Protein tyrosine phosphatase IB inhibitor

Johnson TO, ErmoUeff J, Jirousek MR. Protein tyrosine phosphatase IB inhibitors for diabetes. Nat Rev Drug Discern 2002 1 696-709. 

Boutsehs IG, Yu X, Zhang Z-Y, Borch RF. Synthesis and cell-based activity of a potent and selective protein tyrosine phosphatase IB inhibitor prodrug. J. Med. Chem. 2007 50 856-864. 

Sreenivasa, V. and Kulkarni, V.M. (2002) 3D-QSAR CoMEA and CoMSlA on protein tyrosine phosphatase IB inhibitors. Bioorg. Med. Chem., 10, 2267-2282. 

Popov D (2011) Novel protein tyrosine phosphatase IB inhibitors interaction require-... 

Dai H-L, Shen Q, Zheng J-B, Li J-Y, Wen R, Li J (2011) Synthesis and biological evaluation of novel indolin-2-one derivatives as protein tyrosine phosphatase IB inhibitors. Lett Org Chem 8 526-530... 

Peng, Y., Carroll, A.R., AddepaUi, R., Fechner, G.A., Avery, V.M., and Quitm, R.J. (2007) Vanillic acid derivatives from the green algae Cladophora socialis as potent protein tyrosine phosphatase IB inhibitors./. Nat. Prod., 70,1790-1792. 

Protein tyrosine phosphatase IB (PTP1B) inhibitor. IC5o = 4.1 pM... 

Doman TN, McGovern SL, Witherbee BJ, Kasten TP, Kurumbail R, Stallings WC, Connolly DT, Shoichet BK. Molecular docking and high throughput screening for novel inhibitors of protein tyrosine phosphatase IB. J Med Chem 2002 45 2213-21. 

The synthesis of benzo[Z>]furan derivatives has become a very active field because these molecules have been recently identified as having a variety of biological activities. For example, they can function as inhibitors of protein tyrosine phosphatase IB with antihyperglycemic properties <00JMC1293>, as well as potent and short-acting p-blockers in the treatment of various cardiovascular diseases . An inexpensive, reusable clay has been utilized to catalyze a facile cyclodehydration under microwave without solvent to form 3-substituted benzo[2>]furans from substituted a-phenoxy acetophenones 104. One of the important features of this procedure is that all the selected cyclodehydration reactions are complete in less than 10 minutes <00SL1273>. 

Liljebris et al. synthesized 2-[4-[(2amino)propyl]-2-(l(2)7/-tetrazol-5-yl)phenoxy]acetic acid 606, peptidomimetic inhibitors of protein tyrosine phosphatase IB <2002JME1785>. 

SAR-by-NMR represents a very intuitive way of rational, fragment-based drug design. Two or more independently optimized ligands of different binding sites are combined to give a high-affmity binder. The example presented here deals with the development of a selective inhibitor for the protein tyrosine phosphatase IB (PTPlB).6i... 

Mechanistically, inhibition must not necessarily block the active site itself, but it can exert allosteric effects on the substrate-binding pocket, which thereby enhances or suppresses enzymatic activity. Additional considerations regarding enzymatic reactions are discussed in Reference 86. SAR by NMR has been successfully applied to various systems [i.e., for disrupting intracellular protein-protein binding (87) as well as cytokine-receptor interaction (88)]. High-affinity enzyme inhibitors have been developed by this technique [e.g., for the metalloproteinase Stromelysin (89) and the protein tyrosine phosphatase IB (90)]. 

A series of (3-alkenylphenyldifluoromethyl)phosphonic acids (234), has been synthesized on non-crosslinked polystyrene (NCPS) support and examined for inhibition with protein tyrosine phosphatase IB. Phosphonic acid (234) was the most potent of this series of compounds being a reversible, competitive inhibitor with a K of 8.0 1,4 pM (Figure 41)." ... 

Eurther, a compound collection based on the scaffold of the natural product Euranodictin (Eigure 9.12D) revealed a previously uncharacterized inhibitor class for the protein tyrosine phosphatases PTPIB and Shp-2." A compound collection which embodies the underlying scaffold structure of alkaloid cytisine and related natural products (Figure 9.12E) revealed the first inhibitor class of the vascular endothelial protein tyrosine phosphatase (VEPTP) at a hit rate of 1.57% as well as a completely new class of inhibitors for protein tyrosine phosphatase-IB and the phosphatase Shp-2. These two enzymes are targets for the treatment of the metabolic syndrome and diabetes as well as cancer respectively. In these cases the hit rates were ca. 0.3 to 0.4%. The screens revealed selective inhibitors for the proteins." ... 

Liljebris, C., Larsen, S. D., Ogg, D., Palazuk, B. J., Bleasdale, J. E. Investigation of potential bioisosteric replacements for the carboxyl groups of peptidomimetic inhibitors of protein tyrosine phosphatase IB identification of a tetrazole-containing inhibitor with cellular activity. J. Med. Chem. 2002, 45(9), 1785-1798. 

Kotoris, C.C., Wen, W., Lough, A., and Taylor, S.D., Preparation of chiral a-monofluoroalkylphos-phonic acids and their evaluation as inhibitors of protein tyrosine phosphatase IB, 7. Chem. Soc.. Perkin Trans. 1, 1271, 2000. 

Yokomatsu, T., Murano, T.. Umesue. 1., Soeda, S., Shrmeno, H., and Shibuya. S., Synthesis and biological evaluation of a.a-dilluorobenzylphosphonic acid derivatives as small molecular inhibitors of protein-tyrosine phosphatase IB, Bioorg. Med. Chem. Lett., 9, 529. 1999. 

Patankar, S.J. and Jurs, P.C. (2003b) Classification of inhibitors of protein tyrosine phosphatase IB using molecular structure based descriptors. 

Maccari R, Ottana R, Ciurleo R et al (2009) Structure-based optimization of benzoic acids as inhibitors of protein tyrosine phosphatase IB and low molecular weight protein tyrosine phosphatase. ChemMedChem 4 957-962... 

Asante-Appiah E, Patel S, Desponts C et al (2006) Conformation-assisted inhibition of protein-tyrosine phosphatase-IB elicits inhibitor selectivity over T-ceU protein-tyrosine phosphatase. J Biol Chem 281 8010-8015... 

Puius YA, Zhao Y, Sullivan M et al (1997) Identification of a second aryl phosphate-binding site in protein-tyrosine phosphatase IB a paradigm for inhibitor design. Proc Natl Acad Sci U S A 94 13420-13425... 

Lee S, Wang Q (2007) Recent development of small molecular specific inhibitor of protein tyrosine phosphatase IB. Med Res Rev 27 553-573... 

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