Advancing biological understanding and therapeutics discovery with small-molecule probes

Cell

Volumn 161, Issue 6, 2015, Pages 1252-1265

  Schreiber, Stuart L ^a,b   Kotz, Joanne D ^a   Li, Min ^c,o   Aubé, Jeffrey ^d   Austin, Christopher P ^e,f   Reed, John C ^g,p   Rosen, Hugh ^h,i   White, E Lucile ^j   Sklar, Larry A ^k,l   Lindsley, Craig W ^m,n   Alexander, Benjamin R ^a   Bittker, Joshua A ^a   Clemons, Paul A ^a   De Souza, Andrea ^a   Foley, Michael A ^a,q   Palmer, Michelle ^a   Shamji, Alykhan F ^a   Wawer, Mathias J ^a   McManus, Owen ^c   Wu, Meng ^c,r   Zou, Beiyan ^c   Yu, Haibo ^c   Golden, Jennifer E ^d   Schoenen, Frank J ^d   Simeonov, Anton ^e,f   Jadhav, Ajit ^e,f   Jackson, Michael R ^g   Pinkerton, Anthony B ^g   Chung, Thomas D Y ^g   Griffin, Patrick R ^h,i   Cravatt, Benjamin F ^h,i   Hodder, Peter S ^h,i,s   Roush, William R ^h,i   Roberts, Edward ^h,i   Chung, Dong Hoon ^j,t   Jonsson, Colleen B ^j,u   Noah, James W ^j,w   Severson, William E ^j,v   Ananthan, Subramaniam ^j   Edwards, Bruce ^k,l   Oprea, Tudor I ^k,l   Conn, P Jeffrey ^m,n   Hopkins, Corey R ^m,n   Wood, Michael R ^m,n   Stauffer, Shaun R ^m   Emmitte, Kyle A ^m,n   more..

^a MASSACHUSETTS INSTITUTE OF TECHNOLOGY   (United States)

^b HARVARD UNIVERSITY   (United States)

^c JOHNS HOPKINS UNIVERSITY SCHOOL OF MEDICINE   (United States)

^d UNIVERSITY OF KANSAS   (United States)

^e NATIONAL INSTITUTES OF HEALTH   (United States)

^f NATIONAL INSTITUTES OF HEALTH   (United States)

^g BURNHAM INSTITUTE   (United States)

^h SCRIPPS RESEARCH INSTITUTE   (United States)

ⁱ SCRIPPS RESEARCH INSTITUTE   (United States)

^j SOUTHERN RESEARCH INSTITUTE   (United States)

^k UNIVERSITY OF NEW MEXICO   (United States)

^l UNIVERSITY OF NEW MEXICO SCHOOL OF MEDICINE   (United States)

^m VANDERBILT UNIVERSITY MEDICAL CENTER   (United States)

ⁿ VANDERBILT UNIVERSITY SCHOOL OF MEDICINE   (United States)

^o GLAXOSMITHKLINE   (United States)

^p F HOFFMANN LA ROCHE LTD   (Switzerland)

^q Tri Institutional Therapeutics Discovery Institute Inc   (United States)

^r UNIVERSITY OF IOWA   (United States)

^s AMGEN INC   (United States)

^t University of Louisville School of Medicine   (United States)

^u UNIVERSITY OF TENNESSEE   (United States)

^v UNIVERSITY OF LOUISVILLE   (United States)

^w National Biodefense Analysis and Countermeasures Center   (United States)

more..

Author keywords

[No Author keywords available]

Indexed keywords

ADENOSINE TRIPHOSPHATASE INHIBITOR; ANTIDIABETIC AGENT; ANTIVIRUS AGENT; FINGOLIMOD; G PROTEIN COUPLED RECEPTOR; GUANOSINE TRIPHOSPHATASE; HYDROLASE INHIBITOR; ML 007; ML 108; ML 165; ML 198; ML 238; ML 240; ML 253; ML 341; MUSCARINIC RECEPTOR; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR GAMMA; REDUCED NICOTINAMIDE ADENINE DINUCLEOTIDE (PHOSPHATE) DEHYDROGENASE (QUINONE); RNA BINDING PROTEIN; ROSIGLITAZONE; SPHINGOSINE 1 PHOSPHATE RECEPTOR; UNCLASSIFIED DRUG; ENZYME INHIBITOR; MOLECULAR LIBRARY;

ARTICLE; BINDING SITE; BIOLOGICAL ACTIVITY; CELL PROLIFERATION; CHAGAS DISEASE; CHEMICAL STRUCTURE; DRUG DEVELOPMENT; DRUG EFFICACY; GENE EXPRESSION; HUMAN; MOLECULAR LIBRARY; NONHUMAN; PRIORITY JOURNAL; PROTEIN PHOSPHORYLATION; STEREOISOMERISM; STRUCTURE ACTIVITY RELATION; ANIMAL; CHEMISTRY; HIGH THROUGHPUT SCREENING; NATIONAL HEALTH ORGANIZATION; UNITED STATES;

ANIMALS; DRUG DISCOVERY; ENZYME INHIBITORS; HIGH-THROUGHPUT SCREENING ASSAYS; HUMANS; NATIONAL INSTITUTES OF HEALTH (U.S.); SMALL MOLECULE LIBRARIES; UNITED STATES;

EID: 84932611992     PISSN: 00928674     EISSN: 10974172     Source Type: Journal    
DOI: 10.1016/j.cell.2015.05.023     Document Type: Review

References (98)

1. Adibekian, A., Martin, B.R., Chang, J.W., Hsu, K.L., Tsuboi, K., Bachovchin, D.A., Speers, A.E., Brown, S.J., Spicer, T., Fernandez-Vega, V., et al. (2012). Confirming target engagement for reversible inhibitors in vivo by kinetically tuned activity-based probes. J. Am. Chem. Soc. 134, 10345-10348.
2. Anastasiou, D., Yu, Y., Israelsen, W.J., Jiang, J.K., Boxer, M.B., Hong, B.S., Tempel, W., Dimov, S., Shen, M., Jha, A., et al. (2012). Pyruvate kinase M2 activators promote tetramer formation and suppress tumorigenesis. Nat. Chem. Biol. 8, 839-847.
3. Arrowsmith, J. (2011a). Trial watch: Phase II failures: 2008-2010. Nat. Rev. Drug Discov. 10, 328-329.
4. Arrowsmith, J. (2011b). Trial watch: phase III and submission failures: 2007-2010. Nat. Rev. Drug Discov. 10, 87.
5. Aubert, R.E., Herrera, V., Chen, W., Haffner, S.M., and Pendergrass, M. (2010). Rosiglitazone and pioglitazone increase fracture risk in women and men with type 2 diabetes. Diabetes Obes. Metab. 12, 716-721.
6. Austin, C.P., Brady, L.S., Insel, T.R., and Collins, F.S. (2004). NIH Molecular Libraries Initiative. Science 306, 1138-1139.
7. Bachovchin, D.A., Brown, S.J., Rosen, H., and Cravatt, B.F. (2009). Identification of selective inhibitors of uncharacterized enzymes by high-throughput screening with fluorescent activity-based probes. Nat. Biotechnol. 27, 387-394.
8. Bachovchin, D.A., Mohr, J.T., Speers, A.E., Wang, C., Berlin, J.M., Spicer, T.P., Fernandez-Vega, V., Chase, P., Hodder, P.S., Schürer, S.C., et al. (2011). Academic cross-fertilization by public screening yields a remarkable class of protein phosphatase methylesterase-1 inhibitors. Proc. Natl. Acad. Sci. USA 108, 6811-6816.
9. Baell, J., and Walters, M.A. (2014). Chemistry: Chemical con artists foil drug discovery. Nature 513, 481-483.
10. Begley, C.G., and Ellis, L.M. (2012). Drug development: Raise standards for preclinical cancer research. Nature 483, 531-533.
11. Bern, C. (2011). Antitrypanosomal therapy for chronic Chagas' disease. N. Engl. J. Med. 364, 2527-2534.
12. Boxer, M.B., Jiang, J.K., Vander Heiden, M.G., Shen, M., Skoumbourdis, A.P., Southall, N., Veith, H., Leister, W., Austin, C.P., Park, H.W., et al. (2010). Evaluation of substituted N,N'-diarylsulfonamides as activators of the tumor cell specific M2 isoform of pyruvate kinase. J. Med. Chem. 53, 1048-1055.
13. Bridges, T.M., Reid, P.R., Lewis, L.M., Dawson, E.S., Weaver, C.D., Wood, M.R., and Lindsley, C.W. (2010). Discovery and development of a second highly selective M1 Positive Allosteric Modulator (PAM). In Probe Reports from the NIH Molecular Libraries Program (National Center for Biotechnology Information).
14. Carmody, L.C., Germain, A.R., Engel, J.C., Gut, J., Kaiser, M., Jewett, I., Le-Quemen, S., Marie, J.C., Dandapani, S., Rodriguez, A., et al. (2010). Identification of Diversity-Oriented Synthesis Derived Small Molecule, ML341, with Cidal Activity Against Trypanosoma cruzi. In Probe Reports from the NIH Molecular Libraries Program (National Center for Biotechnology Information).
15. Chen, J.K., Lane, W.S., and Schreiber, S.L. (1999). The identification of myriocin-binding proteins. Chem. Biol. 6, 221-235.
16. Choi, J.H., Banks, A.S., Estall, J.L., Kajimura, S., Boström, P., Laznik, D., Ruas, J.L., Chalmers, M.J., Kamenecka, T.M., Blüher, M., et al. (2010). Anti-diabetic drugs inhibit obesity-linked phosphorylation of PPARgamma by Cdk5. Nature 466, 451-456.
17. Choi, J.H., Banks, A.S., Kamenecka, T.M., Busby, S.A., Chalmers, M.J., Kumar, N., Kuruvilla, D.S., Shin, Y., He, Y., Bruning, J.B., et al. (2011). Antidiabetic actions of a non-agonist PPARg ligand blocking Cdk5-mediated phosphorylation. Nature 477, 477-481.
18. Choi, J.H., Choi, S.S., Kim, E.S., Jedrychowski, M.P., Yang, Y.R., Jang, H.J., Suh, P.G., Banks, A.S., Gygi, S.P., and Spiegelman, B.M. (2014). Thrap3 docks on phosphoserine 273 of PPARg and controls diabetic gene programming. Genes Dev. 28, 2361-2369.
19. Christofk, H.R., Vander Heiden, M.G., Harris, M.H., Ramanathan, A., Gerszten, R.E., Wei, R., Fleming, M.D., Schreiber, S.L., and Cantley, L.C. (2008). The M2 splice isoform of pyruvate kinase is important for cancer metabolism and tumour growth. Nature 452, 230-233.
20. Conn, P.J., Christopoulos, A., and Lindsley, C.W. (2009a). Allosteric modulators of GPCRs: a novel approach for the treatment of CNS disorders. Nat. Rev. Drug Discov. 8, 41-54.
21. Conn, P.J., Jones, C.K., and Lindsley, C.W. (2009b). Subtype-selective allosteric modulators of muscarinic receptors for the treatment of CNS disorders. Trends Pharmacol. Sci. 30, 148-155.
22. Dandapani, S., Germain, A.R., Jewett, I., le Quement, S., Marie, J.C., Muncipinto, G., Duvall, J.R., Carmody, L.C., Perez, J.R., Engel, J.C., et al. (2014). Diversity-oriented synthesis yields a new drug lead for treatment of chagas disease. ACS Med Chem Lett 5, 149-153.
23. Dillon, M.B., Bachovchin, D.A., Brown, S.J., Finn, M.G., Rosen, H., Cravatt, B.F., and Mowen, K.A. (2012). Novel inhibitors for PRMT1 discovered by high-throughput screening using activity-based fluorescence polarization. ACS Chem. Biol. 7, 1198-1204.
24. Edwards, A.M., Arrowsmith, C.H., Bountra, C., Bunnage, M.E., Feldmann, M., Knight, J.C., Patel, D.D., Prinos, P., Taylor, M.D., and Sundström, M.; SGC Open Source Target-Discovery Partnership (2015). Preclinical target validation using patient-derived cells. Nat. Rev. Drug Discov. 14, 149-150.
25. Edwards, A.M., Isserlin, R., Bader, G.D., Frye, S.V., Willson, T.M., and Yu, F.H. (2011). Too many roads not taken. Nature 470, 163-165.
26. Fidock, D.A. (2013). Microbiology. Eliminating malaria. Science 340, 1531-1533.
27. Frye, S.V. (2010). The art of the chemical probe. Nat. Chem. Biol. 6, 159-161.
28. Gentry, P.R., Bridges, T.M., Daniels, J.S., Lamsal, A., Vinson, P.N., Niswender, C.M., Hodder, P.S., Rosen, H., Conn, P.J., Engers, J., et al. (2010). Development and characterization of a highly selective M5 PAM probe molecule with improved potency. In Probe Reports from the NIH Molecular Libraries Program (National Center for Biotechnology Information).
29. Gentry, P.R., Bridges, T.M., Lamsal, A., Vinson, P.N., Smith, E., Chase, P., Hodder, P.S., Engers, J.L., Niswender, C.M., Daniels, J.S., et al. (2013). Discovery of ML326: The first sub-micromolar, selective M5 PAM. Bioorg. Med. Chem. Lett. 23, 2996-3000.
30. Gerard, B., Duvall, J.R., Lowe, J.T., Murillo, T., Wei, J., Akella, L.B., and Marcaurelle, L.A. (2011). Synthesis of a stereochemically diverse library of medium-sized lactams and sultams via S(N)Ar cycloetherification. ACS Comb Sci 13, 365-374.
31. Goldin, E., Zheng, W., Motabar, O., Southall, N., Choi, J.H., Marugan, J., Austin, C.P., and Sidransky, E. (2012). High throughput screening for small molecule therapy for Gaucher disease using patient tissue as the source of mutant glucocerebrosidase. PLoS ONE 7, e29861.
32. Gonzalez-Cabrera, P.J., Jo, E., Sanna, M.G., Brown, S., Leaf, N., Marsolais, D., Schaeffer, M.T., Chapman, J., Cameron, M., Guerrero, M., et al. (2008). Full pharmacological efficacy of a novel S1P1 agonist that does not require S1P-like headgroup interactions. Mol. Pharmacol. 74, 1308-1318.
33. Guerrero, M., Poddutoori, R., Pinacho-Crisostomo, F., Schaeffer, M.T., Brown, S.J., Spicer, T., Chase, P., Ferguson, J., Roberts, E., Sanna, G., et al. (2010a). Probe Development Efforts for an Allosteric Agonist of the Sphingosine 1-phosphate Receptor 3 (S1P3). In Probe Reports from the NIH Molecular Libraries Program (National Center for Biotechnology Information).
34. Guerrero, M., Urbano, M., Velaparthi, S., Schaeffer, M.T., Brown, S.J., Crisp, M., Ferguson, J., Hodder, P., Rosen, H., Oldstone, M., and Roberts, E. (2010b). Identification of a Novel Agonist of the Sphingosine 1-phosphate Receptor 4 (S1P4). In Probe Reports from the NIH Molecular Libraries Program (National Center for Biotechnology Information).
35. Guerrero, M., Urbano, M., Velaparthi, S., Zhao, J., Schaeffer, M.T., Brown, S., Rosen, H., and Roberts, E. (2011). Discovery, design and synthesis of the first reported potent and selective sphingosine-1-phosphate 4 (S1P4) receptor antagonists. Bioorg. Med. Chem. Lett. 21, 3632-3636.
36. Guerrero, M., Urbano, M., Zhao, J., Crisp, M., Chase, P., Hodder, P., Schaeffer, M.T., Brown, S., Rosen, H., and Roberts, E. (2012). Discovery, design and synthesis of novel potent and selective sphingosine-1-phosphate 4 receptor (S1P4-R) agonists. Bioorg. Med. Chem. Lett. 22, 537-542.
37. Gustafsdottir, S.M., Ljosa, V., Sokolnicki, K.L., Anthony Wilson, J., Walpita, D., Kemp, M.M., Petri Seiler, K., Carrel, H.A., Golub, T.R., Schreiber, S.L., et al. (2013). Multiplex cytological profiling assay to measure diverse cellular states. PLoS ONE 8, e80999.
38. Hanson, M.A., Roth, C.B., Jo, E., Griffith, M.T., Scott, F.L., Reinhart, G., Desale, H., Clemons, B., Cahalan, S.M., Schuerer, S.C., et al. (2012). Crystal structure of a lipid G protein-coupled receptor. Science 335, 851-855.
39. Hay, M., Thomas, D.W., Craighead, J.L., Economides, C., and Rosenthal, J. (2014). Clinical development success rates for investigational drugs. Nat. Biotechnol. 32, 40-51.
40. Heidebrecht, R.W., Jr., Mulrooney, C., Austin, C.P., Barker, R.H., Jr., Beaudoin, J.A., Cheng, K.C., Comer, E., Dandapani, S., Dick, J., Duvall, J.R., et al. (2012). Diversity-Oriented Synthesis Yields a Novel Lead for the Treatment of Malaria. ACS Med Chem Lett 3, 112-117.
41. Hughes, T.R., Marton, M.J., Jones, A.R., Roberts, C.J., Stoughton, R., Armour, C.D., Bennett, H.A., Coffey, E., Dai, H., He, Y.D., et al. (2000). Functional discovery via a compendium of expression profiles. Cell 102, 109-126.
42. Israelsen, W.J., Dayton, T.L., Davidson, S.M., Fiske, B.P., Hosios, A.M., Bellinger, G., Li, J., Yu, Y., Sasaki, M., Horner, J.W., et al. (2013). PKM2 isoform-specific deletion reveals a differential requirement for pyruvate kinase in tumor cells. Cell 155, 397-409.
43. Jo, E., Bhhatarai, B., Repetto, E., Guerrero, M., Riley, S., Brown, S.J., Kohno, Y., Roberts, E., Schürer, S.C., and Rosen, H. (2012). Novel selective allosteric and bitopic ligands for the S1P(3) receptor. ACS Chem. Biol. 7, 1975-1983.
44. Jonsson, T., Atwal, J.K., Steinberg, S., Snaedal, J., Jonsson, P.V., Bjornsson, S., Stefansson, H., Sulem, P., Gudbjartsson, D., Maloney, J., et al. (2012). A mutation in APP protects against Alzheimer's disease and age-related cognitive decline. Nature 488, 96-99.
45. Kamenecka, T.M., Busby, S.A., Kumar, N., Choi, J.H., Banks, A.S., Vidovic, D., Cameron, M.D., Schurer, S.C., Mercer, B.A., Hodder, P., et al. (2010). Potent Anti-Diabetic Actions of a Novel Non-Agonist PPARgamma Ligand that Blocks Cdk5 (Bethesda, MD: Mediated Phosphorylation. In Probe Reports from the NIH Molecular Libraries Program).
46. Knuckley, B., Jones, J.E., Bachovchin, D.A., Slack, J., Causey, C.P., Brown, S.J., Rosen, H., Cravatt, B.F., and Thompson, P.R. (2010). A fluopol-ABPP HTS assay to identify PAD inhibitors. Chem. Commun. (Camb.) 46, 7175-7177.
47. Kung, C., Hixon, J., Choe, S., Marks, K., Gross, S., Murphy, E., DeLaBarre, B., Cianchetta, G., Sethumadhavan, S., Wang, X., et al. (2012). Small molecule activation of PKM2 in cancer cells induces serine auxotrophy. Chem. Biol. 19, 1187-1198.
48. Lamb, J., Crawford, E.D., Peck, D., Modell, J.W., Blat, I.C., Wrobel, M.J., Lerner, J., Brunet, J.P., Subramanian, A., Ross, K.N., et al. (2006). The Connectivity Map: using gene-expression signatures to connect small molecules, genes, and disease. Science 313, 1929-1935.
49. Larsen, S.D., Wilson, M.W., Abe, A., Shu, L., George, C.H., Kirchhoff, P., Showalter, H.D., Xiang, J., Keep, R.F., and Shayman, J.A. (2012). Property-based design of a glucosylceramide synthase inhibitor that reduces glucosylceramide in the brain. J. Lipid Res. 53, 282-291.
50. Le, U., Melancon, B.J., Bridges, T.M., Vinson, P.N., Utley, T.J., Lamsal, A., Rodriguez, A.L., Venable, D., Sheffler, D.J., Jones, C.K., et al. (2013). Discovery of a selective M4 positive allosteric modulator based on the 3-amino-thieno[2,3-b]pyridine-2-carboxamide scaffold: development of ML253, a potent and brain penetrant compound that is active in a preclinical model of schizophrenia. Bioorg. Med. Chem. Lett. 23, 346-350.
51. Loo, L.H., Wu, L.F., and Altschuler, S.J. (2007). Image-based multivariate profiling of drug responses from single cells. Nat. Methods 4, 445-453.
52. Lowe, J.T., Lee, M.D., 4th, Akella, L.B., Davoine, E., Donckele, E.J., Durak, L., Duvall, J.R., Gerard, B., Holson, E.B., Joliton, A., et al. (2012). Synthesis and profiling of a diverse collection of azetidine-based scaffolds for the development of CNS-focused lead-like libraries. J. Org. Chem. 77, 7187-7211.
53. Lukens, A.K., Heidebrecht, R.W., Jr., Mulrooney, C., Beaudoin, J.A., Comer, E., Duvall, J.R., Fitzgerald, M.E., Masi, D., Galinsky, K., Scherer, C.A., et al. (2015). Diversity-Oriented Synthesis Probe Targets Plasmodium falciparum Cytochrome b Ubiquinone Reduction Site and Synergizes With Oxidation Site Inhibitors. J. Infect. Dis. 211, 1097-1103.
54. Lunt, S.Y., Muralidhar, V., Hosios, A.M., Israelsen, W.J., Gui, D.Y., Newhouse, L., Ogrodzinski, M., Hecht, V., Xu, K., Acevedo, P.N., et al. (2015). Pyruvate kinase isoform expression alters nucleotide synthesis to impact cell proliferation. Mol. Cell 57, 95-107.
55. Mahley, R.W., and Huang, Y. (2012). Apolipoprotein e sets the stage: response to injury triggers neuropathology. Neuron 76, 871-885.
56. Mandala, S., Hajdu, R., Bergstrom, J., Quackenbush, E., Xie, J., Milligan, J., Thornton, R., Shei, G.J., Card, D., Keohane, C., et al. (2002). Alteration of lymphocyte trafficking by sphingosine-1-phosphate receptor agonists. Science 296, 346-349.
57. Marcaurelle, L.A., Comer, E., Dandapani, S., Duvall, J.R., Gerard, B., Kesavan, S., Lee, M.D., 4th, Liu, H., Lowe, J.T., Marie, J.C., et al. (2010). An aldol-based build/couple/pair strategy for the synthesis of medium- and large-sized rings: discovery of macrocyclic histone deacetylase inhibitors. J. Am. Chem. Soc. 132, 16962-16976.
58. Marciano, D.P., Chang, M.R., Corzo, C.A., Goswami, D., Lam, V.Q., Pascal, B.D., and Griffin, P.R. (2014a). The therapeutic potential of nuclear receptor modulators for treatment of metabolic disorders: PPARg, RORs, and Reverbs. Cell Metab. 19, 193-208.
59. Marciano, D.P., Dharmarajan, V., and Griffin, P.R. (2014b). HDX-MS guided drug discovery: small molecules and biopharmaceuticals. Curr. Opin. Struct. Biol. 28, 105-111.
60. Nesto, R.W., Bell, D., Bonow, R.O., Fonseca, V., Grundy, S.M., Horton, E.S., Le Winter, M., Porte, D., Semenkovich, C.F., Smith, S., et al.; American Heart Association; American Diabetes Association (2003). Thiazolidinedione use, fluid retention, and congestive heart failure: a consensus statement from the American Heart Association and American Diabetes Association. October 7, 2003. Circulation 108, 2941-2948.
61. Niswender, C.M., Rodriguez, A.L., Sheffler, D.J., Utley, T.J., Vinson, P.N., Dawson, E.S., Jones, C.K., Wood, M.R., Daniels, J.S., Conn, P.J., Engers, J.L., Le, U.M., Melancon, B.J., Hopkins, C.R., and Lindsley, C.W. (2010). Extended Probe Characterization: Development of an M4 PAM with Improved Activity and Brain Exposure, while Avoiding Species Bias. In Probe Reports from the NIH Molecular Libraries Program (National Center for Biotechnology Information).
62. Nomura, D.K., Dix, M.M., and Cravatt, B.F. (2010). Activity-based protein profiling for biochemical pathway discovery in cancer. Nat. Rev. Cancer 10, 630-638.
63. Oldstone, M., Hodder, P., Crisp, M., Roberts, E., Guerrero, M., Urbano, M., Velaparthi, S., Zhao, J., Rosen, H., Schaeffer, M.T., et al. (2010). Probe Development Efforts to Identify Novel Antagonists of the Sphingosine 1-phosphate Receptor 4 (S1P4). In Probe Reports from the NIH Molecular Libraries Program (National Center for Biotechnology Information).
64. Oprea, T.I., Bologa, C.G., Boyer, S., Curpan, R.F., Glen, R.C., Hopkins, A.L., Lipinski, C.A., Marshall, G.R., Martin, Y.C., Ostopovici-Halip, L., et al. (2009). A crowdsourcing evaluation of the NIH chemical probes. Nat. Chem. Biol. 5, 441-447.
65. Ortolano, S., Viéitez, I., Navarro, C., and Spuch, C. (2014). Treatment of lysosomal storage diseases: recent patents and future strategies. Recent Pat Endocr Metab Immune Drug Discov 8, 9-25.
66. Orvisky, E., Park, J.K., LaMarca, M.E., Ginns, E.I., Martin, B.M., Tayebi, N., and Sidransky, E. (2002). Glucosylsphingosine accumulation in tissues from patients with Gaucher disease: correlation with phenotype and genotype. Mol. Genet. Metab. 76, 262-270.
67. Panicker, L.M., Miller, D., Park, T.S., Patel, B., Azevedo, J.L., Awad, O., Masood, M.A., Veenstra, T.D., Goldin, E., Stubblefield, B.K., et al. (2012). Induced pluripotent stem cell model recapitulates pathologic hallmarks of Gaucher disease. Proc. Natl. Acad. Sci. USA 109, 18054-18059.
68. Patnaik, S., Zheng, W., Choi, J.H., Motabar, O., Southall, N., Westbroek, W., Lea, W.A., Velayati, A., Goldin, E., Sidransky, E., et al. (2012). Discovery, structure-activity relationship, and biological evaluation of noninhibitory small molecule chaperones of glucocerebrosidase. J. Med. Chem. 55, 5734-5748.
69. Petrone, P.M., Simms, B., Nigsch, F., Lounkine, E., Kutchukian, P., Cornett, A., Deng, Z., Davies, J.W., Jenkins, J.L., and Glick, M. (2012). Rethinking molecular similarity: comparing compounds on the basis of biological activity. ACS Chem. Biol. 7, 1399-1409.
70. Plenge, R.M., Scolnick, E.M., and Altshuler, D. (2013). Validating therapeutic targets through human genetics. Nat. Rev. Drug Discov. 12, 581-594.
71. Reed, J.C., White, E.L., Aubé, J., Lindsley, C., Li, M., Sklar, L., and Schreiber, S. (2012). The NIH's role in accelerating translational sciences. Nat. Biotechnol. 30, 16-19.
72. Reid, P.R., Bridges, T.M., Sheffler, D.J., Cho, H.P., Lewis, L.M., Days, E., Daniels, J.S., Jones, C.K., Niswender, C.M., Weaver, C.D., et al. (2011). Discovery and optimization of a novel, selective and brain penetrant M1 positive allosteric modulator (PAM): the development of ML169, an MLPCN probe. Bioorg. Med. Chem. Lett. 21, 2697-2701.
73. Rogers, S., Patnaik, S., Schoenen, F., Zheng, W., Choi, J., Motabar, O., Southall, N., Westbroek, W., Goldin, E., Sidransky, E., et al. (2010). Discovery, SAR, and Biological Evaluation of Non-inhibitory Chaperones of Glucocerebrosidase. In Probe Reports from the NIH Molecular Libraries Program (National Center for Biotechnology Information).
74. Rosen, H., Gonzalez-Cabrera, P., Marsolais, D., Cahalan, S., Don, A.S., and Sanna, M.G. (2008). Modulating tone: the overture of S1P receptor immunotherapeutics. Immunol. Rev. 223, 221-235.
75. Rosen, H., Stevens, R.C., Hanson, M., Roberts, E., and Oldstone, M.B. (2013). Sphingosine-1-phosphate and its receptors: structure, signaling, and influence. Annu. Rev. Biochem. 82, 637-662.
76. Sanna, M.G., Wang, S.K., Gonzalez-Cabrera, P.J., Don, A., Marsolais, D., Matheu, M.P., Wei, S.H., Parker, I., Jo, E., Cheng, W.C., et al. (2006). Enhancement of capillary leakage and restoration of lymphocyte egress by a chiral S1P1 antagonist in vivo. Nat. Chem. Biol. 2, 434-441.
77. Satsu, H., Schaeffer, M.T., Guerrero, M., Saldana, A., Eberhart, C., Hodder, P., Cayanan, C., Schürer, S., Bhhatarai, B., Roberts, E., et al. (2013). A sphingosine 1-phosphate receptor 2 selective allosteric agonist. Bioorg. Med. Chem. 21, 5373-5382.
78. Simon, G.M., Niphakis, M.J., and Cravatt, B.F. (2013). Determining target engagement in living systems. Nat. Chem. Biol. 9, 200-205.
79. Staels, B. (2005). Fluid retention mediated by renal PPARgamma. Cell Metab. 2, 77-78.
80. Suzuki, Y. (2013). Chaperone therapy update: Fabry disease, GM1-gangliosidosis and Gaucher disease. Brain Dev. 35, 515-523.
81. Tarr, J.C., Turlington, M.L., Reid, P.R., Utley, T.J., Sheffler, D.J., Cho, H.P., Klar, R., Pancani, T., Klein, M.T., Bridges, T.M., et al. (2012). Targeting selective activation of M(1) for the treatment of Alzheimer's disease: further chemical optimization and pharmacological characterization of the M(1) positive allosteric modulator ML169. ACS Chem. Neurosci. 3, 884-895.
82. Teijaro, J.R., Walsh, K.B., Cahalan, S., Fremgen, D.M., Roberts, E., Scott, F., Martinborough, E., Peach, R., Oldstone, M.B., and Rosen, H. (2011). Endothelial cells are central orchestrators of cytokine amplification during influenza virus infection. Cell 146, 980-991.
83. Thiel, P., Kaiser, M., and Ottmann, C. (2012). Small-molecule stabilization of protein-protein interactions: an underestimated concept in drug discovery? Angew. Chem. Int. Ed. Engl. 51, 2012-2018.
84. Tsuboi, K., Bachovchin, D.A., Speers, A.E., Spicer, T.P., Fernandez-Vega, V., Hodder, P., Rosen, H., and Cravatt, B.F. (2011). Potent and selective inhibitors of glutathione S-transferase omega 1 that impair cancer drug resistance. J. Am. Chem. Soc. 133, 16605-16616.
85. Urbano, M., Guerrero, M., Rosen, H., and Roberts, E. (2013). Modulators of the Sphingosine 1-phosphate receptor 1. Bioorg. Med. Chem. Lett. 23, 6377-6389.
86. Urbano, M., Guerrero, M., Velaparthi, S., Crisp, M., Chase, P., Hodder, P., Schaeffer, M.T., Brown, S., Rosen, H., and Roberts, E. (2011a). Discovery, synthesis and SAR analysis of novel selective small molecule S1P4-R agonists based on a (2Z,5Z)-5-((pyrrol-3-yl)methylene)-3-alkyl-2-(alkylimino)thiazolidin-4-one chemotype. Bioorg. Med. Chem. Lett. 21, 6739-6745.
87. Urbano, M., Guerrero, M., Zhao, J., Velaparthi, S., Schaeffer, M.T., Brown, S., Rosen, H., and Roberts, E. (2011b). SAR analysis of innovative selective small molecule antagonists of sphingosine-1-phosphate 4 (S1P4) receptor. Bioorg. Med. Chem. Lett. 21, 5470-5474.
88. Walsh, K.B., Teijaro, J.R., Rosen, H., and Oldstone, M.B. (2011). Quelling the storm: utilization of sphingosine-1-phosphate receptor signaling to ameliorate influenza virus-induced cytokine storm. Immunol. Res. 51, 15-25.
89. Wawer, M.J., Jaramillo, D.E., Dancík, V., Fass, D.M., Haggarty, S.J., Shamji, A.F., Wagner, B.K., Schreiber, S.L., and Clemons, P.A. (2014a). Automated structure-activity relationship mining: connecting chemical structure to biological profiles. J. Biomol. Screen. 19, 738-748.
90. Wawer, M.J., Li, K., Gustafsdottir, S.M., Ljosa, V., Bodycombe, N.E., Marton, M.A., Sokolnicki, K.L., Bray, M.A., Kemp, M.M., Winchester, E., et al. (2014b). Toward performance-diverse small-molecule libraries for cell-based phenotypic screening using multiplexed high-dimensional profiling. Proc. Natl. Acad. Sci. USA 111, 10911-10916.
91. Weinstein, J.N., Myers, T.G., O'Connor, P.M., Friend, S.H., Fornace, A.J., Jr., Kohn, K.W., Fojo, T., Bates, S.E., Rubinstein, L.V., Anderson, N.L., et al. (1997). An information-intensive approach to the molecular pharmacology of cancer. Science 275, 343-349.
92. Weiwer, M., Mulrooney, C., Massi, D., Heidebrecht, R., Wiegand, R., Lukens, A.K., Dick, J., Wirth, D., Ekland, E., Cheng, C.C., et al. (2010). ML238: An Antimalarial Small Molecule of a Unique Structural Class. In Probe Reports from the NIH Molecular Libraries Program (National Center for Biotechnology Information).
93. Wenthur, C.J., Gentry, P.R., Mathews, T.P., and Lindsley, C.W. (2014). Drugs for allosteric sites on receptors. Annu. Rev. Pharmacol. Toxicol. 54, 165-184.
94. Workman, P., and Collins, I. (2010). Probing the probes: fitness factors for small molecule tools. Chem. Biol. 17, 561-577.
95. Young, D.W., Bender, A., Hoyt, J., McWhinnie, E., Chirn, G.W., Tao, C.Y., Tallarico, J.A., Labow, M., Jenkins, J.L., Mitchison, T.J., and Feng, Y. (2008). Integrating high-content screening and ligand-target prediction to identify mechanism of action. Nat. Chem. Biol. 4, 59-68.
96. Yu, J.G., Javorschi, S., Hevener, A.L., Kruszynska, Y.T., Norman, R.A., Sinha, M., and Olefsky, J.M. (2002). The effect of thiazolidinediones on plasma adiponectin levels in normal, obese, and type 2 diabetic subjects. Diabetes 51, 2968-2974.
97. Zanella, A., Fermo, E., Bianchi, P., Chiarelli, L.R., and Valentini, G. (2007). Pyruvate kinase deficiency: the genotype-phenotype association. Blood Rev. 21, 217-231.
98. Zuhl, A.M., Mohr, J.T., Bachovchin, D.A., Niessen, S., Hsu, K.L., Berlin, J.M., Dochnahl, M., López-Alberca, M.P., Fu, G.C., and Cravatt, B.F. (2012). Competitive activity-based protein profiling identifies aza-b-lactams as a versatile chemotype for serine hydrolase inhibition. J. Am. Chem. Soc. 134, 5068-5071.