NL-103, a novel dual-targeted inhibitor of histone deacetylases and hedgehog pathway, effectively overcomes vismodegib resistance conferred by Smo mutations

Pharmacology Research and Perspectives

Volumn 2, Issue 3, 2014, Pages

  Zhao, Jie ^a   Quan, Haitian ^a   Xie, Chengying ^a   Lou, Liguang ^a  

^a SHANGHAI INSTITUTE OF MATERIA MEDICA   (China)

Author keywords

Drug resistance; hedgehog pathway inhibitor; histone deacetylase inhibitor; NL 103; smoothened mutation

Indexed keywords

HISTONE DEACETYLASE; HISTONE DEACETYLASE INHIBITOR; NL 103; PROTEIN PATCHED 1; SMOOTHENED PROTEIN; SONIC HEDGEHOG PROTEIN; TRANSCRIPTION FACTOR GLI1; TRANSCRIPTION FACTOR GLI2; TRANSCRIPTION FACTOR GLI3; UNCLASSIFIED DRUG; VISMODEGIB; VORINOSTAT;

ANIMAL CELL; ARTICLE; BASAL CELL CARCINOMA; CHEMICAL STRUCTURE; CONTROLLED STUDY; DRUG RESPONSE; ENZYME INHIBITION; ENZYME INHIBITION ASSAY; GENE TRANSLOCATION; GENETIC TRANSFECTION; HEDGEHOG SIGNALING; HEK293T CELL LINE; HUMAN; HUMAN CELL; LUCIFERASE ASSAY; MEDULLOBLASTOMA; NIH 3T3 CELL LINE; NONHUMAN; POINT MUTATION; PRIMARY CILIUM; PRIORITY JOURNAL; PROTEIN EXPRESSION; REAL TIME POLYMERASE CHAIN REACTION; SYNTHESIS;

EID: 84957021931     PISSN: None     EISSN: 20521707     Source Type: Journal    
DOI: 10.1002/prp2.43     Document Type: Article

References (41)

1. Bai CB, Joyner AL (2001). Gli1 can rescue the in vivo function of Gli2. Development 128: 5161–5172.
2. Bai CB, Auerbach W, Lee JS, Stephen D, Joyner AL (2002). Gli2, but not Gli1, is required for initial Shh signaling and ectopic activation of the Shh pathway. Development 129: 4753–4761.
3. Bolden JE, Peart MJ, Johnstone RW (2006). Anticancer activities of histone deacetylase inhibitors. Nat Rev Drug Discovery 5: 769–784.
4. Cai X, Zhai H-X, Wang J, Forrester J, Qu H, Yin L, et al. (2010). Discovery of 7-(4-(3-ethynylphenylamino)-7-methoxyquinazolin-6-yloxy)-N-hydroxyheptanamide (CUDC-101) as a potent multi-acting HDAC, EGFR, and HER2 inhibitor for the treatment of cancer. J Med Chem 53: 2000–2009.
5. Canettieri G, Di Marcotullio L, Greco A, Coni S, Antonucci L, Infante P, et al. (2010). Histone deacetylase and Cullin3–RENKCTD11 ubiquitin ligase interplay regulates Hedgehog signalling through Gli acetylation. Nat Cell Biol 12: 132–142.
6. Chen JK, Taipale J, Cooper MK, Beachy PA (2002a). Inhibition of Hedgehog signaling by direct binding of cyclopamine to Smoothened. Genes Dev 16: 2743–2748.
7. Chen JK, Taipale J, Young KE, Maiti T, Beachy PA (2002b). Small molecule modulation of Smoothened activity. Proc Natl Acad Sci USA 99: 14071–14076.
8. Dijkgraaf GJ, Alicke B, Weinmann L, Januario T, West K, Modrusan Z, et al. (2011). Small molecule inhibition of GDC-0449 refractory smoothened mutants and downstream mechanisms of drug resistance. Cancer Res 71: 435–444.
9. Gailani MR, Ståhle-Bäckdahl M, Leffell DJ, Glyn M, Zaphiropoulos PG, Undén AB, et al. (1996). The role of the human homologue of Drosophila patched in sporadic basal cell carcinomas. Nat Genet 14: 78–81.
10. Gerdes JM, Davis EE, Katsanis N (2009). The vertebrate primary cilium in development, homeostasis, and disease. Cell 137: 32–45.
11. Goetz SC, Anderson KV (2010). The primary cilium: a signalling centre during vertebrate development. Nat Rev Genet 11: 331–344.
12. Goodrich LV, Milenković L, Higgins KM, Scott MP (1997). Altered neural cell fates and medulloblastoma in mouse patched mutants. Science 277: 1109–1113.
13. Grachtchouk M, Mo R, Yu S, Zhang X, Sasaki H, C-c Hui, et al. (2000). Basal cell carcinomas in mice overexpressing Gli2 in skin. Nat Genet 24: 216–217.
14. Hammond JW, Cai D, Verhey KJ (2008). Tubulin modifications and their cellular functions. Curr Opin Cell Biol 20: 71–76.
15. Han Y-G, Kim HJ, Dlugosz AA, Ellison DW, Gilbertson RJ, Alvarez-Buylla A (2009). Dual and opposing roles of primary cilia in medulloblastoma development. Nat Med 15: 1062–1065.
16. Haycraft CJ, Banizs B, Aydin-Son Y, Zhang Q, Michaud EJ, Yoder BK (2005). Gli2 and Gli3 localize to cilia and require the intraflagellar transport protein polaris for processing and function. PLoS Genet 1: e53.
17. Hyman JM, Firestone AJ, Heine VM, Zhao Y, Ocasio CA, Han K, et al. (2009). Small-molecule inhibitors reveal multiple strategies for Hedgehog pathway blockade. Proc Natl Acad Sci USA 106: 14132–14137.
18. Ingham PW, McMahon AP (2001). Hedgehog signaling in animal development: paradigms and principles. Genes Dev 15: 3059–3087.
19. Jacob J, Briscoe J (2003). Gli proteins and the control of spinal-cord patterning. EMBO Rep 4: 761–765.
20. Kim J, Kato M, Beachy PA (2009). Gli2 trafficking links Hedgehog-dependent activation of Smoothened in the primary cilium to transcriptional activation in the nucleus. Proc Natl Acad Sci USA 106: 21666–21671.
21. Kovacs JJ, Whalen EJ, Liu R, Xiao K, Kim J, Chen M, et al. (2008). {beta}-Arrestin-mediated localization of smoothened to the primary cilium. Science Signalling 320: 1777.
22. Lane AA, Chabner BA (2009). Histone deacetylase inhibitors in cancer therapy. J Clin Oncol 27: 5459–5468.
23. Lee Y, Kawagoe R, Sasai K, Li Y, Russell H, Curran T, et al. (2007). Loss of suppressor-of-fused function promotes tumorigenesis. Oncogene 26: 6442–6447.
24. Lee MJ, Hatton BA, Villavicencio EH, Khanna PC, Friedman SD, Ditzler S, et al. (2012). Hedgehog pathway inhibitor saridegib (IPI-926) increases lifespan in a mouse medulloblastoma model. Proc Natl Acad Sci USA 109: 7859–7864.
25. May S, Ashique A, Karlen M, Wang B, Shen Y, Zarbalis K, et al. (2005). Loss of the retrograde motor for IFT disrupts localization of Smo to cilia and prevents the expression of both activator and repressor functions of Gli. Dev Biol 287: 378.
26. Northcott PA, Nakahara Y, Wu X, Feuk L, Ellison DW, Croul S, et al. (2009). Multiple recurrent genetic events converge on control of histone lysine methylation in medulloblastoma. Nat Genet 41: 465–472.
27. Park H, Bai C, Platt K, Matise M, Beeghly A, Hui C, et al. (2000). Mouse Gli1 mutants are viable but have defects in SHH signaling in combination with a Gli2 mutation. Development 127: 1593–1605.
28. Raffel C, Jenkins RB, Frederick L, Hebrink D, Alderete B, Fults DW, et al. (1997). Sporadic medulloblastomas contain PTCH mutations. Cancer Res 57: 842–845.
29. Rohatgi R, Milenkovic L, Scott MP (2007). Patched1 regulates hedgehog signaling at the primary cilium. Sci Signal 317: 372.
30. 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.
31. Rudin CM, Hann CL, Laterra J, Yauch RL, Callahan CA, Fu L, et al. (2009). Treatment of medulloblastoma with hedgehog pathway inhibitor GDC-0449. N Engl J Med 361: 1173–1178.
32. Sambrook J, Russell DW (2001) Pp. 1357–1361 in Molecular cloning: a laboratory manual (3-volume set), Chap. 17. Cold Spring Harbor Laboratory Press, New York.
33. Taylor MD, Liu L, Raffel C, C-C Hui, Mainprize TG, Zhang X, et al. (2002). Mutations in SUFU predispose to medulloblastoma. Nat Genet 31: 306–310.
34. Tran PV, Haycraft CJ, Besschetnova TY, Turbe-Doan A, Stottmann RW, Herron BJ, et al. (2008). THM1 negatively modulates mouse sonic hedgehog signal transduction and affects retrograde intraflagellar transport in cilia. Nat Genet 40: 403–410.
35. Tremblay MR, Lescarbeau A, Grogan MJ, Tan E, Lin G, Austad BC, et al. (2009). Discovery of a potent and orally active hedgehog pathway antagonist (IPI-926). J Med Chem 52: 4400–4418.
36. Vigushin D, Coombes R (2004). Targeted histone deacetylase inhibition for cancer therapy. Curr Cancer Drug Targets 4: 205–218.
37. 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.
38. Wang Y, Arvanites AC, Davidow L, Blanchard J, Lam K, Yoo JW, et al. (2012). Selective identification of hedgehog pathway antagonists by direct analysis of smoothened ciliary translocation. ACS Chem Biol 7: 1040–1048.
39. Wilson CW, Chen M-H, Chuang P-T (2009). Smoothened adopts multiple active and inactive conformations capable of trafficking to the primary cilium. PLoS ONE 4: e5182.
40. Xie J, Murone M, Luoh S-M, Ryan A, Gu Q, Zhang C, et al. (1998). Activating Smoothened mutations in sporadic basal-cell carcinoma. Nature 391: 90–92.
41. Yauch RL, Dijkgraaf GJ, Alicke B, Januario T, Ahn CP, Holcomb T, et al. (2009). Smoothened mutation confers resistance to a Hedgehog pathway inhibitor in medulloblastoma. Sci Signal 326: 572.