[CAS NO. 1369452-53-8] KL-11743
PRODUCTS SPECIFICATIONS [1369452-53-8]
DESCRIPTION [1369452-53-8]
Overview
| MDL | - |
|---|---|
| Molecular Weight | 522.60 |
| Molecular Formula | C30H30N6O3 |
| SMILES | O=C(COC1=CC=CC(C2=NC(NC3=CC=C(C4=CNN=C4)C=C3)=C5C=C(OCC)C=CC5=N2)=C1)NC(C)C |
Summary
KL-11743 is a potent, orally active, and glucose-competitive inhibitor of the class I glucose transporters , with IC 50 s 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] .
IC50 & Target
|
GLUT1 115 nM (IC 50 ) |
GLUT2 137 nM (IC 50 ) |
GLUT3 90 nM (IC 50 ) |
GLUT4 68 nM (IC 50 ) |
In Vitro
KL-11743 (compound 8) competes with glucose for binding to GLUT1, with IC
50
s 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 IC
50
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 IC
50
s of 228, 234, and 87 nM, respectively, and fully inhibited glycolytic ATP production in oligomycin-treated cells with an IC
50
of 127 nM
[3]
.
MCE has not independently confirmed the accuracy of these methods. They are for reference only.
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. |
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 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]
.
MCE has not independently confirmed the accuracy of these methods. They are for reference only.
| 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. |
Appearance
Solid
Shipping
Room temperature in continental US; may vary elsewhere.
Storage
| Powder | -20°C | 3 years |
|---|---|---|
| 4°C | 2 years | |
| In solvent | -80°C | 6 months |
| -20°C | 1 month |
Solvent & Solubility
DMSO : 25 mg/mL ( 47.84 mM ; ultrasonic and warming and heat to 60°C)
Stock Solutions
| Concentration Solvent Mass | 1 mg | 5 mg | 10 mg |
|---|
| 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 |
-
1.
Add each solvent one by one: 10% DMSO >> 90% corn oil
Solubility: ≥ 2.08 mg/mL (3.98 mM); Clear solution
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.