GSK2830371
WIP1 phosphatase inhibitor / Potent allosteric inhibitor of WIP1 phosphatase (IC50 = 6 nM), a negative regulator of the DNA damage response.1 It displayed no inhibition of 21 other phosphatases. Active in xenograft model DoHH2 B-cell lymphoma. GSK2830371 in combination with MDM2 inhibitors has been shown to be efficacious in the treatment of various cancers including liver adenocarcinoma2, acute myeloid leukemia3, and breast4. It enhances phosphorylation of the tumor suppressor p53 leading to activation.5,6
Biochemicals & reagents
1404456-53-6
1) Gilmartin et al. (2014), Allosteric Wip1 phosphatase inhibition through flap-subdomain interaction; Nat. Chem. Biol., 10 181 2) Wu et al. (2022), In vitro and in vivo study of GSK2830317 and RG7388 combination in liver adenocarcinoma; Am. J. Cancer Res., 12 4399 3) Fontana et al. (2021), Pharmacological Inhibition of WIP1 Sensitizes Acute Myeloid Leukemia Cells to the MDM2 Inhibitor Nutlin-3a; Biomedicines, 9 388 4) Pechackova et al. (2016), Inhibition of WIP1 phosphatase sensitizes breast cancer cells to genotoxic stress and to MDM2 antagonist nutlin-3; Oncotarget, 7 14458 5) Esfandiari et al. (2016), Chemical Inhibition of Wild-Type p53-Induced Phosphatase 1 (WIP1/PPM1D) by GSK2830371 Potentiates the Sensitivity to MDM2 Inhibitors in a p53-Dependent Manner; Mol. Cancer Ther., 15 379 6) Wu et al. (2021), WIP1 Inhibition by GSK2830371 Potentiates HDM201 through Enhanced p53 Phosphorylation and Activation in Liver Adenocarcinoma Cells; Cancers (Basel), 13 3876
-20°C
TARGET: Phosphatase -- PATHWAY: DNA damage; p53 -- DISEASE AREA: Cancer