 (compound 8) competes with glucose for binding to GLUT1, with IC50s of 33 nM and 268 nM at 0.37 mM and 10 mM glucose, respectively[1].
KL-11743 (39-10000 nM; 24-72 h) dose-dependently inhibits the growth of HT-1080 cells, with an IC50of 677 nM[3].
KL-11743 inhibits the growth ofKEAP1-mutant lung cancer cells with more potency compared toKEAP1-WT lung cancer cells[4].
KL-11743 (0.001-10 μM) induces a rapid increase in the phosphorylation of AMPK and acetyl-coenzyme A carboxylase in HT-1080 cells[3].
KL-11743 (2 μM) inhibits glucose uptake in 786-O cells. KL-11743 increases NADP+/NADPH in NCl-H226 cells. KL-11743 induces cell death in SLC7A11-high cancer cell lines (NCl-H226 and UMRC6 cells)[2].
KL-11743 (0.001-10 μM) inhibits both glucose consumption, lactate secretion, and 2DG transport in HT-1080 fibrosarcoma cells, with IC50s of 228, 234, and 87 nM, respectively, and fully inhibited glycolytic ATP production in oligomycin-treated cells with an IC50of 127 nM[3].
Cell Viability Assay[3] | Cell Line: | HT-1080 cells | | Concentration: | 39, 78, 156, 312, 625, 1250, 2500, 5000, 10000 nM | | Incubation Time: | 24, 48, 72 hours | | Result: | Inhibited the growth of HT-1080 cells in a dose-dependent manner. |
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体内研究
(In Vivo) | KL-11743 (100 mg/kg; i.p. every two days for 5 weeks) decreases the growth of SLC7A11-high NCI-H226 xenograft tumors and was well-tolerated in vivo[2].
KL-11743 (30-100 mg/kg; a single p.o.) significantly elevates blood glucose levels and delays glucose clearance in mice challenged with 5 g/kg glucose[3].
KL-11743 significantly suppresses the growth ofKEAP1KO tumors[4].
Plasma levels of KL-11743 (100 mg/kg; i.p.) are maintained at inhibitory levels for most of the 24-hour dosing period[2].
KL-11743 (p.o) exhibits moderate oral between 30% and 15%, and favorable and dose-linear plasma exposure profile reaching concentrations of approximately 20 μM in mice (10-100 mg/kg) and rats (10-300 mg/kg)[3].
KL-11743 exhibits comparable half-lives ranging between 2.04 and 5.38 h in rats (10 mg/kg for i.v.; 10-300 mg/kg for p.o.), and 1.45-4.75 h in mice (10 mg/kg for i.v. and i.p.; 10-100 mg/kg for p.o.)[3].
| Animal Model: | 4 to 6-week-old athymic nude mice (Foxn1nu/Foxn1nu) were injected with NCI-H226 cells
100 mg/kg[2] | | Dosage: | 100 mg/kg | | Administration: | I.p. every two days for 5 weeks | | Result: | Inhibited the growth of tumors.
Exhibited extensive necrotic cell death.
Decreased PPP intermediate 6-phosphogluconate levels and increased NADP+/NADPH ratio. |
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| 运输条件 | Room temperature in continental US; may vary elsewhere. |
| 储存方式 | | Powder | -20°C | 3 years | | 4°C | 2 years | | In solvent | -80°C | 6 months | | -20°C | 1 month |
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| 溶解性数据 | In Vitro: DMSO : 25 mg/mL(47.84 mM;ultrasonic and warming and heat to 60℃) 配制储备液 | 1 mM | 1.9135 mL | 9.5675 mL | 19.1351 mL | | 5 mM | 0.3827 mL | 1.9135 mL | 3.8270 mL | | 10 mM | 0.1914 mL | 0.9568 mL | 1.9135 mL |
*请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。
储备液的保存方式和期限：-80℃, 6 months; -20℃, 1 month。-80℃ 储存时，请在 6 个月内使用，-20℃ 储存时，请在 1 个月内使用。 In Vivo: 请根据您的实验动物和给药方式选择适当的溶解方案。以下溶解方案都请先按照In Vitro方式配制澄清的储备液，再依次添加助溶剂： ——为保证实验结果的可靠性，澄清的储备液可以根据储存条件，适当保存；体内实验的工作液，建议您现用现配，当天使用；
以下溶剂前显示的百
分比是指该溶剂在您配制终溶液中的体积占比；如在配制过程中出现沉淀、析出现象，可以通过加热和/或超声的方式助溶 1. 请依序添加每种溶剂： 10% DMSO 90%corn oil Solubility: ≥ 2.08 mg/mL (3.98 mM); Clear solution
此方案可获得 ≥ 2.08 mg/mL (3.98 mM，饱和度未知) 的澄清溶液，此方案不适用于实验周期在半个月以上的实验。 以 1 mL 工作液为例，取 100 μL 20.8 mg/mL 的澄清 DMSO 储备液加到 900 μL玉米油中，混合均匀。
*以上所有助溶剂都可在本网站选购。 |
