Chemical methodology as a source of small-molecule checkpoint inhibitors and heat shock protein 70 (Hsp70) modulators

Proceedings of the National Academy of Sciences of the United States of America

Volumn 108, Issue 17, 2011, Pages 6757-6762

  Huryn, Donna M ^a   Brodsky, Jeffrey L ^a   Brummond, Kay M ^a   Chambers, Peter G ^a   Eyer, Benjamin ^a   Ireland, Alex W ^a   Kawasumi, Masaoki ^b   LaPorte, Matthew G ^a   Lloyd, Kayla ^a   Manteau, Baptiste ^a   Nghiem, Paul ^b,c   Quade, Bettina ^a   Seguin, Sandlin P ^a   Wipf, Peter ^a  

^a UNIVERSITY OF PITTSBURGH   (United States)

^b UNIVERSITY OF WASHINGTON   (United States)

^c Fred Hutchinson Cancer Research Center   (United States)

Author keywords

Alpha methylene cyclopentenone; ATPase; Diversity oriented synthesis; Isosteres; UPCMLD

Indexed keywords

ATM PROTEIN; ATR PROTEIN; BINDING PROTEIN; CHAPERONE; DMT 3024; DMT 3132; HEAT SHOCK PROTEIN 70; MAL2 11B; MAL3 101; MARPIN; PROTEIN INHIBITOR; PROTEIN P53; PYRIMIDINONE DERIVATIVE; TETRAZOLE DERIVATIVE; UNCLASSIFIED DRUG;

ANTINEOPLASTIC ACTIVITY; ARTICLE; BIOLOGICAL ACTIVITY; CHEMICAL ANALYSIS; CHEMICAL MODIFICATION; CHEMICAL PROCEDURES; CHEMICAL STRUCTURE; CONTROLLED STUDY; DNA DAMAGE; DRUG RESEARCH; DRUG SCREENING; HUMAN; HUMAN CELL; MALARIA; MODULATION; MOLECULAR LIBRARY; MOLECULAR PROBE; NONHUMAN; POLYOMA VIRUS; PRIORITY JOURNAL; STRUCTURE ACTIVITY RELATION; SYNTHESIS; TRYPANOSOMIASIS; VIRUS REPLICATION;

CELL CYCLE PROTEINS; CELL LINE; DNA-BINDING PROTEINS; DRUG DESIGN; HSP70 HEAT-SHOCK PROTEINS; HUMANS; MOLECULAR PROBES; POLYOMAVIRUS; POLYOMAVIRUS INFECTIONS; PROTEIN-SERINE-THREONINE KINASES; SIGNAL TRANSDUCTION; TUMOR SUPPRESSOR PROTEINS; VIRUS REPLICATION;

POLYOMAVIRUS;

EID: 79955567706     PISSN: 00278424     EISSN: 10916490     Source Type: Journal    
DOI: 10.1073/pnas.1015251108     Document Type: Article

References (38)

1. Center for Chemical Methodologies & Library Development (UPCMLD) , http://ccc.chem.pitt.edu/.
2. Dancik V, Seiler KP, Young DW, Schreiber SL, Clemons PA (2010) Distinct biological network properties between the targets of natural products and disease genes. J Am Chem Soc 132:9259-9261.
3. NCBI Pubchem Structure Search:, http://pubchem.ncbi.nlm.nih.gov/.
4. Fewell SW, et al. (2004) Small molecule modulators of endogenous and co-chaperon-stimulated Hsp70 ATPase activity. J Biol Chem 279:51131-51140.
5. Tan DS (2005) Diversity-oriented synthesis: exploring the intersections between chemistry and biology. Nat Chem Biol 1:74-84.
6. Dandapani S, Marcaurelle LA (2010) Current strategies for diversity-oriented synthesis. Curr Opin Chem Biol 14:362-370.
7. Lipkus AH, et al. (2008) A scaffold analysis of the 24million compounds in the Chemical Abstracts (CAS) database reveals that half of the compounds can be described by a mere 143 molecular frameworks. J Org Chem 73:4443-4451.
8. Brummond KM, Mitasev B (2004) Allenes and transition metals: a diverging approach to heterocycles. Org Lett 6:2245-2248.
9. Brummond KM, Chen D (2005) Microwave-assisted intramolecular [2 + 2] allenic cycloaddition reaction for the rapid assembly of bicyclo[4.2.0]octa-1,6, -dienes and bicyclo[5.2.0]nona-1,7-dienes. Org Lett 7:3473-3475.
10. Brummond KM, Chen H, Mitasev B, Casarez AD (2004) A Rhodium(I)-catalyzed ene-allene carbocyclization strategy for the formation of azepines and oxepines. Org Lett 6:2161-2163.
11. Hann MM, Oprea TI (2004) Pursuing the lead likeness concept in pharmaceutical research. Curr Opin Chem Biol 8:255-263.
12. Werner S, et al. (2006) Solution-phase synthesis of a tricyclic pyrrole-2-carboxamide discovery library applying a Stetter-Paal-Knorr reaction sequence. J Comb Chem 8:368-380.
13. Bizzantz C, Kuhn B, Stahl M (2010) A medicinal chemist's guide to molecular interactions. J Med Chem 53:5061-5084.
14. Zhou BB, Bartek J (2004) Targeting the checkpoint kinases: chemosensitization versus chemoprotection. Nat Rev Cancer 4:216-225.
15. Nghiem P, Park PK, Kim YS, Vaziri C, Schreiber SL (2001) ATR inhibition selectively sensitizes G1 checkpoint-deficient cells to lethal premature chromatin condensation. Proc Natl Acad Sci USA 98:9092-9097.
16. Potashman MH, Duggan ME (2009) Covalent modifiers: an orthogonal approach to drug design. J Med Chem 52:1231-1246.
17. Godl K, et al. (2003) An efficient proteomics method to identify the cellular targets of protein kinase inhibitors. Proc Natl Acad Sci USA 100:15434-15439.
18. Ong SE, et al. (2009) Identifying the proteins to which small-molecule probes and drugs bind in cells. Proc Natl Acad Sci USA 106:4617-4622.
19. Sherman MY, Goldberg AL (2001) Cellular defenses against unfolded proteins: a cell biologist thinks about neurodegenerative diseases. Neuron 29:15-32.
20. Brodsky J, Chiosis G (2006) Hsp70 molecular chaperones: emerging roles in human disease and identification of small molecule modulators. Curr Top Med Chem 6:1215-1225.
21. Didelot C, et al. (2007) Anti-cancer therapeutic approaches based on intracellular and extracellular heat shock proteins. Curr Med Chem 14:2839-2847.
22. Evans CG, Chang L, Gestwicki JE (2010) Heat shock protein 70 (Hsp70) as an emerging drug target. J Med Chem 53:4585-4602.
23. Shonhai A (2010) Plasmodial heat shock proteins: targets for chemotherapy. FEMS Immunol Med Microbiol 58:61-74.
24. Wang YP, et al. (2010) Heat stress cognate 70 host protein as a potential drug target against drug resistance in hepatitis B virus. Antimicrob Agents Chemother 54:2070-2077.
25. Powers MV, et al. (2010) Targeting Hsp70: the second potentially druggable heat shock protein and molecular chaperone? Cell Cycle 9:1542-1550.
26. Patury S, Miytata Y, Gestwicki JE (2009) Pharmacological targeting of the Hsp70 chaperone. Curr Top Med Chem 9:1337-1351 and references cited within.
27. Rodina A, et al. (2007) Selective compounds define Hsp90 as a major inhibitor of apoptosis in small-cell lung cancer. Nat Chem Biol 3:498-507.
28. Rabu C, Wipf P, Brodsky J, High S (2008) A precursor-specific rold for Hsp40/hsc70 during tail-anchored protein integration at the endoplasmic reticulum. J Biol Chem 283:27504-27513.
29. Patham B, et al. (2009) Post-translational import of protein into the endoplasmic reticulum of a trypanosome: an in vitro system for discovery of anti-trypansomal chemical entities. Biochem J 419:507-517.
30. Wright CM, et al. (2008) Pyrimidinone-peptoid hybrid molecules with distinct effects on molecular chaperone function and cell proliferation. Bioorg Med Chem 16:3291-3301.
31. Chiang AN, et al. (2009) Select pyrimidinones inhibit the propagation of the malarial parasite, Plasmodium falciparum. Bioorg Med Chem 17:1527-1533.
32. Wright CM, et al. (2009) Inhibition of simian virus 40 replication by targeting the molecular chaperone function and ATPase activity of T antigen. Virus Res 141:71-80.
33. Jiang M, Abend JR, Johnson SF, Imperiale MJ (2009) The role of polyomaviruses in human disease. Virology 384:266-273.
34. Werner S, Turner DM, Lyon MA, Huryn DM, Wipf P (2006) A focused library of tetrahydropyrimidinone amides via a tandem Biginelli-Ugi multi-component process. Synlett 14:2334-2338.
35. Kampinga HH, Craig EA (2010) The Hsp70 chaperone machinery: J proteins as drivers of functional specificity. Nature Rev Mol Cell Bio 11:579-592.
36. Wisen S, et al. (2010) Binding of a small molecule at a protein-protein interface regulates the chaperone activity of Hsp70-Hsp40. ACS Chem Biol 5:611-622.
37. Reddy AS, Kumar MS, Reddy GR (2000) A convenient method for the preparation of hydroxamic acids. Tetrahedron Lett 41:6285-6288.
38. Amantini D, Beleggia R, Fringuelli F, Pizzo F, Vaccaro L (2004) TBAF-catalyzed synthesis of 5-substituted 1H-tetrazoles under solventless conditions. J Org Chem 69:2896-2898.