| Description |
JX06 is a potent, selective and covalent inhibitor of PDK. JX06 inhibits PDK1, PDK2 and PDK3 with the IC50s of 49 nM, 101 nM, and 313 nM, respectively. JX06 inhibits PDK1 activity via covalently binding to a cysteine residue in an irreversible manner. JX06 shows significant antitumor activity[1].
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| Related Catalog |
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| Target |
IC50: 49 nM (PDK1), 101 nM (PDK2), 313 nM (PDK3)[1]
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| In Vitro |
JX06 barely shows inhibitory activity against PDK4 at a concentration of 10 μM[1]. JX06 (1-10 μM; 48 hours) induces cell apoptosis in cancer cells with high ECAR/OCR[1]. JX06 (0-0.6 μM; 72 hours) dose-dependently suppresses the growth of A549 cells[1]. JX06 (0.1-10 μM; 6-24 hours) inhibits PDHA1 phosphorylation in A549 cells in a time- and dose-dependent manner[1]. JX06 (1-10 μM) increases glucose uptake and intracellular ATP level and reduces aerobic glycolysis determined by the lactate production in A549 cells[1]. JX06 (1-10 μM; 24 hours) induces ROS generation in cancer cells with high extracellular acidification rate (ECAR)/ oxygen consumption rate (OCR) [1]. Apoptosis Analysis[1] Cell Line: A549, EBC-1, HT-29 and H460 cells Concentration: 0, 1, 3, 10 μM Incubation Time: 48 hours Result: Induces cell apoptosis in A549 and EBC-1 cells. Cell Viability Assay[1] Cell Line: A549 cells Concentration: 0, 0.2, 0.4, 0.6 μM Incubation Time: 72 hours Result: Inhibits the viability of A549 cells in a dose dependent manner. Western Blot Analysis[1] Cell Line: A549 cells Concentration: 0, 0.1, 0.3, 1, 3, 10 μM Incubation Time: 0, 6, 12, 24 hours Result: Decreased PDHA1 phosphorylation at both serine 293 and serine 232 (S293 and S232) in a time- and dose-dependent manner.
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| In Vivo |
JX06 (40-80 mg/kg; i.p. for 21 days) inhibits tumor growth in vivo[1]. Animal Model: A549 subcutaneous xenograft mice[1] Dosage: 40, 80 mg/kg Administration: I.p. injections for 21 days Result: Reduced tumor weights and 67.5% tumor volume at the dose of 80 mg/kg compared with the vehicle control. Well tolerated at the administration dose.
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| References |
[1]. Wenyi S, et, al. JX06 Selectively Inhibits Pyruvate Dehydrogenase Kinase PDK1 by a Covalent Cysteine Modification. Cancer Res. 2015 Nov 15; 75(22): 4923-36.
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