For research use only. Not for therapeutic Use.
VER-246608 is a potent and ATP-competitive inhibitor of pyruvate dehydrogenase kinase (PDK) with IC50s of 35 nM, 40 nM, 84 nM, and 91 nM for PDK-1, PDK-3, PDK-2, and PDK-4, respectively.
VER-246608 is a novel pan-isoform ATP competitive inhibitor of PDK. VER-246608 demonstrates similar potency across all four PDK isoforms in a DELFIA-based enzyme functional assay in the sub 100 nM range. In terms of cellular biomarker modulation, VER-246608 suppresses the phosphorylation of the Ser293 residue of E1α (phosphorylated by all four PDK isozymes) with IC50 values of 266 nM. Treatment of PC-3 cells with 9 μM and 27 μM VER-246608 results in a 21% and 42% reduction, respectively, in media L-lactate levels following a 1 h incubation. VER-246608 also decreases D-glucose consumption at the same concentrations that result in reduced L-lactate production. An approximately 50% reduction in spheroid volume is achieved at concentrations of 10 μM and above, suggesting an increase in VER-246608 potency compared to monolayer growth[1].
| Catalog Number | I010013 |
| CAS Number | 1684386-71-7 |
| Synonyms | N-[4-(2-chloro-5-methylpyrimidin-4-yl)phenyl]-N-[[4-[[(2,2-difluoroacetyl)amino]methyl]phenyl]methyl]-2,4-dihydroxybenzamide |
| Molecular Formula | C28H23ClF2N4O4 |
| Purity | ≥95% |
| InChI | InChI=1S/C28H23ClF2N4O4/c1-16-13-33-28(29)34-24(16)19-6-8-20(9-7-19)35(27(39)22-11-10-21(36)12-23(22)37)15-18-4-2-17(3-5-18)14-32-26(38)25(30)31/h2-13,25,36-37H,14-15H2,1H3,(H,32,38) |
| InChIKey | LCGNLQSOSJFLKR-UHFFFAOYSA-N |
| SMILES | CC1=CN=C(N=C1C2=CC=C(C=C2)N(CC3=CC=C(C=C3)CNC(=O)C(F)F)C(=O)C4=C(C=C(C=C4)O)O)Cl |
| Reference | [1]. Moore JD, et al. VER-246608, a novel pan-isoform ATP competitive inhibitor of pyruvate dehydrogenase kinase, disrupts Warburg metabolism and induces context-dependent cytostasis in cancer cells. Oncotarget. 2014 Dec 30;5(24):12862-76. |
