Biology-oriented synthesis of a natural-product inspired oxepane collection yields a small-molecule activator of the Wnt-pathway

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

Volumn 108, Issue 17, 2011, Pages 6805-6810

  Basua, Sudipta ^a,b,c   Ellinger, Bernhard ^a,b   Rizzo, Stefano ^a   Deraeve, Céline ^a,d   Schürmann, Markus ^b   Preutb, Hans ^b   Arndt, Hans Dieter ^a,b   Waldmann, Herbert ^a,b  

^a MAX PLANCK INSTITUTE OF MOLECULAR PHYSIOLOGY   (Germany)

^b TU DORTMUND UNIVERSITY   (Germany)

^c BRIGHAM AND WOMEN S HOSPITAL   (United States)

^d LCC LABORATOIRE DE CHIMIE DE COORDINATION   (France)

Author keywords

Chemical biology; Compound libraries

Indexed keywords

HELIANNUOL B; HELIANNUOL C; NATURAL PRODUCT; OXEPANE DERIVATIVE; POLYMER; PROTEIN VANGL1; REAGENT; RECEPTOR PROTEIN; SCAVENGER; SODWANONE S; UNCLASSIFIED DRUG; WNT PROTEIN; WNT3A PROTEIN; ZOAPATANOL;

ARTICLE; BIOLOGICAL ACTIVITY; CHEMICAL STRUCTURE; CONTROLLED STUDY; HUMAN; HUMAN CELL; PRIORITY JOURNAL; PROTEOMICS; RING CLOSING METATHESIS; SIGNAL TRANSDUCTION; STRUCTURE ACTIVITY RELATION; SYNTHETIC BIOLOGY;

CARRIER PROTEINS; HEK293 CELLS; HELA CELLS; HEP G2 CELLS; HETEROCYCLIC COMPOUNDS; HUMANS; SIGNAL TRANSDUCTION; WNT PROTEINS;

EID: 79955568244     PISSN: 00278424     EISSN: 10916490     Source Type: Journal    
DOI: 10.1073/pnas.1015269108     Document Type: Article

References (42)

1. Breinbauer R, Vetter IR, Waldmann H (2002) From protein domains to drug candidates- natural products as guiding principles in the design and synthesis of compound libraries. Angewandte Chemie International Edition 41:2878-2890. (Pubitemid 34966550)
2. Koch MA, et al. (2004) Compound library development guided by protein structure similarity clustering and natural product structure. Proc Natl Acad Sci USA 101:16721-16726. (Pubitemid 39601305)
3. Koch MA, et al. (2005) Charting biologically relevant chemical space: a structural classification of natural prducts (SCONP). Proc Natl Acad Sci USA 102:17272-17277. (Pubitemid 41740856)
4. Nören-Müller A, et al. (2006) Discovery of protein phosphatase inhibitor classes by biology-oriented synthesis. Proc Natl Acad Sci USA 103:10606-10611. (Pubitemid 44078024)
5. Bon RS, Waldmann H (2010) Bioactivity-guided navigation of chemical space. Acc Chem Res 43:1103-1114.
6. Hinterding K, Alonso-Díaz D, Waldmann H (1998) Organic synthesis and biological signal transduction. Angewandte Chemie International Edition 37:688-749. (Pubitemid 28214071)
7. Coombs GS, Covey TM, Virshup DM (2008) Wnt signaling, disease and translational medicine. Curr Drug Targets 9:513-531.
8. Green JL, Inoue T, Sternberg PW (2008) Opposing Wnt pathways orient cell polarity during organogenesis. Cell 134:646-656.
9. Tada M, KaiM(2009) Noncanonical Wnt/PCP signaling during vertebrate gastrulation. Zebrafish 6:29-40.
10. Ito M, et al. (2007) Wnt-dependent de novo hair follicle regeneration in adult mouse skin after wounding. Nature 447:316-320. (Pubitemid 46788832)
11. Lepourcelet M, et al. (2004) Small-molecule antagonists of the oncogenic Tcf/betacatenin protein complex. Cancer Cell 5:91-102. (Pubitemid 38121599)
12. Chung N, et al. (2010) A 1,536-well ultra-high-throughput siRNA screen to identify regulators of the Wnt/beta-catenin pathway. Assay Drug Dev Technol 8:286-294.
13. Emami KH, et al. (2004) A small molecule inhibitor of the beta-catenin/CREB binding protein transcription. Proc Natl Acad Sci USA 101:12682-12687. (Pubitemid 39122083)
14. Chen B, et al. (2009) Development of small molecules targeting the Wnt pathway for the treatment of colon cancer: a high-throughput screening approach. Nat Chem Biol 2:100-107.
15. Kochegarov A (2009) Small molecules for stem cells. Expert Opin Ther Pat 19:275-281.
16. Osakada F, et al. (2009) In vitro differentiation of retinal cells from human pluripotent stem cells by small-molecule induction. J Cell Sci 122:3169-3179.
17. Reya T, Clevers H (2005) Wnt signaling in stem cells and cancer. Nature 434:843-850. (Pubitemid 40558990)
18. Zhang DL, et al. (2009) Effect of Wnt signaling pathway on wound healing. Biochem Biophys Res Commun 378:149-151.
19. Fathke C, et al. (2006) Wnt signaling induces epithelial differentiation during cutaneous wound healing. BMC Cell Biol 7:4-12.
20. Silkstone D, Hong H, Alman BA (2008) Beta-catenin in the race to fracture repair: in it to Wnt. Nat Clin Pract Rheum 4:413-419.
21. Coghlan MP, et al. (2000) Selective small molecule inhibitors of glycogen synthase kinase- 3 modulate glycogen metabolism and gene transcription. Chem Biol 7:793-803.
22. Park EJ, et al. (2009) Novel small molecule activators of beta-catenin-mediated signaling pathway: structure-activity relationships of indirubins. Bioorg Med Chem Lett 19:2282-2284.
23. Zhang Q, et al. (2007) Small-molecule synergist of the Wnt/beta-catenin signaling pathway. Proc Natl Acad Sci USA 104:7444-7448. (Pubitemid 47185925)
24. Ley SV, Baxendale IR (2002) New tools and concepts for modern organic synthesis. Nat Rev Drug Discov 1:573-586 and references therein.
25. Macias FA, Molinillo JMG, Varela RM, Torres A, Fronczek FR (1994) Structural elucidation and chemistry of a novel family of bioactive sesquiterpenes: heliannuols. J Org Chem 59:8261-8266.
26. Funel-Le Bon C, Berrue F, Thomas OP, Reyes F, Amade P (2005) Sodwanone S, a triterpene from the marine sponge. Journal of Natural Products 68:1284-1287.
27. Kanojia RM, et al. (1985) Synthesis and antifertility activity of zoapatanol analogs. J Med Chem 28:796-803. (Pubitemid 15026123)
28. Cantrell VA, Jessen JR (2010) The planar cell polarity protein van Gogh-Like 2 regulates tumor cell migration and matrix metalloproteinase- dependent invasion. Cancer Lett 287:54-61.
29. Hoberg OJ (1998) Synthesis of seven-membered oxacycles. Tetrahedron 54:12631-12670.
30. Crimmins MT, Choy AL (1999) An asymmetric aldol-ring-closing metathesis strategy for the enantioselective construction of oxygen heterocycles: an efficient approach to the enantioselective synthesis of (+)-laurencin. J Am Chem Soc 121:5653-5660.
31. Brown HC, Jadhav PK (1983) Asymmetric carbon-carbon bond formation via betaallyldiisopinocampheylborane. simple synthesis of secondary homoallylic alcohols with excellent enantiomeric purity. J Am Chem Soc 105:2092-2093.
32. Westhus M, Gonthier E, Brohm D, Breinbauer R (2004) An efficient and inexpensive scavenger resin for grubbs' catalyst. Tetrahedron Lett 45:3141-3142. (Pubitemid 38373747)
33. Park S, et al. (2006) Hexachlorophene inhibits Wnt/beta-catenin pathway by promoting Siah-mediated beta-catenin degradation. Mol Pharmacol 70:960-966. (Pubitemid 44268452)
34. Meijer L, et al. (2003) GSK-3-selective inhibitors derived from Tyrian purple indirubins. Chem Biol 10:1255-1266. (Pubitemid 38050973)
35. Davidson G, et al. (2009) Cell cycle control of Wnt receptor activation. Dev Cell 17:788-799.
36. Gessert S, Maurus D, Rossner A, KuhlM(2007) Pescadillo is required for Xenopus laevis eye development and neural crest migration. Dev Biol 310:99-112. (Pubitemid 47445492)
37. Torban E, et al. (2008) Genetic interaction between members of the Vangl family causes neural tube defects in mice. Proc Natl Acad Sci USA 105:3449-3454. (Pubitemid 351723573)
38. Bastock R, Strutt H, Strutt D (2003) Strabismus is asymmetrically localized and binds to Prickle and Dishevelled during Drosophila planar polarity patterning. Development 130:3007-3014. (Pubitemid 36857247)
39. Katoh M (2002) Strabismus (STB)/Vang-like gene family. Int J Mol Med 10:11-15.
40. ParkM, Moon RT (2002) The planar cell-polarity gene stbm regulates cell behavior and cell fate in vertebrate embryos. Nat Cell Biol 4:20-25.
41. Axelrod JD (2002) Strabismus comes into focus. Nat Cell Biol 4:E6-8.
42. Zhang JH, Chung TD, Oldenburg KR (1999) A simple statistical parameter for use in evaluation and validation of high throughput screening assays. J Biomol Screen 4:67-73. (Pubitemid 29278954)