Acetamide, 2-[3-[6-ethoxy-4-[[4-(1H-pyrazol-4-yl)phenyl]amino]-2-quinazolinyl]phenoxy]-N-(1-methylethyl)-
![Acetamide, 2-[3-[6-ethoxy-4-[[4-(1H-pyrazol-4-yl)phenyl]amino]-2-quinazolinyl]phenoxy]-N-(1-methylethyl)- Structure](CAS/20210305/GIF/1369452-53-8.gif)
- CAS No.
- 1369452-53-8
- Chemical Name:
- Acetamide, 2-[3-[6-ethoxy-4-[[4-(1H-pyrazol-4-yl)phenyl]amino]-2-quinazolinyl]phenoxy]-N-(1-methylethyl)-
- Synonyms
- KL-11743;Acetamide, 2-[3-[6-ethoxy-4-[[4-(1H-pyrazol-4-yl)phenyl]amino]-2-quinazolinyl]phenoxy]-N-(1-methylethyl)-;GLUT,inhibit,KL11743,Inhibitor,KL 11743,GLUT1,GLUT2,KL-11743,GLUT3,glucose,GLUT4,Glucose transporter,transporter
- CBNumber:
- CB99833712
- Molecular Formula:
- C30H30N6O3
- Molecular Weight:
- 522.6
- MDL Number:
- MOL File:
- 1369452-53-8.mol
Acetamide, 2-[3-[6-ethoxy-4-[[4-(1H-pyrazol-4-yl)phenyl]amino]-2-quinazolinyl]phenoxy]-N-(1-methylethyl)- Properties
| Boiling point | 739.0±60.0 °C(Predicted) |
|---|---|
| Density | 1.259±0.06 g/cm3(Predicted) |
| storage temp. | Store at -20°C |
| solubility | DMSO : 25 mg/mL (47.84 mM; ultrasonic and warming and heat to 60°C) |
| pka | 14.00±0.50(Predicted) |
| form | Solid |
| color | Light yellow to green yellow |
Acetamide, 2-[3-[6-ethoxy-4-[[4-(1H-pyrazol-4-yl)phenyl]amino]-2-quinazolinyl]phenoxy]-N-(1-methylethyl)- Chemical Properties,Uses,Production
Biological Activity
KL-11743 is a potent, orally active, and glucose-competitive inhibitor of the class I glucose transporters, with IC50s of 115, 137, 90, and 68 nM for GLUT1, GLUT2, GLUT3, and GLUT4, respectively. KL-11743 specifically blocks glucose metabolism. KL-11743 can synergize with electron transport inhibitors to induce cell death[1][2][3]. 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 IC50 of 677 nM[3].KL-11743 inhibits the growth of KEAP1-mutant lung cancer cells with more potency compared to KEAP1-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 IC50 of 127 nM[3]. 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 of KEAP1 KO 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].
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.
Acetamide, 2-[3-[6-ethoxy-4-[[4-(1H-pyrazol-4-yl)phenyl]amino]-2-quinazolinyl]phenoxy]-N-(1-methylethyl)- Preparation Products And Raw materials
Raw materials
Preparation Products
Acetamide, 2-[3-[6-ethoxy-4-[[4-(1H-pyrazol-4-yl)phenyl]amino]-2-quinazolinyl]phenoxy]-N-(1-methylethyl)- Suppliers
| Supplier | Tel | Country | ProdList | Advantage | |
|---|---|---|---|---|---|
| ATK CHEMICAL COMPANY LIMITED | +undefined-21-51877795 | ivan@atkchemical.com | China | 32760 | 60 |
| BOC Sciences | +1-631-485-4226 | inquiry@bocsci.com | United States | 19553 | 58 |
| TargetMol Chemicals Inc. | +1-781-999-5354 | support@targetmol.com | United States | 19973 | 58 |
| Aladdin Scientific | +1-+1(833)-552-7181 | sales@aladdinsci.com | United States | 52927 | 58 |
| Wuhan Jingkang en Biomedical Technology Co., Ltd | +8613720134139 | orders@jknbiochem.com | China | 4692 | 58 |
| ShangHai Biochempartner Co.,Ltd | 17754423994 17754423994 | 2853530910@QQ.com | China | 8013 | 62 |
| Shanghai Chaolan Chemical Technology Center | QQ:65489617 15618227136 | info@SuperLan-chem.com | China | 9887 | 58 |
| Shanghai SuperLan Chemcial Technique Centre | 021-2022843681 15618226720 | chaolaichem@foxmail.com | China | 8514 | 58 |
| Fujian boshi pharmaceutical technology co. LTD | 18120708884 | 393612455@qq.com | China | 255 | 58 |
| TargetMol Chemicals Inc. | 4008200310 | marketing@tsbiochem.com | China | 24017 | 58 |