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].
IC50 & Target[3]
GLUT1
115 nM (IC50)
GLUT2
137 nM (IC50)
GLUT3
90 nM (IC50)
GLUT4
68 nM (IC50)
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 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].
上海金畔生物科技有限公司 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.
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 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].
上海金畔生物科技有限公司 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.
分子量
522.60
Formula
C30H30N6O3
CAS 号
1369452-53-8
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
溶解性数据
In Vitro:
DMSO : 25 mg/mL (47.84 mM; ultrasonic and warming and heat to 60°C)
[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.
SEC inhibitor KL-2 (KL-2), a peptidomimetic lead compound, is a potent, selective super elongation complex (SEC) inhibitor and disrupts the interaction between the SEC scaffolding protein AFF4 and P-TEFb, resulting in impaired release of Pol II from promoter-proximal pause sites and a reduced average rate of processive transcription elongation. SEC inhibitor KL-2 exhibits an dose-dependent inhibitory effect on AFF4-CCNT1 interaction with a Ki of 1.50 μM[1].
IC50 & Target
SEC[1]
分子量
333.74
Formula
C17H13ClFNO3
CAS 号
900308-51-2
运输条件
Room temperature in continental US; may vary elsewhere.
SEC inhibitor KL-1 (KL-1), a peptidomimetic lead compound, is a potent, selective super elongation complex (SEC) inhibitor and disrupts the interaction between the SEC scaffolding protein AFF4 and P-TEFb, resulting in impaired release of Pol II from promoter-proximal pause sites and a reduced average rate of processive transcription elongation. SEC inhibitor KL-1 exhibits an dose-dependent inhibitory effect on AFF4-CCNT1 interaction with a Ki of 3.48 μM[1].
IC50 & Target
SEC[1]
分子量
345.78
Formula
C18H16ClNO4
CAS 号
900308-84-1
运输条件
Room temperature in continental US; may vary elsewhere.
