Impact of the smoothened inhibitor, IPI-926, on smoothened ciliary localization and hedgehog pathway activity

PLoS ONE

Volumn 9, Issue 3, 2014, Pages

  Peluso, Marisa O ^a   Campbell, Veronica T ^a   Harari, Joseph A ^a   Tibbitts, Thomas T ^a   Proctor, Jennifer L ^a   Whitebread, Nigel ^a   Conley, James M ^a   White, Kerry F ^a   Kutok, Jeffery L ^a   Read, Margaret A ^a   McGovern, Karen ^a   Faia, Kerrie L ^a  

^a Infinity Pharmaceuticals Inc   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

CYCLOPAMINE; SARIDEGIB; SMOOTHENED PROTEIN; SONIC HEDGEHOG PROTEIN; G PROTEIN COUPLED RECEPTOR; IPI-926; SMO PROTEIN, HUMAN; SMO PROTEIN, MOUSE; VERATRUM ALKALOID;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; CANCER INHIBITION; CELL LINE; CELL SPECIFICITY; CELL STIMULATION; CELLULAR DISTRIBUTION; CONTROLLED STUDY; DRUG BLOOD LEVEL; DRUG POTENCY; EUKARYOTIC FLAGELLUM; IN VITRO STUDY; IN VIVO STUDY; MALE; MOUSE; NONHUMAN; PANCREAS CANCER; PROTEIN LOCALIZATION; SIGNAL TRANSDUCTION; SINGLE DRUG DOSE; TUMOR XENOGRAFT; 3T3 CELL LINE; ANIMAL; DRUG EFFECTS; HUMAN; METABOLISM;

ANIMALS; CELL LINE; CILIA; HEDGEHOG PROTEINS; HUMANS; MICE; NIH 3T3 CELLS; RECEPTORS, G-PROTEIN-COUPLED; SIGNAL TRANSDUCTION; VERATRUM ALKALOIDS;

EID: 84897495675     PISSN: None     EISSN: 19326203     Source Type: Journal    
DOI: 10.1371/journal.pone.0090534     Document Type: Article

References (20)

1. Hahn H, Wicking C, Zaphiropoulous PG, Gailani MR, Shanley S, et al. (1996) Mutations of the human homolog of Drosophila patched in the nevoid basal cell carcinoma syndrome. Cell 85: 841-851. (Pubitemid 26192135)
2. Jiang J, Hui C-C (2008) Hedgehog Signaling in Development and Cancer. Developmental Cell 15: 801-812.
3. Nozawa YI, Lin C, Chuang PT (2013) Hedgehog signaling from the primary cilium to the nucleus: an emerging picture of ciliary localization, trafficking and transduction. Curr Opin Genet Dev.
4. Rohatgi R, Milenković L, Scott MP (2007) Patched1 Regulates Hedgehog Signaling at the Primary Cilium. Science 317: 372-376. (Pubitemid 47106377)
5. Milenkovic L, Scott MP, Rohatgi R (2009) Lateral transport of Smoothened from the plasma membrane to the membrane of the cilium. J Cell Biol 187: 365-374.
6. Rohatgi R, Milenkovic L, Corcoran RB, Scott MP (2009) Hedgehog signal transduction by Smoothened: pharmacologic evidence for a 2-step activation process. Proc Natl Acad Sci USA 106: 3196-3201.
7. Wang Y, Zhou Z, Walsh CT, McMahon AP (2009) Selective translocation of intracellular Smoothened to the primary cilium in response to Hedgehog pathway modulation. Proc Natl Acad Sci USA 106: 2623-2628.
8. Wang Y, Arvanites AC, Davidow L, Blanchard J, Lam K, et al. (2012) Selective identification of hedgehog pathway antagonists by direct analysis of smoothened ciliary translocation. ACS Chem Biol 7: 1040-1048.
9. Tremblay MR, Lescarbeau A, Grogan MJ, Tan E, Lin G, et al. (2009) Discovery of a potent and orally active hedgehog pathway antagonist (IPI-926). J Med Chem 52: 4400-4418.
10. Nakamura T, Aikawa T, Iwamoto-Enomoto M, Iwamoto M, Higuchi Y, et al. (1997) Induction of osteogenic differentiation by hedgehog proteins. Biochem Biophys Res Commun 237: 465-469. (Pubitemid 27406054)
11. van der Horst G, Farih-Sips H, Lowik CW, Karperien M (2003) Hedgehog stimulates only osteoblastic differentiation of undifferentiated KS483 cells. Bone 33: 899-910. (Pubitemid 37543566)
12. Chen JK, Taipale J, Cooper MK, Beachy PA (2002) Inhibition of Hedgehog signaling by direct binding of cyclopamine to Smoothened. Genes Dev 16: 2743-2748. (Pubitemid 35253140)
13. Wilson CW, Chen MH, Chuang PT (2009) Smoothened adopts multiple active and inactive conformations capable of trafficking to the primary cilium. PLoS One 4: e5182.
14. Wang Y, Davidow L, Arvanites AC, Blanchard J, Lam K, et al. (2012) Glucocorticoid compounds modify smoothened localization and hedgehog pathway activity. Chem Biol 19: 972-982.
15. Yauch RL, Gould SE, Scales SJ, Tang T, Tian H, et al. (2008) A paracrine requirement for hedgehog signalling in cancer. Nature 455: 406-410.
16. Wu VM, Chen SC, Arkin MR, Reiter JF (2012) Small molecule inhibitors of Smoothened ciliary localization and ciliogenesis. Proceedings of the National Academy of Sciences 109: 13644-13649.
17. Yauch RL, Dijkgraaf GJ, Alicke B, Januario T, Ahn CP, et al. (2009) Smoothened mutation confers resistance to a Hedgehog pathway inhibitor in medulloblastoma. Science 326: 572-574.
18. Wang C, Wu H, Katritch V, Han GW, Huang X-P, et al. (2013) Structure of the human smoothened receptor bound to an antitumour agent. Nature 497: 338-343.
19. Chen Y, Sasai N, Ma G, Yue T, Jia J, et al. (2011) Sonic Hedgehog dependent phosphorylation by CK1alpha and GRK2 is required for ciliary accumulation and activation of smoothened. PLoS Biol 9: e1001083.
20. Arbiser JL, Raab G, Rohan RM, Paul S, Hirschi K, et al. (1999) Isolation of mouse stromal cells associated with a human tumor using differential diphtheria toxin sensitivity. Am J Pathol 155: 723-729. (Pubitemid 29426818)