KL-11743是一种高效的葡萄糖竞争性I类葡萄糖转运蛋白抑制剂，KL-11743通过抑制GLUT1（IC50=115nM）、GLUT2（IC50=137nM）、GLUT3（IC50=90nM）和GLUT4（IC50=68nM）来阻断葡萄糖代谢。
Cas No.:1369452-53-8
Sample solution is provided at 25 µL, 10mM.
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KL-11743 is a potent glucose-competitive class I glucose transporter inhibitor. KL-11743 blocks glucose metabolism by inhibiting GLUT1 (IC50=115nM), GLUT2 (IC50=137nM), GLUT3 (IC50=90nM), and GLUT4 (IC50=68nM)[1-2]. KL-11743 can be used in research related to SLC7A11-high tumors and KEAP1-mutant lung cancer, as well as in combination therapy with lysosomal inhibitors for refractory lung cancer[3-4].
In vitro, leukemia cell lines, patient-derived iPSC models, and primary AML patient samples were treated with KL-11743 (500nM) for 24 hours. KL-11743 effectively inhibited glucose uptake and glycolysis while significantly increasing mitochondrial respiration, particularly by enhancing Complex I function[5]. HT22 cells were treated with KL-11743 (500nM) for 2 hours. KL-11743 significantly inhibited cell viability and suppressed the high glucose-induced increase in the glucose transporter GLUT3 expression, but did not significantly inhibit the upregulation of PIEZO1[6].
In vivo, fasted C57BL/6 mice received a single oral dose of KL-11743 (30 or 100mg/kg). KL-11743 significantly increased blood glucose levels and delayed glucose clearance; Nude mice bearing patient-derived xenograft models (with SDHA-D38V mutation) were treated orally with KL-11743 (100mg/kg) daily. KL-11743 inhibited tumor growth[7]. Mice bearing SLC7A11-high tumors (such as NCI-H226 xenografts or patient-derived xenografts) were administered KL-11743 (100mg/kg) via intraperitoneal injection every other day for 5 weeks. KL-11743 significantly suppressed the growth of SLC7A11-high tumors, selectively increased the NADP+/NADPH ratio specifically in these tumors, and caused no significant pathological changes or body weight loss[8].
References:
[1] Liu KG, Kim JI, Olszewski K, et al. Discovery and Optimization of Glucose Uptake Inhibitors. J Med Chem. 2020 May 28;63(10):5201-5211.
[2] Koppula P, Olszewski K, Zhang Y, et al. KEAP1 deficiency drives glucose dependency and sensitizes lung cancer cells and tumors to GLUT inhibition. iScience. 2021 May 25;24(6):102649.
[3] Chen W, Lin C, Gao Z, et al. A tumor microenvironment-responsive nanocomposite for enhanced copper retention and hypoxia reversal to promote cuproptosis in tumor treatment. Acta Biomater. 2025 Aug;202:463-475.
[4] Wang X, Li J, Luo Z, et al. ATP-Exhausted Strategy Induced Anti-Tumor Low-Temperature Photothermal Therapy Based on Rare Earth Nanocrystals Modified Hollow Porous MnO Nanozyme with TME-Activated NIR-II Imaging. Small. 2025 Apr;21(14):e2410070.
[5] Komza M, Khatun J, Gelles JD, et al. Metabolic adaptations to acute glucose uptake inhibition converge upon mitochondrial respiration for leukemia cell survival. Cell Commun Signal. 2025 Jan 25;23(1):47.
[6] Liu H, Zhou L, Wang X, et al. PIEZO1 as a new target for hyperglycemic stress-induced neuropathic injury: The potential therapeutic role of bezafibrate. Biomed Pharmacother. 2024 Jul;176:116837.
[7] Olszewski K, Barsotti A, Feng XJ, et al. Inhibition of glucose transport synergizes with chemical or genetic disruption of mitochondrial metabolism and suppresses TCA cycle-deficient tumors. Cell Chem Biol. 2022 Mar 17;29(3):423-435.e10.
[8] Liu X, Olszewski K, Zhang Y, et al. Cystine transporter regulation of pentose phosphate pathway dependency and disulfide stress exposes a targetable metabolic vulnerability in cancer. Nat Cell Biol. 2020 Apr;22(4):476-486.
KL-11743是一种高效的葡萄糖竞争性I类葡萄糖转运蛋白抑制剂，KL-11743通过抑制GLUT1（IC50=115nM）、GLUT2（IC50=137nM）、GLUT3（IC50=90nM）和GLUT4（IC50=68nM）来阻断葡萄糖代谢[1-2]。KL-11743可用于SLC7A11高表达肿瘤和KEAP1突变型肺癌的相关研究，以及与溶酶体抑制剂联合治疗难治性肺癌[3-4]。
在体外，KL-11743（500nM）处理白血病细胞系、患者来源的iPSC模型及原代AML患者样本24小时。KL-11743可有效抑制葡萄糖摄取和糖酵解，同时显著增加了线粒体呼吸，特别是增强了complex I的功能[5]。KL-11743（500nM）处理HT22细胞2小时。KL-11743显著抑制细胞活力，抑制高糖诱导的葡萄糖转运蛋白GLUT3表达增加，但不会显著抑制PIEZO1的上调[6]。
在体内，KL-11743（30或100mg/kg）单次口服用于处理禁食的C57BL/6小鼠。KL-11743显著升高了血糖水平并延迟了葡萄糖清除；KL-11743（100mg/kg）每天口服用于处理携带患者来源异种移植模型（SDHA-D38V突变）的裸鼠。KL-11743抑制了肿瘤的生长[7]。KL-11743（100mg/kg）每两日一次腹腔注射，用于处理携带SLC7A11高表达肿瘤（如NCI-H226异种移植瘤或患者来源异种移植瘤）的小鼠5周。KL-11743显著抑制了SLC7A11高表达肿瘤的生长，并选择性增加了此类肿瘤中的NADP+/NADPH比值，且未引起明显的病理变化或体重减轻[8]。
| Cell experiment [1]: | |
Cell lines | HT22 cells (mouse hippocampal neuronal cell line) |
Preparation Method | HT22 cells were maintained in high-glucose DMEM supplemented with 10% fetal bovine serum (FBS) and 1% penicillin-streptomycin at 37°C, 5% CO₂. Cells were treated with KL-11743 (500nM) for 2 hours, then incubated with glucose for 24h. |
Reaction Conditions | 500nM; 2 hours pretreatment. |
Applications | KL11743 significantly inhibited HT22 cell viability. KL11743 pretreatment did not significantly inhibit the upregulation of PIEZO1 induced by high glucose (Glu), but treatment with KL11743 alone significantly upregulated PIEZO1 compared to the control group. KL11743 also enhanced the expression of glucose transporter GLUT3. |
| Animal experiment [2]: | |
Animal models | Athymic nude mice (Foxn1nu/Foxn1nu) for cell line xenografts; NOD scid gamma (NSG) mice for patient-derived xenografts (PDXs) |
Preparation Method | KL-11743 was administered via intraperitoneal injection (i.p.) at a dose of 100mg/kg every two days for 5 weeks. |
Dosage form | 100mg/kg; i.p.; every two days for 5 weeks. |
Applications | KL-11743 treatment significantly suppressed the growth of SLC7A11-high xenograft tumors and patient-derived xenografts (PDXs), but had no effect on the growth of SLC7A11-low tumors. In SLC7A11-high tumors, KL-11743 treatment induced extensive necrotic cell death, decreased levels of the pentose phosphate pathway (PPP) intermediate 6-phosphogluconate, and specifically increased the NADP+/NADPH ratio. KL-11743 was well-tolerated in vivo, with no significant pathological changes in major organs or weight loss observed. |
References: | |
| Cas No. | 1369452-53-8 | SDF | Download SDF |
| 分子式 | C30H30N6O3 | 分子量 | 522.6 |
| 溶解度 | DMSO : 25 mg/mL (47.84 mM; ultrasonic and warming and heat to 60°C) | 储存条件 | Store at -20°C |
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| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 1.9135 mL | 9.5675 mL | 19.1351 mL |
| 5 mM | 382.7 μL | 1.9135 mL | 3.827 mL |
| 10 mM | 191.4 μL | 956.8 μL | 1.9135 mL |
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| % DMSO % % Tween 80 % saline | ||||||||||
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2.
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