KL-11743

本公司产品仅用于科研实验，不得用于人体或动物的临床与诊断

KL-11743 特异性阻断葡萄糖代谢，引发 NADH 池的急性崩溃和天冬氨酸的显着积累，表明线粒体中向氧化磷酸化的急剧转变。

KL-11743 specifically blocks glucose metabolism, triggering an acute collapse in NADH pools and a striking accumulation of aspartate, indicating a dramatic shift toward oxidative phosphorylation in the mitochondria.(In Vitro):Patient-derived xenograft models of succinate dehydrogenase A (SDHA)-deficient cancers are specifically sensitive to KL-11743, providing direct evidence that TCA cycle-mutant tumors are vulnerable to GLUT inhibitors in vivo.

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.KL-11743 (39-10000 nM; 24-72 h) dose-dependently inhibits the growth of HT-1080 cells, with an IC50 of 677 nM.KL-11743 inhibits the growth of KEAP1-mutant lung cancer cells with more potency compared to KEAP1-WT lung cancer cells.KL-11743 (0.001-10 μM) induces a rapid increase in the phosphorylation of AMPK and acetyl-coenzyme A carboxylase in HT-1080 cells .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).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. Cell Viability Assay Cell Line:HT-1080 cells Concentration:39, 78, 156, 312, 625, 1250, 2500, 5000, 10000 nMIncubation Time:24, 48, 72 hoursResult:Inhibited the growth of HT-1080 cells in a dose-dependent manner.

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.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.KL-11743 significantly suppresses the growth of KEAP1 KO tumors.Plasma levels of KL-11743 (100 mg/kg; i.p.) are maintained at inhibitory levels for most of the 24-hour dosing period.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).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.). Animal Model:4 to 6-week-old athymic nude mice (Foxn1nu/Foxn1nu) were injected with NCI-H226 cells.100 mg/kg 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.

——

Others

Other Targets

——

——

——

1369452-53-8

522.609

C30H30N6O3

>98% (HPLC)

In Vitro:?DMSO : 25 mg/mL (47.84 mM)

CCOc1ccc2nc(nc(Nc3ccc(cc3)-c3cn[nH]c3)c2c1)-c1cccc(OCC(=O)NC(C)C)c1

——

(-20℃)

With Ice Pack

≥ 2 years