Using small molecules to target protein phosphatases.

Article Details


Vintonyak VV, Waldmann H, Rauh D

Using small molecules to target protein phosphatases.

Bioorg Med Chem. 2011 Apr 1;19(7):2145-55. doi: 10.1016/j.bmc.2011.02.047. Epub 2011 Mar 2.

PubMed ID
21420867 [ View in PubMed

The site specific functionalization of phosphate groups with amino acid side chains of substrate proteins represents one of the most important regulatory mechanisms of biological systems. Phosphorylation and dephosphorylation are reversibly catalyzed by protein kinases and protein phosphatases, and the aberrant regulation of these enzymes is associated with the onset and progression of various disease states such as cancer, diabetes, neurodegenerative and autoimmune disorders, making these proteins attractive targets for drug discovery. Here we report on strategies currently explored for the identification and development of various inhibitors directed against clinically relevant phosphatases. While over the last years, inhibition of phosphorylation has evolved into a key strategy in targeted therapies, the development of clinically relevant phosphatase inhibitors still faces major bottlenecks and is often plagued by limited selectivity and unfavorable pharmacokinetics. The reader will gain a better understanding of the importance of the field and its current limitations.

DrugBank Data that Cites this Article

Binding Properties
DrugTargetPropertyMeasurementpHTemperature (°C)
1,2,5-THIADIAZOLIDIN-3-ONE-1,1-DIOXIDETyrosine-protein phosphatase non-receptor type 1IC 50 (nM)1600000N/AN/ADetails
3-(3,5-Dibromo-4-Hydroxy-Benzoyl)-2-Ethyl-Benzofuran-6-Sulfonic Acid [4-(Thiazol-2-Ylsulfamoyl)-Phenyl]-AmideTyrosine-protein phosphatase non-receptor type 1IC 50 (nM)8000N/AN/ADetails
4-[3-(dibenzylamino)phenyl]-2,4-dioxobutanoic acidTyrosine-protein phosphatase non-receptor type 1IC 50 (nM)20000N/AN/ADetails
5-(4-METHOXYBIPHENYL-3-YL)-1,2,5-THIADIAZOLIDIN-3-ONE 1,1-DIOXIDETyrosine-protein phosphatase non-receptor type 1IC 50 (nM)2500N/AN/ADetails