Inhibitors of the lipid phosphatase SHIP2 discovered by high throughput affinity selection-mass spectrometry screening of combinatorial libraries

Combinatorial Chemistry and High Throughput Screening

Volumn 12, Issue 8, 2009, Pages 760-771

  Annis, D Allen ^a,c   Cheng, Cliff C ^a,d   Chuang, Cheng Chi ^a,d   McCarter, John D ^b   Nash, Huw M ^a,c   Nazef, Naim ^a   Rowe, Todd ^b   Kurzeja, Robert J M ^b   Shipps Jr , Gerald W ^a,d  

^a NeoGenesis Drug Discovery   (United States)

^b AMGEN INC   (United States)

^c Aileron Therapeutics Inc   (United States)

^d MERCK RESEARCH LABORATORIES   (United States)

Author keywords

Affinity selection; ALIS; High throughput screening; Label free; Mass spectrometry; SHIP2

Indexed keywords

ENZYME INHIBITOR; LIGAND; LIPID PHOSPHATASE SHIP2; NGD 61338; PHOSPHATASE; PHOSPHATIDYLINOSITOL 3,4,5 TRISPHOSPHATE; UNCLASSIFIED DRUG;

ARTICLE; BINDING AFFINITY; COMBINATORIAL LIBRARY; DRUG INHIBITION; DRUG RECEPTOR BINDING; ENZYME ACTIVE SITE; ENZYME ACTIVITY; EXPERIMENT; HIGH THROUGHPUT SCREENING; MASS SPECTROMETRY; MEASUREMENT; NON INSULIN DEPENDENT DIABETES MELLITUS; PRIORITY JOURNAL; QUANTITATIVE ANALYSIS; STRUCTURE ACTIVITY RELATION; SYNTHESIS;

CATALYTIC DOMAIN; COMBINATORIAL CHEMISTRY TECHNIQUES; ENZYME INHIBITORS; HIGH-THROUGHPUT SCREENING ASSAYS; MASS SPECTROMETRY; MOLECULAR STRUCTURE; PHOSPHORIC MONOESTER HYDROLASES; PYRAZOLES; STEREOISOMERISM; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 69749122834     PISSN: 13862073     EISSN: None     Source Type: Journal    
DOI: 10.2174/138620709789104870     Document Type: Article

References (23)

1. Lazar, D.F.; Saltiel, A.R. Lipid phosphatases as drug discovery targets for type 2 diabetes. Nat. Rev. Drug. Discov., 2006, 5, 333-342.
2. Drees, B.E.; Weipert, A.; Hudson, H.; Ferguson, C.G.; Chakravarty, L.; Prestwich, G.D. Competitive fluorescence polarization assays for the detection of phosphoinositide kinase and phosphatase activity. Comb. Chem. High. Throughput. Screen. 2003, 6, 321-330.
3. Rowe, T.; Hale, C.; Zhou, A.; Kurzeja, R.J.; Ali, A.; Menjares, A.; Wang, M.; McCarter, J.D. A high throughput microfluidic assay for SH2 domain-containing inositol 5-phosphatase 2. Assay. Drug. Dev. Technol., 2006, 4, 175-183.
4. Dufresne, C.; Roy, P.; Wang, Z.; Asante-Appiah, E.; Cromlish, W.; Boie, Y.; Forghani, F.; Desmarais, S.; Wang, Q.; Skorey, K.; Waddleton, D.; Ramachandran, C.; Kennedy, B.P.; Xu, L.; Gordon, R.; Chan, C.C.; Leblanc, Y. The development of potent nonpeptidic PTP-1B inhibitors. Bioorg. Med. Chem. Lett., 2004, 14, 1039-1042. (Pubitemid 38167638)
5. Annis, D.A.; Chuang, C.C.; Nazef, N. ALIS: An affinity selection- mass spectrometry system for the discovery and characterization of protein-ligand interactions. In Mass Spectrometry in Medicinal Chemistry. Wanner, K.; Höfner, G.; Eds.; Wiley-VCH; 2007, pp. 121-184. [Mannhold R, Kubinyi H, Folkers G (Series Editor): Methods and Principles in Medicinal Chemistry].
6. Annis, D.A.; Nickbarg, E.; Yang, X.; Ziebell, M.R.; Whitehurst, C.E. Affinity selection-mass spectrometry screening techniques for small molecule drug discovery. Curr. Opin. Chem. Biol., 2007, 11, 518-526.
7. Falb, D.; Jindal, S. Chemical genomics: bridging the gap between the proteome and therapeutics. Curr. Opin. Drug. Discov. Devel., 2002, 5, 532-539. (Pubitemid 36748983)
8. Annis, A.; Athanasopoulos, J.; Curran P.J.; Felsch J.S.; Kalghatgi, K.; Lee, W.H.; Nash H.M.; Orminati, J.P.A.; Rosner, K.E.; Shipps, Jr. G.W.; Thaddupathy, G.R.A.; Tyler, A.N.; Vilenchik, L.; Wagner, C.R,; Wintner, E.A.An affinity selection-mass spectrometry method for the identification of small molecule ligands from self-encoded combinatorial libraries: discovery of a novel antagonist of E. coli dihydrofolate reductase. Int. J. Mass. Spectrom., 2004, 238, 77-83.
9. Annis, D.A.; Shipps, G.W.; Jr., Deng, Y.; Popovici-Muller, J.; Siddiqui, M.A.; Curran, P.J.; Gowen, M.; Windsor, W.T. Method for quantitative protein-ligand affinity measurements in compound mixtures. Anal. Chem., 2007, 79, 4538-4542.
10. Coburn, C.A.; Stachel, S.J.; Li, Y.M.; Rush, D.M.; Steele, T.G.; Chen-Dodson, E.; Holloway, M.K.; Xu, M.; Huang, Q.; Lai, M.T.; DiMuzio, J.; Crouthamel, M.C.; Shi, X.P.; Sardana, V.; Chen, Z.; Munshi, S.; Kuo, L.; Makara, G.M.; Annis, D.A.; Tadikonda, P.K.; Nash, H.M.; Vacca, J.P.; Wang, T. Identification of a small molecule nonpeptide active site beta-secretase inhibitor that displays a nontraditional binding mode for aspartyl proteases. J. Med. Chem., 2004, 47, 6117-6119. (Pubitemid 39587236)
11. Whitehurst, C.E.; Nazef, N.; Annis, D.A.; Hou, Y.; Murphy, D.M.; Spacciapoli, P.; Yao, Z.; Ziebell, M.R.; Cheng, C.C.; Shipps, G.W. Jr.; Felsch, J.S.; Lau, D.; Nash, H.M. Discovery and characterization of orthosteric and allosteric muscarinic M2 acetylcholine receptor ligands by affinity selection-mass spectrometry. J. Biomol. Screen. 2006, 11, 194-207.
12. Whitehurst, C.E.; Annis, D.A. Affinity selection-mass Spectrometry and its emerging application to the high throughput screening of G-protein-coupled receptors. Comb. Chem. High. Throughput. Screen. 2008, 11, 427-438
13. Christopoulos, A.; May, L.T.; Avlani, V.A.; Sexton, P.M. Gprotein- coupled receptor allosterism: the promise and the problem(s).Allosteric modulators of G-protein-coupled receptors. Biochem. Soc. Trans., 2004, 32, 873-877.
14. May, L.T.; Christopoulos, A. Allosteric modulators of G-proteincoupled receptors. Curr. Opin. Pharmacol., 2003, 3, 551-556.
15. May, L.T.; Leach, K.; Sexton, P.M.; Christopoulos, A. Allosteric modulation of G protein-coupled receptors. Annu. Rev. Pharmacol. Toxicol., 2007, 47, 1-51.
16. Each sample also contained 50 mM, pH 7.5 HEPES-buffered saline containing 150 mM NaCl, 2 mM DTT, 0.5 mM EGTA, 1.25 mM MgCl2 and 2.5% DMSO.
17. SEC mobile phase is 50 mM, pH 7.5 HEPES-buffered saline containing 350 mM NaCl.
18. Makara, G.M.; Nash, H.; Zheng, Z.; Orminati, J.P.; Wintner, E.A. A reagent-based strategy for the design of large combinatorial libraries: a preliminary experimental validation. Mol. Divers., 2003, 7, 3-14.
19. Nash, H. N.; Birnbaum, S.; Wintner, E. A.; Kalghatgi, K.; Shipps, G. W., Jr.; Jindal, S. U.S. Patent 6,207,861, 2001.
20. Nicolaou, K.C.; Pfefferkorn, J.A.; Barluenga, S.; Mitchell, H.J.; Roecker, A.J.; Cao, G.Q. Natural product-like combinatorial libraries based on privileged structures. 3. The "libraries from libraries" principle for diversity enhancement of benzopyran libraries. J. Am. Chem. Soc., 2000, 122, 9968-9976.
21. Annis, D.A.; Nazef, N.; Chuang, C.C.; Scott, M.P.; Nash, H.M. A general technique to rank protein-ligand binding affinities and determine allosteric versus direct binding site competition in compound mixtures. J. Am. Chem. Soc., 2004, 126, 15495-15503.
22. Ehlert, F.J. Estimation of the affinities of allosteric ligands using radioligand binding and pharmacological null methods. Mol. Pharmacol., 1988, 33, 187-194.
23. This function is readily amenable to nonlinear regression analysis using commercially available software: Mathematica 6.0, 2007. Wolfram Research, Champaign, IL. www.wolfram.com