| Size | Price | Stock | Qty |
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| 50mg |
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| 100mg |
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| 500mg |
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| 1g |
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| Other Sizes |
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| ln Vitro |
KL-11743 (compound 8) has IC50s of 33 nM and 268 nM at 0.37 mM and 10 mM glucose, respectively, and competes with glucose for binding to GLUT1 [1]. HT-1080 cell proliferation is dose-dependently inhibited by KL-11743 (39-10000 nM; 24-72 h), with an IC50 of 677 nM [3]. KL-11743 has a more potent inhibitory effect on the proliferation of KEAP1 mutant lung cancer cells in comparison to KEAP1-WT lung cancer cells [4]. In HT-1080 cells, KL-11743 (0.001-10 μM) causes a rapid rise in AMPK and acetyl-CoA carboxylase phosphorylation [3]. In 786-O cells, KL-11743 (2 μM) decreases the absorption of glucose. NADP+/NADPH is increased in NCl-H226 cells by KL-11743. In SLC7A11 high cancer cell lines (NCl-H226 and UMRC6 cells), KL-11743 causes cell death [2]. KL-11743 (0.001-10 μM) totally suppresses glycolytic ATP synthesis in HT-1080 fibrosarcoma cells and inhibits glucose consumption, lactate secretion, and 2DG transport with IC50 values of 228, 234, and 87 nM, respectively. 127 nM is the cellular IC50 [3].
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| ln Vivo |
KL-11743 (100 mg/kg; intraperitoneally every two days for 5 weeks) reduces the growth of SLC7A11 high NCI-H226 xenograft tumors and is well tolerated in vivo [2]. KL-11743 (30-100 mg/kg; single oral dose) significantly increases blood glucose levels and delays glucose clearance in mice challenged with 5 g/kg glucose [3]. KL-11743 significantly inhibits the growth of KEAP1 KO tumors [4]. Plasma levels of KL-11743 (100 mg/kg; i.p.) were maintained at inhibitory levels during most of the 24-hour dosing period [2]. KL-11743 (oral) exhibits moderate oral concentrations between 30% and 15% in mice (10-100 mg/kg) and rats (10-300 mg/kg), and good dose-linear plasma exposure curve, reaching a concentration of approximately 20 μM) [3]. KL-11743 exhibited comparable half-lives in rats, ranging from 2.04 to 5.38 hours (10 mg/kg intravenously; 10-300 mg/kg orally) and 1.45-4.75 hours in mice (iv and Intraperitoneal injection 10 mg/kg); 10-100 mg/kg (orally) [3].
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| Cell Assay |
Cell viability assay [3]
Cell Types: HT-1080 Cell Tested Concentrations: 39, 78, 156, 312, 625, 1250, 2500, 5000, 10000 nM Incubation Duration: 24, 48, 72 hrs (hours) Experimental Results: Inhibition of the growth of HT-1080 cells in a dose-dependent manner. |
| Animal Protocol |
Animal/Disease Models: 4 to 6 weeks old athymic nude mice (Foxn1nu/Foxn1nu) were injected with NCI-H226 cells at 100 mg/kg[2]
Doses: 100 mg/kg Route of Administration: intraperitoneal (ip) injection every two days for 5 weeks. Experimental Results: Inhibit tumor growth. Exhibits extensive necrotic cell death. The level of the PPP intermediate 6-phosphogluconate decreases and the NADP+/NADPH ratio increases. |
| References |
[1]. Liu KG, et, al. Discovery and Optimization of Glucose Uptake Inhibitors. J Med Chem. 2020 May 28;63(10):5201-5211.
[2]. Liu X, 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. [3]. Olszewski K, et, al. Inhibition of glucose transport synergizes with chemical or genetic disruption of mitochondrial metabolism and suppresses TCA cycle-deficient tumors. Cell Chem Biol. 2021 Oct 22;S2451-9456(21)00441-4. [4]. Koppula P, et, al. KEAP1 deficiency drives glucose dependency and sensitizes lung cancer cells and tumors to GLUT inhibition. iScience. 2021 May 25;24(6):102649. |
| Molecular Formula |
C30H30N6O3
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|---|---|
| Molecular Weight |
522.61
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| Exact Mass |
522.24
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| Elemental Analysis |
C, 68.95; H, 5.79; N, 16.08; O, 9.18
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| CAS # |
1369452-53-8
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| Appearance |
Solid powder
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| SMILES |
CC(C)NC(COC1=CC(C2=NC(NC3=CC=C(C4=CNN=C4)C=C3)=C(C=C(OCC)C=C5)C5=N2)=CC=C1)=O
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| InChi Key |
XKOYTLRGOQTKAU-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C30H30N6O3/c1-4-38-25-12-13-27-26(15-25)30(34-23-10-8-20(9-11-23)22-16-31-32-17-22)36-29(35-27)21-6-5-7-24(14-21)39-18-28(37)33-19(2)3/h5-17,19H,4,18H2,1-3H3,(H,31,32)(H,33,37)(H,34,35,36)
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| Chemical Name |
2-(3-(4-((4-(1H-pyrazol-4-yl)phenyl)amino)-6-ethoxyquinazolin-2-yl)phenoxy)-N-isopropylacetamide
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| Synonyms |
KL-11743; KL 11743; KL11743
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO : ~25 mg/mL (~47.84 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (3.98 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.9135 mL | 9.5674 mL | 19.1347 mL | |
| 5 mM | 0.3827 mL | 1.9135 mL | 3.8269 mL | |
| 10 mM | 0.1913 mL | 0.9567 mL | 1.9135 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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