BHLH transcription factors inhibitors for cancer therapy: General features for in silico drug design

Current Medicinal Chemistry

Volumn 21, Issue 28, 2014, Pages 3227-3243

  Tsigelny, I F ^a,b,c   Kouznetsova, V L ^b,c   Pingle, S C ^c   Kesari, S ^a,c  

^a UNIVERSITY OF CALIFORNIA   (United States)

^b UNIVERSITY OF CALIFORNIA   (United States)

^c UNIVERSITY OF CALIFORNIA SAN DIEGO   (United States)

Author keywords

BHLH; Cancer; Computational drug design; Drug dna interactions; Drug protein interactions; In silico; Inhibitors; Protein dimerization; Transcription factor

Indexed keywords

BASIC HELIX LOOP HELIX TRANSCRIPTION FACTOR; DNA; MICRORNA;

ANTAGONISTS AND INHIBITORS; CHEMISTRY; COMPUTER SIMULATION; DRUG DESIGN; HUMAN; METABOLISM; NEOPLASMS; PROTEIN MULTIMERIZATION; PROTEIN TERTIARY STRUCTURE;

BASIC HELIX-LOOP-HELIX TRANSCRIPTION FACTORS; COMPUTER SIMULATION; DNA; DRUG DESIGN; HUMANS; MICRORNAS; NEOPLASMS; PROTEIN MULTIMERIZATION; PROTEIN STRUCTURE, TERTIARY;

EID: 84906920668     PISSN: 09298673     EISSN: 1875533X     Source Type: Journal    
DOI: 10.2174/0929867321666140414111333     Document Type: Article

References (145)

1. Karin, M. Too many transcription factors: positive and negative interactions. New Biol., 1990, 2(2), 126-131.
2. Latchman, D. S. Transcription factors: an overview. Int. J. Biochem. Cell Biol., 1997, 29(12), 1305-1312.
3. Mitchell, P. J.; Tjian, R. Transcriptional regulation in mammalian cells by sequence-specific DNA binding proteins. Science, 1989, 245(4916), 371-378.
4. Ptashne, M.; Gann, A. Transcriptional activation by recruitment. Nature, 1997, 386(6625), 569-577.
5. Massari, M. E.; Murre, C. Helix-loop-helix proteins: regulators of transcription in eucaryotic organisms. Mol. Cell. Biol., 2000, 20(2), 429-440.
6. Perk, J.; Iavarone, A.; Benezra, R. Id family of helix-loop-helix proteins in cancer. Nat. Rev. Cancer, 2005, 5(8), 603-614.
7. Atchley, W. R.; Fitch, W. M. A natural classification of the basic helix-loop-helix class of transcription factors. Proc. Natl. Acad. Sci. U. S. A., 1997, 94(10), 5172-5176.
8. Ledent, V.; Paquet, O.; Vervoort, M. Phylogenetic analysis of the human basic helix-loop-helix proteins. Genome Biol., 2002, 3(6), RESEARCH0030.1, RESEARCH0030.18.
9. Buck, M. J.; Atchley, W. R. Phylogenetic analysis of plant basic helix-loop-helix proteins. J. Mol. Evol., 2003, 56(6), 742-750.
10. Heim, M. A.; Jakoby, M.; Werber, M.; Martin, C.; Weisshaar, B.; Bailey, P. C. The basic helix-loop-helix transcription factor family in plants: a genome-wide study of protein structure and functional diversity. Mol. Biol. Evol., 2003, 20(5), 735-747.
11. Toledo-Ortiz, G.; Huq, E.; Quail, P. H. The Arabidopsis basic/helixloop-helix transcription factor family. Plant Cell, 2003, 15(8), 1749-70.
12. Skinner, M. K.; Rawls, A.; Wilson-Rawls, J.; Roalson, E. H. Basic helix-loop-helix transcription factor gene family phylogenetics and nomenclature. Differentiation, 2010, 80(1), 1-8.
13. Stevens, J. D.; Roalson, E. H.; Skinner, M. K. Phylogenetic and expression analysis of the basic helix-loop-helix transcription factor gene family: genomic approach to cellular differentiation. Differentiation, 2008, 76(9), 1006-1022.
14. Patel, D.; Chaudhary, J. Increased expression of bHLH transcription factor E2A (TCF3) in prostate cancer promotes proliferation and confers resistance to doxorubicin induced apoptosis. Biochem. Biophys. Res. Commun., 2012, 422(1), 146-151.
15. Alexander, N. R.; Tran, N. L.; Rekapally, H.; Summers, C. E.; Glackin, C.; Heimark, R. L. N-cadherin gene expression in prostate carcinoma is modulated by integrin-dependent nuclear translocation of Twist1. Cancer Res., 2006, 66(7), 3365-3369.
16. Peinado, H.; Olmeda, D.; Cano, A. Snail, Zeb and bHLH factors in tumour progression: an alliance against the epithelial phenotype? Nat. Rev. Cancer, 2007, 7(6), 415-428.
17. Perez-Moreno, M. A.; Locascio, A.; Rodrigo, I.; Dhondt, G.; Portillo, F.; Nieto, M. A.; Cano, A. A new role for E12/E47 in the repression of E-cadherin expression and epithelial-mesenchymal transitions. J. Biol. Chem., 2001, 276(29), 27424-27431.
18. Zhao, H.; Huang, A.; Li, P.; Quan, Y.; Feng, B.; Chen, X.; Mao, Z.; Zhu, Z.; Zheng, M. E2A suppresses invasion and migration by targeting YAP in colorectal cancer cells. J. Transl. Med., 2013, 11, 317.
19. Sanchez-Tillo, E.; Liu, Y.; de Barrios, O.; Siles, L.; Fanlo, L.; Cuatrecasas, M.; Darling, D. S.; Dean, D. C.; Castells, A.; Postigo, A. EMT-activating transcription factors in cancer: beyond EMT and tumor invasiveness. Cell. Mol. Life Sci., 2012, 69(20), 3429-3456.
20. Sobrado, V. R.; Moreno-Bueno, G.; Cubillo, E.; Holt, L. J.; Nieto, M. A.; Portillo, F.; Cano, A. The class I bHLH factors E2-2A and E2-2B regulate EMT. J. Cell Sci., 2009, 122(Pt 7), 1014-1024.
21. Je, E.-C.; Lca, B. S.; Ga, G. A. The role of transcription factor TWIST in cancer cells. J. Genet. Syndr. Gene Ther., 2013, 4(1), 124.
22. Hoek, K.; Rimm, D. L.; Williams, K. R.; Zhao, H.; Ariyan, S.; Lin, A.; Kluger, H. M.; Berger, A. J.; Cheng, E.; Trombetta, E. S.; Wu, T.; Niinobe, M.; Yoshikawa, K.; Hannigan, G. E.; Halaban, R. Expression profiling reveals novel pathways in the transformation of melanocytes to melanomas. Cancer Res., 2004, 64(15), 5270-5282.
23. Kyo, S.; Sakaguchi, J.; Ohno, S.; Mizumoto, Y.; Maida, Y.; Hashimoto, M.; Nakamura, M.; Takakura, M.; Nakajima, M.; Masutomi, K.; Inoue, M. High Twist expression is involved in infiltrative endometrial cancer and affects patient survival. Hum. Pathol., 2006, 37(4), 431-438.
24. Sharma, V. P.; Fenwick, A. L.; Brockop, M. S.; McGowan, S. J.; Goos, J. A.; Hoogeboom, A. J.; Brady, A. F.; Jeelani, N. O.; Lynch, S. A.; Mulliken, J. B.; Murray, D. J.; Phipps, J. M.; Sweeney, E.; Tomkins, S. E.; Wilson, L. C.; Bennett, S.; Cornall, R. J.; Broxholme, J.; Kanapin, A.; Whole-Genome Sequences, C.; Johnson, D.; Wall, S. A.; van der Spek, P. J.; Mathijssen, I. M.; Maxson, R. E.; Twigg, S. R.; Wilkie, A. O. Mutations in TCF12, encoding a basic helix-loop-helix partner of TWIST1, are a frequent cause of coronal craniosynostosis. Nat. Genet., 2013, 45(3), 304-307.
25. Tapanes-Castillo, A.; Baylies, M. K. Notch signaling patterns Drosophila mesodermal segments by regulating the bHLH transcription factor twist. Development, 2004, 131(10), 2359-2372.
26. Bersten, D. C.; Sullivan, A. E.; Peet, D. J.; Whitelaw, M. L. bHLH-PAS proteins in cancer. Nat. Rev. Cancer, 2013, 13(12), 827-841.
27. Labrecque, M. P.; Prefontaine, G. G.; Beischlag, T. V. The aryl hydrocarbon receptor nuclear translocator (ARNT) family of proteins: transcriptional modifiers with multi-functional protein interfaces. Curr. Mol. Med., 2013, 13(7), 1047-65.
28. Andersson, P.; McGuire, J.; Rubio, C.; Gradin, K.; Whitelaw, M. L.; Pettersson, S.; Hanberg, A.; Poellinger, L. A constitutively active dioxin/aryl hydrocarbon receptor induces stomach tumors. Proc. Natl. Acad. Sci. U. S. A., 2002, 99(15), 9990-9995.
29. Moennikes, O.; Loeppen, S.; Buchmann, A.; Andersson, P.; Ittrich, C.; Poellinger, L.; Schwarz, M. A constitutively active dioxin/aryl hydrocarbon receptor promotes hepatocarcinogenesis in mice. Cancer Res., 2004, 64(14), 4707-4710.
30. Opitz, C. A.; Litzenburger, U. M.; Sahm, F.; Ott, M.; Tritschler, I.; Trump, S.; Schumacher, T.; Jestaedt, L.; Schrenk, D.; Weller, M.; Jugold, M.; Guillemin, G. J.; Miller, C. L.; Lutz, C.; Radlwimmer, B.; Lehmann, I.; von Deimling, A.; Wick, W.; Platten, M. An endogenous tumour-promoting ligand of the human aryl hydrocarbon receptor. Nature, 2011, 478(7368), 197-203.
31. Gramatzki, D.; Pantazis, G.; Schittenhelm, J.; Tabatabai, G.; Kohle, C.; Wick, W.; Schwarz, M.; Weller, M.; Tritschler, I. Aryl hydrocarbon receptor inhibition downregulates the TGF-beta/Smad pathway in human glioblastoma cells. Oncogene, 2009, 28(28), 2593-2605.
32. Wang, G. L.; Jiang, B. H.; Rue, E. A.; Semenza, G. L. Hypoxiainducible factor 1 is a basic-helix-loop-helix-PAS heterodimer regulated by cellular O2 tension. Proc. Natl. Acad. Sci. U. S. A., 1995, 92(12), 5510-5514.
33. Semenza, G. L. Hypoxia-inducible factors: mediators of cancer progression and targets for cancer therapy. Trends Pharmacol. Sci., 2012, 33(4), 207-214.
34. Semenza, G. L. Hypoxia-inducible factors in physiology and medicine. Cell, 2012, 148(3), 399-408.
35. Zhao, S.; Lin, Y.; Xu, W.; Jiang, W.; Zha, Z.; Wang, P.; Yu, W.; Li, Z.; Gong, L.; Peng, Y.; Ding, J.; Lei, Q.; Guan, K. L.; Xiong, Y. Glioma-derived mutations in IDH1 dominantly inhibit IDH1 catalytic activity and induce HIF-1alpha. Science, 2009, 324(5924), 261-265.
36. Lu, Q. R.; Park, J. K.; Noll, E.; Chan, J. A.; Alberta, J.; Yuk, D.; Alzamora, M. G.; Louis, D. N.; Stiles, C. D.; Rowitch, D. H.; Black, P. M. Oligodendrocyte lineage genes (OLIG) as molecular markers for human glial brain tumors. Proc. Natl. Acad. Sci. U. S. A., 2001, 98(19), 10851-10856.
37. Zhou, Q.; Wang, S.; Anderson, D. J. Identification of a novel family of oligodendrocyte lineage-specific basic helix-loop-helix transcription factors. Neuron, 2000, 25(2), 331-343.
38. Zhou, Q.; Choi, G.; Anderson, D. J. The bHLH transcription factor Olig2 promotes oligodendrocyte differentiation in collaboration with Nkx2.2. Neuron, 2001, 31(5), 791-807.
39. Arnett, H. A.; Fancy, S. P.; Alberta, J. A.; Zhao, C.; Plant, S. R.; Kaing, S.; Raine, C. S.; Rowitch, D. H.; Franklin, R. J.; Stiles, C. D. bHLH transcription factor Olig1 is required to repair demyelinated lesions in the CNS. Science, 2004, 306(5704), 2111-2115.
40. Marie, Y.; Sanson, M.; Mokhtari, K.; Leuraud, P.; Kujas, M.; Delattre, J. Y.; Poirier, J.; Zalc, B.; Hoang-Xuan, K. OLIG2 as a specific marker of oligodendroglial tumour cells. Lancet, 2001, 358(9278), 298-300.
41. Lin, Y. W.; Deveney, R.; Barbara, M.; Iscove, N. N.; Nimer, S. D.; Slape, C.; Aplan, P. D. OLIG2(BHLHB1), a bHLH transcription factor, contributes to leukemogenesis in concert with LMO1. Cancer Res., 2005, 65(16), 7151-7158.
42. Wu, Y.; Sato, F.; Bhawal, U. K.; Kawamoto, T.; Fujimoto, K.; Noshiro, M.; Morohashi, S.; Kato, Y.; Kijima, H. Basic helix-loophelix transcription factors DEC1 and DEC2 regulate the paclitaxelinduced apoptotic pathway of MCF-7 human breast cancer cells. Int. J. Mol. Med., 2011, 27(4), 491-495.
43. Wu, Y.; Sato, F.; Bhawal, U. K.; Kawamoto, T.; Fujimoto, K.; Noshiro, M.; Seino, H.; Morohashi, S.; Kato, Y.; Kijima, H. BHLH transcription factor DEC2 regulates pro-apoptotic factor Bim in human oral cancer HSC-3 cells. Biomed. Res., 2012, 33(2), 75-82.
44. Ruzinova, M. B.; Benezra, R. Id proteins in development, cell cycle and cancer. Trends Cell Biol., 2003, 13(8), 410-418.
45. Sumida, T.; Murase, R.; Onishi-Ishikawa, A.; McAllister, S. D.; Hamakawa, H.; Desprez, P. Y. Targeting Id1 reduces proliferation and invasion in aggressive human salivary gland cancer cells. BMC Cancer, 2013, 13, 141.
46. Wang, X.; Ling, M. T.; Guan, X. Y.; Tsao, S. W.; Cheung, H. W.; Lee, D. T.; Wong, Y. C. Identification of a novel function of TWIST, a bHLH protein, in the development of acquired taxol resistance in human cancer cells. Oncogene, 2004, 23(2), 474-482.
47. Gyorffy, A.; Vasarhelyi, B.; Szoke, D.; Dietel, M.; Tulassay, T.; Gyorffy, B. Comparative promoter analysis of doxorubicin resistance-associated genes suggests E47 as a key regulatory element. Anticancer Res., 2006, 26(4B), 2971-2976.
48. Zhong, J.; Ogura, K.; Wang, Z.; Inuzuka, H. Degradation of the transcription factor Twist, an oncoprotein that promotes cancer metastasis. Discov. Med., 2013, 15(80), 7-15.
49. Hefti, M. H.; Francoijs, K. J.; de Vries, S. C.; Dixon, R.; Vervoort, J. The PAS fold. A redefinition of the PAS domain based upon structural prediction. Eur. J. Biochem., 2004, 271(6), 1198-1208.
50. Ponting, C. P.; Aravind, L. PAS: a multifunctional domain family comes to light. Curr. Biol., 1997, 7(11), R674-R677.
51. Hao, N.; Bhakti, V. L.; Peet, D. J.; Whitelaw, M. L. Reciprocal regulation of the basic helix-loop-helix/Per-Arnt-Sim partner proteins, Arnt and Arnt2, during neuronal differentiation. Nucleic Acids Res., 2013, 41(11), 5626-5638.
52. Martinez, V.; Kennedy, S.; Doolan, P.; Gammell, P.; Joyce, H.; Kenny, E.; Prakash Mehta, J.; Ryan, E.; O'Connor, R.; Crown, J.; Clynes, M.; O'Driscoll, L. Drug metabolism-related genes as potential biomarkers: analysis of expression in normal and tumour breast tissue. Breast Cancer Res. Treat., 2008, 110(3), 521-530.
53. Prochownik, E. V.; Vogt, P. K. Therapeutic targeting of Myc. Genes Cancer, 2010, 1(6), 650-659.
54. Yap, J. L.; Chauhan, J.; Jung, K.-Y.; Chen, L.; Prochownik, E. V.; Fletcher, S. Small-molecule inhibitors of dimeric transcription factors: antagonism of protein-protein and protein-DNA interactions. Med. Chem. Comm., 2012, 3(5), 541-551.
55. Axelson, H. The Notch signaling cascade in neuroblastoma: role of the basic helix-loop-helix proteins HASH-1 and HES-1. Cancer Lett., 2004, 204(2), 171-178.
56. Sang, L.; Roberts, J. M.; Coller, H. A. Hijacking HES1: how tumors co-opt the anti-differentiation strategies of quiescent cells. Trends Mol. Med., 2010, 16(1), 17-26.
57. Fouladi, M.; Stewart, C. F.; Olson, J.; Wagner, L. M.; Onar-Thomas, A.; Kocak, M.; Packer, R. J.; Goldman, S.; Gururangan, S.; Gajjar, A.; Demuth, T.; Kun, L. E.; Boyett, J. M.; Gilbertson, R. J. Phase I trial of MK-0752 in children with refractory CNS malignancies: a pediatric brain tumor consortium study. J. Clin. Oncol., 2011, 29(26), 3529-3534.
58. Wei, P.; Walls, M.; Qiu, M.; Ding, R.; Denlinger, R. H.; Wong, A.; Tsaparikos, K.; Jani, J. P.; Hosea, N.; Sands, M.; Randolph, S.; Smeal, T. Evaluation of selective gamma-secretase inhibitor PF-03084014 for its antitumor efficacy and gastrointestinal safety to guide optimal clinical trial design. Mol. Cancer Ther., 2010, 9(6), 1618-1628.
59. Lee, M. J.; Hatton, B. A.; Villavicencio, E. H.; Khanna, P. C.; Friedman, S. D.; Ditzler, S.; Pullar, B.; Robison, K.; White, K. F.; Tunkey, C.; Le Blanc, M.; Randolph-Habecker, J.; Knoblaugh, S. E.; Hansen, S.; Richards, A.; Wainwright, B. J.; McGovern, K.; Olson, J. M. Hedgehog pathway inhibitor saridegib (IPI-926) increases lifespan in a mouse medulloblastoma model. Proc. Natl. Acad. Sci. U. S. A., 2012, 109(20), 7859-7864.
60. Yauch, R. L.; Dijkgraaf, G. J.; Alicke, B.; Januario, T.; Ahn, C. P.; Holcomb, T.; Pujara, K.; Stinson, J.; Callahan, C. A.; Tang, T.; Bazan, J. F.; Kan, Z.; Seshagiri, S.; Hann, C. L.; Gould, S. E.; Low, J. A.; Rudin, C. M.; de Sauvage, F. J. Smoothened mutation confers resistance to a Hedgehog pathway inhibitor in medulloblastoma. Science, 2009, 326(5952), 572-574.
61. Arai, M. A.; Masada, A.; Ohtsuka, T.; Kageyama, R.; Ishibashi, M. The first Hes1 dimer inhibitors from natural products. Bioorg. Med. Chem. Lett., 2009, 19(19), 5778-5781.
62. Cascon, A.; Robledo, M. MAX and MYC: a heritable breakup. Cancer Res., 2012, 72(13), 3119-3124.
63. Berg, T. Inhibition of transcription factors with small organic molecules. Curr. Opin. Chem. Biol., 2008, 12(4), 464-471.
64. Boger, D. L.; Lee, J. K.; Goldberg, J.; Jin, Q. Two comparisons of the performance of positional scanning and deletion synthesis for the identification of active constituents in mixture combinatorial libraries. J. Org. Chem., 2000, 65(5), 1467-1474.
65. Berg, T.; Cohen, S. B.; Desharnais, J.; Sonderegger, C.; Maslyar, D. J.; Goldberg, J.; Boger, D. L.; Vogt, P. K. Small-molecule antagonists of Myc/Max dimerization inhibit Myc-induced transformation of chicken embryo fibroblasts. Proc. Natl. Acad. Sci. U. S. A., 2002, 99(6), 3830-3835.
66. Shi, J.; Stover, J. S.; Whitby, L. R.; Vogt, P. K.; Boger, D. L. Small molecule inhibitors of Myc/Max dimerization and Myc-induced cell transformation. Bioorg. Med. Chem. Lett., 2009, 19(21), 6038-6041.
67. Berg, T. Small-molecule modulators of c-Myc/Max and Max/Max interactions. Curr. Top. Microbiol. Immunol., 2011, 348, 139-149.
68. Yin, X.; Giap, C.; Lazo, J. S.; Prochownik, E. V. Low molecular weight inhibitors of Myc-Max interaction and function. Oncogene, 2003, 22(40), 6151-6159.
69. Wang, H.; Hammoudeh, D. I.; Follis, A. V.; Reese, B. E.; Lazo, J. S.; Metallo, S. J.; Prochownik, E. V. Improved low molecular weight Myc-Max inhibitors. Mol. Cancer Ther., 2007, 6(9), 2399-2408.
70. Kiessling, A.; Sperl, B.; Hollis, A.; Eick, D.; Berg, T. Selective inhibition of c-Myc/Max dimerization and DNA binding by small molecules. Chem. Biol., 2006, 13(7), 745-751.
71. Kiessling, A.; Wiesinger, R.; Sperl, B.; Berg, T. Selective inhibition of c-Myc/Max dimerization by a pyrazolo[1, 5-a]pyrimidine. Chem. Med. Chem., 2007, 2(5), 627-630.
72. Xu, Y.; Shi, J.; Yamamoto, N.; Moss, J. A.; Vogt, P. K.; Janda, K. D. A credit-card library approach for disrupting protein-protein interactions. Bioorg. Med. Chem., 2006, 14(8), 2660-2673.
73. Ghosh, I.; Chmielewski, J. A beta-sheet peptide inhibitor of E47 dimerization and DNA binding. Chem. Biol., 1998, 5(8), 439-445.
74. Chen, C. H.; Kuo, S. C.; Huang, L. J.; Hsu, M. H.; Lung, F. D. Affinity of synthetic peptide fragments of MyoD for Id1 protein and their biological effects in several cancer cells. J. Pept. Sci., 2010, 16(5), 231-241.
75. Jakovcevski, I.; Zecevic, N. Olig transcription factors are expressed in oligodendrocyte and neuronal cells in human fetal CNS. J. Neurosci., 2005, 25(44), 10064-10073.
76. Appolloni, I.; Calzolari, F.; Barilari, M.; Terrile, M.; Daga, A.; Malatesta, P. Antagonistic modulation of gliomagenesis by Pax6 and Olig2 in PDGF-induced oligodendroglioma. Int. J. Cancer, 2012, 131(7), E1078-E1087.
77. Dietrich, J.; Imitola, J.; Kesari, S. Mechanisms of disease: the role of stem cells in the biology and treatment of gliomas. Nat. Clin. Pract.. Oncol., 2008, 5(7), 393-404.
78. Ligon, K. L.; Alberta, J. A.; Kho, A. T.; Weiss, J.; Kwaan, M. R.; Nutt, C. L.; Louis, D. N.; Stiles, C. D.; Rowitch, D. H. The oligodendroglial lineage marker OLIG2 is universally expressed in diffuse gliomas. J. Neuropathol. Exp. Neurol., 2004, 63(5), 499-509.
79. Ligon, K. L.; Huillard, E.; Mehta, S.; Kesari, S.; Liu, H.; Alberta, J. A.; Bachoo, R. M.; Kane, M.; Louis, D. N.; Depinho, R. A.; Anderson, D. J.; Stiles, C. D.; Rowitch, D. H. Olig2-regulated lineagerestricted pathway controls replication competence in neural stem cells and malignant glioma. Neuron, 2007, 53(4), 503-517.
80. Mehta, S.; Huillard, E.; Kesari, S.; Maire, C. L.; Golebiowski, D.; Harrington, E. P.; Alberta, J. A.; Kane, M. F.; Theisen, M.; Ligon, K. L.; Rowitch, D. H.; Stiles, C. D. The central nervous systemrestricted transcription factor Olig2 opposes p53 responses to genotoxic damage in neural progenitors and malignant glioma. Cancer Cell, 2011, 19(3), 359-371.
81. Wen, P. Y.; Kesari, S. Malignant gliomas in adults. N. Engl. J. Med., 2008, 359(5), 492-507.
82. Osborne, J. K.; Larsen, J. E.; Shields, M. D.; Gonzales, J. X.; Shames, D. S.; Sato, M.; Kulkarni, A.; Wistuba, II; Girard, L.; Minna, J. D.; Cobb, M. H. NeuroD1 regulates survival and migration of neuroendocrine lung carcinomas via signaling molecules TrkB and NCAM. Proc. Natl. Acad. Sci. U. S. A., 2013, 110(16), 6524-6529.
83. Carmeliet, P.; Dor, Y.; Herbert, J. M.; Fukumura, D.; Brusselmans, K.; Dewerchin, M.; Neeman, M.; Bono, F.; Abramovitch, R.; Maxwell, P.; Koch, C. J.; Ratcliffe, P.; Moons, L.; Jain, R. K.; Collen, D.; Keshert, E. Role of HIF-1alpha in hypoxia-mediated apoptosis, cell proliferation and tumour angiogenesis. Nature, 1998, 394(6692), 485-490.
84. Jiang, B. H.; Rue, E.; Wang, G. L.; Roe, R.; Semenza, G. L. Dimerization, DNA binding, and transactivation properties of hypoxiainducible factor 1. J. Biol. Chem., 1996, 271(30), 17771-17778.
85. Maxwell, P. H.; Dachs, G. U.; Gleadle, J. M.; Nicholls, L. G.; Harris, A. L.; Stratford, I. J.; Hankinson, O.; Pugh, C. W.; Ratcliffe, P. J. Hypoxia-inducible factor-1 modulates gene expression in solid tumors and influences both angiogenesis and tumor growth. Proc. Natl. Acad. Sci. U. S. A., 1997, 94(15), 8104-8109.
86. Park, E. J.; Kong, D.; Fisher, R.; Cardellina, J.; Shoemaker, R. H.; Melillo, G. Targeting the PAS-A domain of HIF-1alpha for development of small molecule inhibitors of HIF-1. Cell Cycle, 2006, 5(16), 1847-1853.
87. Nordgren, I. K.; Tavassoli, A. Targeting tumour angiogenesis with small molecule inhibitors of hypoxia inducible factor. Chem. Soc. Rev., 2011, 40(8), 4307-4317.
88. Rogers, J. L.; Bayeh, L.; Scheuermann, T. H.; Longgood, J.; Key, J.; Naidoo, J.; Melito, L.; Shokri, C.; Frantz, D. E.; Bruick, R. K.; Gardner, K. H.; MacMillan, J. B.; Tambar, U. K. Development of inhibitors of the PAS-B domain of the HIF-2alpha transcription factor. J. Med. Chem., 2013, 56(4), 1739-1747.
89. Scheuermann, T. H.; Li, Q.; Ma, H. W.; Key, J.; Zhang, L.; Chen, R.; Garcia, J. A.; Naidoo, J.; Longgood, J.; Frantz, D. E.; Tambar, U. K.; Gardner, K. H.; Bruick, R. K. Allosteric inhibition of hypoxia inducible factor-2 with small molecules. Nat. Chem. Biol., 2013, 9(4), 271-276.
90. Lee, K.; Zhang, H.; Qian, D. Z.; Rey, S.; Liu, J. O.; Semenza, G. L. Acriflavine inhibits HIF-1 dimerization, tumor growth, and vascularization. Proc. Natl. Acad. Sci. U. S. A., 2009, 106(42), 17910-17915.
91. Draeger, L. J.; Mullen, G. P. Interaction of the bHLH-zip domain of c-Myc with H1-type peptides. Characterization of helicity in the H1 peptides by NMR. J. Biol. Chem., 1994, 269(3), 1785-1793.
92. D'Agnano, I.; Valentini, A.; Gatti, G.; Chersi, A.; Felsani, A. Oligopeptides impairing the Myc-Max heterodimerization inhibit lung cancer cell proliferation by reducing Myc transcriptional activity. J. Cell. Physiol., 2007, 210(1), 72-80.
93. Lavigne, P.; Crump, M. P.; Gagne, S. M.; Hodges, R. S.; Kay, C. M.; Sykes, B. D. Insights into the mechanism of heterodimerization from the 1H-NMR solution structure of the c-Myc-Max heterodimeric leucine zipper. J. Mol. Biol., 1998, 281(1), 165-181.
94. Lavigne, P.; Kondejewski, L. H.; Houston, M. E., Jr.; Sonnichsen, F. D.; Lix, B.; Skyes, B. D.; Hodges, R. S.; Kay, C. M. Preferential heterodimeric parallel coiled-coil formation by synthetic Max and c-Myc leucine zippers: a description of putative electrostatic interactions responsible for the specificity of heterodimerization. J. Mol. Biol., 1995, 254(3), 505-520.
95. Mo, H.; Henriksson, M. Identification of small molecules that induce apoptosis in a Myc-dependent manner and inhibit Mycdriven transformation. Proc. Natl. Acad. Sci. U. S. A., 2006, 103(16), 6344-6349.
96. Chung, S.; Park, S.; Yang, C. H. Unsaturated fatty acids bind Myc-Max transcription factor and inhibit Myc-Max-DNA complex formation. Cancer Lett., 2002, 188(1-2), 153-162.
97. Jung, K. C.; Park, C. H.; Hwang, Y. H.; Rhee, H. S.; Lee, J. H.; Kim, H. K.; Yang, C. H. Fatty acids, inhibitors for the DNA binding of c-Myc/Max dimer, suppress proliferation and induce apoptosis of differentiated HL-60 human leukemia cell. Leukemia, 2006, 20(1), 122-127.
98. Kong, D.; Park, E. J.; Stephen, A. G.; Calvani, M.; Cardellina, J. H.; Monks, A.; Fisher, R. J.; Shoemaker, R. H.; Melillo, G. Echinomycin, a small-molecule inhibitor of hypoxia-inducible factor-1 DNA-binding activity. Cancer Res., 2005, 65(19), 9047-9055.
99. Leung, C. H.; Chan, D. S.; Ma, V. P.; Ma, D. L. DNA-binding small molecules as inhibitors of transcription factors. Med. Res. Rev., 2013, 33(4), 823-846.
100. Olenyuk, B. Z.; Zhang, G. J.; Klco, J. M.; Nickols, N. G.; Kaelin, W. G., Jr.; Dervan, P. B. Inhibition of vascular endothelial growth factor with a sequence-specific hypoxia response element antagonist. Proc. Natl. Acad. Sci. U. S. A., 2004, 101(48), 16768-16773.
101. Sokkar, P.; Sathis, V.; Ramachandran, M. Computational modeling on the recognition of the HRE motif by HIF-1: molecular docking and molecular dynamics studies. J. Mol. Model., 2012, 18(5), 1691-1700.
102. Ha, H. H.; Kim, B. M. Discovery of novel transcription factor inhibitors using a pyrazole-based small molecule library. Bull. Korean Chem. Soc., 2008, 29(2), 323-327.
103. Ema, M.; Hirota, K.; Mimura, J.; Abe, H.; Yodoi, J.; Sogawa, K.; Poellinger, L.; Fujii-Kuriyama, Y. Molecular mechanisms of transcription activation by HLF and HIF1alpha in response to hypoxia: their stabilization and redox signal-induced interaction with CBP/p300. EMBO J., 1999, 18(7), 1905-1914.
104. Jones, D. T.; Harris, A. L. Identification of novel small-molecule inhibitors of hypoxia-inducible factor-1 transactivation and DNA binding. Mol. Cancer Ther., 2006, 5(9), 2193-2202.
105. Minchenko, A.; Salceda, S.; Bauer, T.; Caro, J. Hypoxia regulatory elements of the human vascular endothelial growth factor gene. Cell. Mol. Biol. Res., 1994, 40(1), 35-39.
106. Stockhausen, M. T.; Sjolund, J.; Manetopoulos, C.; Axelson, H. Effects of the histone deacetylase inhibitor valproic acid on Notch signalling in human neuroblastoma cells. Br. J. Cancer, 2005, 92(4), 751-759.
107. Jang, M.; Cai, L.; Udeani, G. O.; Slowing, K. V.; Thomas, C. F.; Beecher, C. W.; Fong, H. H.; Farnsworth, N. R.; Kinghorn, A. D.; Mehta, R. G.; Moon, R. C.; Pezzuto, J. M. Cancer chemopreventive activity of resveratrol, a natural product derived from grapes. Science, 1997, 275(5297), 218-220.
108. Greenblatt, D. Y.; Vaccaro, A. M.; Jaskula-Sztul, R.; Ning, L.; Haymart, M.; Kunnimalaiyaan, M.; Chen, H. Valproic acid activates Notch-1 signaling and regulates the neuroendocrine phenotype in carcinoid cancer cells. Oncologist, 2007, 12(8), 942-951.
109. Angelucci, A.; Valentini, A.; Millimaggi, D.; Gravina, G. L.; Miano, R.; Dolo, V.; Vicentini, C.; Bologna, M.; Federici, G.; Bernardini, S. Valproic acid induces apoptosis in prostate carcinoma cell lines by activation of multiple death pathways. Anticancer Drugs, 2006, 17(10), 1141-1150.
110. Al-Hussaini, H.; Subramanyam, D.; Reedijk, M.; Sridhar, S. S. Notch signaling pathway as a therapeutic target in breast cancer. Mol. Cancer Ther., 2011, 10(1), 9-15.
111. Ingram, W. J.; McCue, K. I.; Tran, T. H.; Hallahan, A. R.; Wainwright, B. J. Sonic Hedgehog regulates Hes1 through a novel mechanism that is independent of canonical Notch pathway signalling. Oncogene, 2008, 27(10), 1489-1500.
112. Wall, D. S.; Mears, A. J.; McNeill, B.; Mazerolle, C.; Thurig, S.; Wang, Y.; Kageyama, R.; Wallace, V. A. Progenitor cell proliferation in the retina is dependent on Notch-independent Sonic hedgehog/Hes1 activity. J. Cell Biol., 2009, 184(1), 101-112.
113. Jimeno, A.; Weiss, G. J.; Miller, W. H., Jr.; Gettinger, S.; Eigl, B. J.; Chang, A. L.; Dunbar, J.; Devens, S.; Faia, K.; Skliris, G.; Kutok, J.; Lewis, K. D.; Tibes, R.; Sharfman, W. H.; Ross, R. W.; Rudin, C. M. Phase I study of the Hedgehog pathway inhibitor IPI-926 in adult patients with solid tumors. Clin. Cancer Res., 2013, 19(10), 2766-2774.
114. Singh, B. N.; Fu, J.; Srivastava, R. K.; Shankar, S. Hedgehog signaling antagonist GDC-0449 (Vismodegib) inhibits pancreatic cancer stem cell characteristics: molecular mechanisms. PLoS One, 2011, 6(11), e27306.
115. Li, Y.; Zhuang, P.; Shen, B.; Zhang, Y.; Shen, J. Baicalin promotes neuronal differentiation of neural stem/progenitor cells through modulating p-Stat3 and bHLH family protein expression. Brain Res., 2012, 1429, 36-42.
116. Zhu, R.; Yang, Y.; Tian, Y.; Bai, J.; Zhang, X.; Li, X.; Peng, Z.; He, Y.; Chen, L.; Pan, Q.; Fang, D.; Chen, W.; Qian, C.; Bian, X.; Wang, R. Ascl2 knockdown results in tumor growth arrest by miRNA-302b-related inhibition of colon cancer progenitor cells. PLoS One, 2012, 7(2), e32170.
117. Zhang, H.; Guo, Y.; Shang, C.; Song, Y.; Wu, B. miR-21 downregulated TCF21 to inhibit KISS1 in renal cancer. Urology, 2012, 80(6), 1298-1302 e1.
118. Chen, L.; Zhang, W.; Yan, W.; Han, L.; Zhang, K.; Shi, Z.; Zhang, J.; Wang, Y.; Li, Y.; Yu, S.; Pu, P.; Jiang, C.; Jiang, T.; Kang, C. The putative tumor suppressor miR-524-5p directly targets Jagged-1 and Hes-1 in glioma. Carcinogenesis, 2012, 33(11), 2276-2282.
119. Nairismagi, M. L.; Vislovukh, A.; Meng, Q.; Kratassiouk, G.; Beldiman, C.; Petretich, M.; Groisman, R.; Fuchtbauer, E. M.; Harel-Bellan, A.; Groisman, I. Translational control of TWIST1 expression in MCF-10A cell lines recapitulating breast cancer progression. Oncogene, 2012, 31(47), 4960-4966.
120. Ting, Y.; Medina, D. J.; Strair, R. K.; Schaar, D. G. Differentiationassociated miR-22 represses Max expression and inhibits cell cycle progression. Biochem. Biophys. Res. Commun., 2010, 394(3), 606-611.
121. Wibley, J.; Deed, R.; Jasiok, M.; Douglas, K.; Norton, J. A homology model of the Id-3 helix-loop-helix domain as a basis for structure-function predictions. Biochim. Biophys. Acta, 1996, 1294(2), 138-46.
122. Maia, A. M.; da Silva, J. H.; Mencalha, A. L.; Caffarena, E. R.; Abdelhay, E. Computational modeling of the bHLH domain of the transcription factor TWIST1 and R118C, S144R and K145E mutants. BMC Bioinformatics, 2012, 13, 184.
123. Michel, G.; Minet, E.; Ernest, I.; Roland, I.; Durant, F.; Remacle, J.; Michiels, C. A model for the complex between the hypoxiainducible factor-1 (HIF-1) and its consensus DNA sequence. J. Biomol. Struct. Dyn., 2000, 18(2), 169-179.
124. Atchley, W. R.; Wollenberg, K. R.; Fitch, W. M.; Terhalle, W.; Dress, A. W. Correlations among amino acid sites in bHLH protein domains: an information theoretic analysis. Mol. Biol. Evol., 2000, 17(1), 164-178.
125. Gadhwal, M. K.; Patil, S.; D'Mello, P.; Joshi, A. Homology modeling of aryl hydrocarbon receptor and docking of agonists and antagonists. Int. J. Pharm. Pharm. Sci., 2013, 5(2), 76-81.
126. Mustata, G.; Follis, A. V.; Hammoudeh, D. I.; Metallo, S. J.; Wang, H.; Prochownik, E. V.; Lazo, J. S.; Bahar, I. Discovery of novel Myc-Max heterodimer disruptors with a three-dimensional pharmacophore model. J. Med. Chem., 2009, 52(5), 1247-1250.
127. Yap, J. L.; Wang, H.; Hu, A.; Chauhan, J.; Jung, K. Y.; Gharavi, R. B.; Prochownik, E. V.; Fletcher, S. Pharmacophore identification of c-Myc inhibitor 10074-G5. Bioorg. Med. Chem. Lett., 2013, 23(1), 370-374.
128. Chung, J. Y.; Pasha, F. A.; Cho, S. J.; Won, M.; Lee, J. J.; Lee, K. Pharmacophore-based 3D-QSAR of HIF-1 inhibitors. Arch. Pharm. Res., 2009, 32(3), 317-23.
129. Lindin, I.; Wuxiuer, Y.; Kufareva, I.; Abagyan, R.; Moens, U.; Sylte, I.; Ravna, A. W. Homology modeling and ligand docking of mitogen-activated protein kinase-activated protein kinase 5 (MK5). Theor. Biol. Med. Model., 2013, 10, 56.
130. Abagyan, R.; Totrov, M.; Kuznetsov, D. ICM-A new method for protein modeling and design: Applications to docking and structure prediction from the distorted native conformation. J. Comput. Chem., 1994, 15(5), 488-506.
131. Nebert, D. W. Transcription factors and cancer: an overview. Toxicology, 2002, 181-182, 131-141.
132. Thompson, J. D.; Gibson, T. J.; Plewniak, F.; Jeanmougin, F.; Higgins, D. G. The CLUSTAL-X windows interface: flexible strategies for multiple sequence alignment aided by quality analysis tools. Nucleic Acids Res., 1997, 25(24), 4876-4882.
133. Guindon, S.; Gascuel, O. A simple, fast, and accurate algorithm to estimate large phylogenies by maximum likelihood. Syst. Biol., 2003, 52(5), 696-704.
134. Jones, D. T.; Taylor, W. R.; Thornton, J. M. The rapid generation of mutation data matrices from protein sequences. Comput. Appl. Biosci., 1992, 8(3), 275-282.
135. Ishikawa, Y.; Ishibashi, M.; Yamamoto, Y.; Hayashi, M.; Komiyama, K. Lindbladione and related naphthoquinone pigments from a myxomycete Lindbladia tubulina. Chem. Pharm. Bull. (Tokyo), 2002, 50(8), 1126-1127.
136. Buchanan, M. S.; Hashimoto, T.; Asakawa, Y. Phytyl esters and phaeophytins from the hornwort Megaceros flagellaris. Phytochemistry, 1996, 41(5), 1373-1376.
137. Fröde, R.; Hinze, C.; Josten, I.; Schmidt, B.; Steffan, B.; Steglich, W. Isolation and synthesis of 3, 4-bis (indol-3-yl) pyrrole-2, 5-dicarboxylic acid derivatives from the slime mould Lycogala epidendrum. Tetrahedron Lett., 1994, 35(11), 1689-1690.
138. Hashimoto, T.; Akiyo, Y.; Akazawa, K.; Takaoka, S.; Tori, M.; Asakawa, Y. Three novel dimethyl pyrroledicarboxylate, lycogarubins A-C, from the myxomycetes Lycogala epidendrum. Tetrahedron Lett., 1994, 35(16), 2559-2560.
139. Kamata, K.; Kiyota, M.; Naoe, A.; Nakatani, S.; Yamamoto, Y.; Hayashi, M.; Komiyama, K.; Yamori, T.; Ishibashi, M. New bisindole alkaloids isolated from myxomycetes Arcyria cinerea and Lycogala epidendrum. Chem. Pharm. Bull. (Tokyo), 2005, 53(5), 594-597.
140. Yahara, S.; Nakazono, M.; Tutumi, H.; Nohara, T. Lignans from leaves of Laurus nobilis L. Shoyakugaku Zasshi, 1992, 46(2), 184-186.
141. Hoshino, T.; Kojima, Y.; Hayashi, T.; Uchiyama, T.; Kaneko, K. A new metabolite of tryptophan, chromopyrrolic acid, produced by Chromobacterium violaceum. Biosci. Biotechnol. Biochem., 1993, 57(5), 775-781.
142. Sadhu, S. K.; Khan, M. S.; Ohtsuki, T.; Ishibashi, M. Secoiridoid components from Jasminum grandiflorum. Phytochemistry, 2007, 68(13), 1718-1721.
143. Vecchietti, V.; Ferrari, G.; Orsini, F.; Pelizzoni, F. Alkaloid and lignan constituents of Cinnamosma madagascariensis. Phytochemistry, 1979, 18(11), 1847-1849.
144. Key, J.; Scheuermann, T. H.; Anderson, P. C.; Daggett, V.; Gardner, K. H. Principles of ligand binding within a completely buried cavity in HIF2alpha PAS-B. J. Am. Chem. Soc., 2009, 131(48), 17647-17654.
145. Scheuermann, T. H.; Tomchick, D. R.; Machius, M.; Guo, Y.; Bruick, R. K.; Gardner, K. H. Artificial ligand binding within the HIF2alpha PAS-B domain of the HIF2 transcription factor. Proc. Natl. Acad. Sci. U. S. A., 2009, 106(2), 450-455.