Organic synthesis toward small-molecule probes and drugs

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

Volumn 108, Issue 17, 2011, Pages 6699-6702

  Schreiber, Stuart L ^a,b  

^a BROAD INSTITUTE OF MIT AND HARVARD   (United States)

^b HARVARD UNIVERSITY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ANTIMALARIAL AGENT; ERIBULIN; NATURAL PRODUCT;

BINDING AFFINITY; DRUG SYNTHESIS; FEMALE; HUMAN; MACROMOLECULE; MOLECULAR LIBRARY; MOLECULAR PROBE; MOLECULAR THERAPY; NONHUMAN; ORGANIC CHEMISTRY; ORGANIC SYNTHESIS; PRIORITY JOURNAL; REVIEW; SIGNAL TRANSDUCTION; STRUCTURE ACTIVITY RELATION; SYNTHESIS;

DRUG DESIGN; HUMANS; MOLECULAR PROBES;

EID: 79955563790     PISSN: 00278424     EISSN: 10916490     Source Type: Journal    
DOI: 10.1073/pnas.1103205108     Document Type: Review

References (31)

1. Zlotkin E, Shulov AS (1969) Recent studies on the mode of action of scorpion neurotoxins. A review. Toxicon 7: 217-221.
2. Carlsson A (1990) Early psychopharmacology and the rise of modern brain research. J Psychopharmacol 4: 120-126.
3. Kresge N, Simoni RD, Hill RL (2010) Yasutomi Nishizuka's discovery of protein kinase C. J Biol Chem 285:e15.
4. Blumberg PM (1988) Protein kinase C as the receptor for the phorbol ester tumor promoters: Sixth Rhoads memorial award lecture. Cancer Res 48:1-8.
5. Borisy GG, Taylor EW (1967) The mechanism of action of colchicine. Colchicine binding to sea urchin eggs and the mitotic apparatus. J Cell Biol 34:535-548.
6. Peterson JR, Mitchison TJ (2002) Small molecules, big impact: A history of chemical inhibitors and the cytoskeleton. Chem Biol 9:1275-1285. (Pubitemid 36010683)
7. Raju TN (2000) The Nobel chronicles. 1988: James Whyte Black, (b 1924), Gertrude Elion (1918-99), and George H Hitchings (1905-98). Lancet 355:1022.
8. Schreiber SL, Kapoor T, Wess G (2007) Chemical Biology. From Small Molecules to Systems Biology and Drug Design (Wiley-VCH, New York), 1st Ed.
9. Belshaw PJ, Schoepfer J, Liu K, Morrison K, Schreiber SL (1995) Rational design of orthogonal receptor-ligand combinations. Angew Chem Int Ed Engl 34:2129-2132.
10. Belshaw PJ, Schreiber SL (1997) Cell-specific calcineurin inhibition by a modified cyclosporin. J Am Chem Soc 119:1805-1806. (Pubitemid 27145535)
11. Knight ZA, Shokat KM (2007) Chemical genetics: Where genetics and pharmacology meet. Cell 128:425-430. (Pubitemid 46198904)
12. Brown EJ, et al. (1995) Control of p70 s6 kinase by kinase activity of FRAP in vivo. Nature 377:441-446.
13. Schreiber SL (1998) Chemical genetics resulting from a passion for synthetic organic chemistry. Bioorg Med Chem 6:1127-1152.
14. Schreiber SL (2003) The small-molecule approach to biology: Chemical genetics and diversity-oriented organic synthesis make possible the systematic exploration of biology. Chem Eng News 81:51-61.
15. Stanton BZ, et al. (2009) A small molecule that binds Hedgehog and blocks its signaling in human cells. Nat Chem Biol 5:154-156.
16. Koehler AN (2010) A complex task? Direct modulation of transcription factors with small molecules. Curr Opin Chem Biol 14:331-340.
17. Arkin MR, Wells JA (2004) Small-molecule inhibitors of protein-protein interactions: Progressing towards the dream. Nat Rev Drug Discov 3:301-317. (Pubitemid 38499758)
18. Berg T (2008) Small-molecule inhibitors of protein-protein interactions. Curr Opin Drug Discov Dev 11:666-674.
19. Sarkar S, et al. (2007) Small molecules enhance autophagy and reduce toxicity in Huntington's disease models. Nat Chem Biol 3:331-338. (Pubitemid 46789270)
20. Fomina-Yadlin D, et al. (2010) Small-molecule inducers of insulin expression in pancreatic alpha-cells. Proc Natl Acad Sci USA 107:15099-15104.
21. Schreiber SL (2009) The gap between scientists' aspiration and society's expectations. ChemBioChem 10:26-29.
22. Sharma SV, Haber DA, Settleman J (2010) Cell linebased platforms to evaluate the therapeutic efficacy of candidate anticancer agents. Nat Rev Cancer 10:241-253.
23. Schreiber SL, et al.; Cancer Target Discovery and Development Network (2010) Towards patientbased cancer therapeutics. Nat Biotechnol 28:904-906.
24. Shaw SY, et al. (2011) Disease allele-dependent small-molecule sensitivities in blood cells from monogenic diabetes. Proc Natl Acad Sci USA 108: 492-497.
25. Ledford H (2010) Complex synthesis yields breastcancer therapy. Nature 468:608-609.
26. Yu MJ, Kishi Y, Littlefield BA (2005) in Anticancer Agents from Natural Products, eds Cragg GM, Newman DJ, Kingston DGI (Boca Raton, FL), pp 241-266.
27. Rottmann M, et al. (2010) Spiroindolones, a potent compound class for the treatment of malaria. Science 329:1175-1180.
28. Gamo F-J, et al. (2010) Thousands of chemical starting points for antimalarial lead identification. Nature 465: 305-310.
29. Clemons PA, et al. (2010) Small molecules of different synthetic and natural origins have distinct distributions of structural complexity that correlate with proteinbinding profiles. Proc Natl Acad Sci USA 107: 18787-18792.
30. Nielsen TE, Schreiber SL (2008) Towards the optimal screening collection: A synthesis strategy. Angew Chem Int Ed Engl 47:48-56.
31. Wadman M (2010) 'Cure acceleration' funds woven into health reform legislation. Nat Med 16:135.