Expanding the Range of 'druggable' Targets with Natural Product-based Libraries: an Academic Perspective

Overview

Journal Curr Opin Chem Biol

Publisher Elsevier

Specialty Biochemistry

Date 2010 Mar 6

PMID 20202892

Citations 69

Authors

Renato A Bauer

Jacqueline M Wurst

Derek S Tan

Affiliations

Soon will be listed here.

Abstract

Existing drugs address a relatively narrow range of biological targets. As a result, libraries of drug-like molecules have proven ineffective against a variety of challenging targets, such as protein-protein interactions, nucleic acid complexes, and antibacterial modalities. In contrast, natural products are known to be effective at modulating such targets, and new libraries are being developed based on underrepresented scaffolds and regions of chemical space associated with natural products. This has led to several recent successes in identifying new chemical probes that address these challenging targets.

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References

Peng L, Stanton B, Maloof N, Wang X, Schreiber S . Syntheses of aminoalcohol-derived macrocycles leading to a small-molecule binder to and inhibitor of Sonic Hedgehog. Bioorg Med Chem Lett. 2009; 19(22):6319-25. PMC: 2796117. DOI: 10.1016/j.bmcl.2009.09.089. View

Driggers E, Hale S, Lee J, Terrett N . The exploration of macrocycles for drug discovery--an underexploited structural class. Nat Rev Drug Discov. 2008; 7(7):608-24. DOI: 10.1038/nrd2590. View

Kotake Y, Sagane K, Owa T, Mimori-Kiyosue Y, Shimizu H, Uesugi M . Splicing factor SF3b as a target of the antitumor natural product pladienolide. Nat Chem Biol. 2007; 3(9):570-5. DOI: 10.1038/nchembio.2007.16. View

Newman D, Cragg G, Snader K . Natural products as sources of new drugs over the period 1981-2002. J Nat Prod. 2003; 66(7):1022-37. DOI: 10.1021/np030096l. View

Hert J, Irwin J, Laggner C, Keiser M, Shoichet B . Quantifying biogenic bias in screening libraries. Nat Chem Biol. 2009; 5(7):479-83. PMC: 2783405. DOI: 10.1038/nchembio.180. View

Ng P, Tang Y, Knosp W, Stadler H, Shaw J . Synthesis of diverse lactam carboxamides leading to the discovery of a new transcription-factor inhibitor. Angew Chem Int Ed Engl. 2007; 46(28):5352-5. DOI: 10.1002/anie.200700762. View

Overington J, Al-Lazikani B, Hopkins A . How many drug targets are there?. Nat Rev Drug Discov. 2006; 5(12):993-6. DOI: 10.1038/nrd2199. View

Golas M, Sander B, Will C, Luhrmann R, Stark H . Molecular architecture of the multiprotein splicing factor SF3b. Science. 2003; 300(5621):980-4. DOI: 10.1126/science.1084155. View

Shelat A, Guy R . Scaffold composition and biological relevance of screening libraries. Nat Chem Biol. 2007; 3(8):442-6. DOI: 10.1038/nchembio0807-442. View

10.

Bister B, Bischoff D, Strobele M, Riedlinger J, Reicke A, Wolter F . Abyssomicin C-A polycyclic antibiotic from a marine Verrucosispora strain as an inhibitor of the p-aminobenzoic acid/tetrahydrofolate biosynthesis pathway. Angew Chem Int Ed Engl. 2004; 43(19):2574-6. DOI: 10.1002/anie.200353160. View

11.

Keller S, Schadt H, Ortel I, Sussmuth R . Action of atrop-abyssomicin C as an inhibitor of 4-amino-4-deoxychorismate synthase PabB. Angew Chem Int Ed Engl. 2007; 46(43):8284-6. DOI: 10.1002/anie.200701836. View

12.

Payne D, Gwynn M, Holmes D, Pompliano D . Drugs for bad bugs: confronting the challenges of antibacterial discovery. Nat Rev Drug Discov. 2006; 6(1):29-40. DOI: 10.1038/nrd2201. View

13.

Pommier Y, Marchand C . Interfacial inhibitors of protein-nucleic acid interactions. Curr Med Chem Anticancer Agents. 2005; 5(4):421-9. DOI: 10.2174/1568011054222337. View

14.

Wahl M, Will C, Luhrmann R . The spliceosome: design principles of a dynamic RNP machine. Cell. 2009; 136(4):701-18. DOI: 10.1016/j.cell.2009.02.009. View

15.

Ni Chonghaile T, Letai A . Mimicking the BH3 domain to kill cancer cells. Oncogene. 2009; 27 Suppl 1:S149-57. PMC: 3733265. DOI: 10.1038/onc.2009.52. View

16.

Dobson C . Chemical space and biology. Nature. 2004; 432(7019):824-8. DOI: 10.1038/nature03192. View

17.

Stanton B, Peng L, Maloof N, Nakai K, Wang X, Duffner J . A small molecule that binds Hedgehog and blocks its signaling in human cells. Nat Chem Biol. 2009; 5(3):154-6. PMC: 2770933. DOI: 10.1038/nchembio.142. View

18.

Fischbach M, Walsh C . Antibiotics for emerging pathogens. Science. 2009; 325(5944):1089-93. PMC: 2802854. DOI: 10.1126/science.1176667. View

19.

Rymond B . Targeting the spliceosome. Nat Chem Biol. 2007; 3(9):533-5. DOI: 10.1038/nchembio0907-533. View

20.

Feher M, Schmidt J . Property distributions: differences between drugs, natural products, and molecules from combinatorial chemistry. J Chem Inf Comput Sci. 2003; 43(1):218-27. DOI: 10.1021/ci0200467. View