A R T I C L E
N AT URE CO M MU N ICAT IO N S | D O I: 10 . 10 38/ s414 67 -01 8- 063 15 - w
References
32. Salome, C. et al. Benzofuran derivatives as anticancer inhibitors of mTOR
signaling. Eur. J. Med. Chem. 81, 181–191 (2014).
1.
Burge, S., Parkinson, G. N., Hazel, P., Todd, A. K. & Neidle, S. Quadruplex
DNA: sequence, topology and structure. Nucleic Acids Res. 34, 5402–5415
33. Simmons, J. K. et al. Cooperative targets of combined mTOR/HDAC
inhibition promote MYC degradation. Mol. Cancer Ther. 16, 2008–2021
(2017).
(
2006).
2.
3.
4.
5.
6.
7.
Bacolla, A. & Wells, R. D. Non-B DNA conformations, genomic
rearrangements, and human disease. J. Biol. Chem. 279, 47411–47414 (2004).
Neidle, S. Quadruplex nucleic acids as novel therapeutic targets. J. Med. Chem.
34. Chatterjee, J., Mierke, D. F. & Kessler, H. Conformational preference and
potential templates of N-methylated cyclic pentaalanine peptides. Chem. Eur.
J. 14, 1508–1517 (2008).
35. Agrawal, P., Lin, C., Mathad, R. I., Carver, M. & Yang, D. Z. The major G-
quadruplex formed in the human BCL-2 proximal promoter adopts a parallel
structure with a 13-nt loop in K+solution. J. Am. Chem. Soc. 136, 1750–1753
(2014).
36. Agrawal, P., Hatzakis, E., Guo, K. X., Carver, M. & Yang, D. Z. Solution
structure of the major G-quadruplex formed in the human VEGF promoter in
K+: insights into loop interactions of the parallel G-quadruplexes. Nucleic
Acids Res. 41, 10584–10592 (2013).
5
9, 5987–6011 (2016).
Neidle, S. Quadruplex nucleic acids as targets for anticancer therapeutics. Nat.
Rev. Chem. 1, 0041 (2017).
Thomas, J. R. & Hergenrother, P. J. Targeting RNA with small molecules.
Chem. Rev. 108, 1171–1224 (2008).
Ali, A. & Bhattacharya, S. DNA binders in clinical trials and chemotherapy.
Bioorgan. Med. Chem. 22, 4506–4521 (2014).
Gregory, M. A. & Hann, S. R. c-Myc proteolysis by the ubiquitin-proteasome
pathway: Stabilization of c-Myc in Burkitt’s lymphoma cells. Mol. Cell Biol. 20,
2
423–2435 (2000).
37. Brito, H. et al. Targeting KRAS oncogene in colon cancer cells with 7-
carboxylate indolo[3,2-b]quinoline tri-alkylamine derivatives. PLoS ONE 10,
e0126891 (2015).
8
.
.
Whitfield, J. R., Beaulieu, M. E. & Soucek, L. Strategies to inhibit Myc and their
clinical applicability. Front. Cell Dev. Biol. 5, 10 (2017).
9
Bretones, G., Delgado, M. D. & Leon, J. Myc and cell cycle control. Biochim
Biophys Acta 1849, 506–516 (2015).
0. Dang, C. V. MYC on the path to cancer. Cell 149, 22–35 (2012).
1. Lin, C. Y. et al. Transcriptional amplification in tumor cells with elevated c-
Myc. Cell 151, 56–67 (2012).
2. Nie, Z. Q. et al. c-Myc is a universal amplifier of expressed genes in
lymphocytes and embryonic stem cells. Cell 151, 68–79 (2012).
3. Cui, J. J., Waltman, P., Le, V. H. & Lewis, E. A. The effect of molecular
crowding on the stability of human c-MYC promoter sequence I-motif at
neutral pH. Molecules 18, 12751–12767 (2013).
38. Palumbo, S. L. et al. A novel G-quadruplex-forming GGA repeat region in the
c-myb promoter is a critical regulator of promoter activity. Nucleic Acids Res.
36, 1755–1769 (2008).
39. De Armond, R., Wood, S., Sun, D., Hurley, L. H. & Ebbinghaus, S. W.
Evidence for the presence of a guanine quadruplex forming region within a
polypurine tract of the hypoxia inducible factor 1alpha promoter.
Biochemistry 44, 16341–16350 (2005).
40. Moye, A. L. et al. Telomeric G-quadruplexes are a substrate and site of
localization for human telomerase. Nat. Commun. 6, 7643 (2015).
41. Yoshida, W., Saito, T., Yokoyama, T., Ferri, S. & Ikebukuro, K. Aptamer
selection based on G4-forming promoter region. PLoS ONE 8, e65497 (2013).
42. Kumari, S., Bugaut, A., Huppert, J. L. & Balasubramanian, S. An RNA G-
quadruplex in the 5 ‘ UTR of the NRAS proto-oncogene modulates
translation. Nat. Chem. Biol. 3, 218–221 (2007).
1
1
1
1
1
1
1
1
1
1
2
4. Zhang, L. et al. The impact of C-MYC gene expression on gastric cancer cell.
Mol. Cell Biochem. 344, 125–135 (2010).
5. Dang, C. V., Reddy, E. P., Shokat, K. M. & Soucek, L. Drugging the
‘
undruggable’ cancer targets. Nat. Rev. Cancer 17, 502–508 (2017).
6. Rhodes, D. & Lipps, H. J. G-quadruplexes and their regulatory roles in
biology. Nucleic Acids Res. 43, 8627–8637 (2015).
7. Nasiri, H. R. et al. Targeting a c-MYC G-quadruplex DNA with a fragment
library. Chem. Commun. (Camb.). 50, 1704–1707 (2014).
8. Ohnmacht, S. A. & Neidle, S. Small-molecule quadruplex-targeted drug
discovery. Bioorg. Med. Chem. Lett. 24, 2602–2612 (2014).
9. Hansel-Hertsch, R. et al. G-quadruplex structures mark human regulatory
chromatin. Nat. Genet. 48, 1267–1272 (2016).
0. Kwok, C. K., Marsico, G., Sahakyan, A. B., Chambers, V. S. &
Balasubramanian, S. rG4-seq reveals widespread formation of G-quadruplex
structures in the human transcriptome. Nat. Methods 13, 841 (2016).
1. Chambers, V. S. et al. High-throughput sequencing of DNA G-quadruplex
structures in the human genome. Nat. Biotechnol. 33, 877 (2015).
2. Deng, N., Wickstrom, L., Cieplak, P., Lin, C. & Yang, D. Resolving the ligand-
binding specificity in c-MYC G-quadruplex DNA: absolute binding free
energy calculations and SPR experiment. J. Phys. Chem. B 121, 10484–10497
43. Brown, R. V., Danford, F. L., Gokhale, V., Hurley, L. H. & Brooks, T. A.
Demonstration that drug-targeted down-regulation of MYC in non-hodgkins
lymphoma is directly mediated through the promoter G-quadruplex. J. Biol.
Chem. 286, 41018–41027 (2011).
44. Onel, B. et al. A new G-quadruplex with hairpin loop immediately upstream
of the human BCL2 P1 promoter modulates transcription. J. Am. Chem. Soc.
138, 2563–2570 (2016).
45. Burger, A. M. et al. The G-quadruplex-interactive molecule BRACO-19
inhibits tumor growth, consistent with telomere targeting and interference
with telomerase function. Cancer Res. 65, 1489–1496 (2005).
46. Huang, R., Bonnichon, A., Claridge, T. D. W. & Leung, I. K. H. Protein-ligand
binding affinity determination by the waterLOGSY method: an optimised
approach considering ligand rebinding. Sci. Rep. 7, 43727 (2017).
47. Szczepina, M. G., Bleile, D. W., Mullegger, J., Lewis, A. R. & Pinto, B. M.
WaterLOGSY NMR experiments in conjunction with molecular-dynamics
simulations identify immobilized water molecules that bridge peptide mimic
MDWNMHAA to anticarbohydrate antibody SYA/J6. Chemistry 17,
11438–11445 (2011).
48. Thordarson, P. Determining association constants from titration experiments
in supramolecular chemistry. Chem. Soc. Rev. 40, 1305–1323 (2011).
49. Kim, D. et al. (2R)-4-Oxo-4-[3-(trifluoromethyl)-5,6-dihydro[1,2,4]triazolo
[4,3-alpha]pyrazin-7(8H)-yl]-1-(2,4,5-trifluorophenyl)butan-2-amine: a
potent, orally active dipeptidyl peptidase IV inhibitor for the treatment of type
2 diabetes. J. Med. Chem. 48, 141–151 (2005).
2
2
(
2017).
2
3. Tomonaga, T. & Levens, D. Activating transcription from single stranded
DNA. Proc. Natl Acad. Sci. USA 93, 5830–5835 (1996).
4. Boddupally, P. V. et al. Anticancer activity and cellular repression of c-MYC
by the G-quadruplex-stabilizing 11-piperazinylquindoline is not dependent on
direct targeting of the G-quadruplex in the c-MYC promoter. J. Med. Chem.
2
5
5, 6076–6086 (2012).
2
5. Ambrus, A., Chen, D., Dai, J. X., Jones, R. A. & Yang, D. Z. Solution structure
of the biologically relevant g-quadruplex element in the human c-MYC
promoter. implications for g-quadruplex stabilization. Biochemistry 44,
50. Weisberg, E. et al. Characterization of AMN107, a selective inhibitor of native
and mutant Bcr-Abl. Cancer Cell. 7, 129–141 (2005).
2
048–2058 (2005).
51. Fraley, M. E. et al. Kinesin spindle protein (KSP) inhibitors. Part 2: The
design, synthesis, and characterization of 2,4-diaryl-2,5-dihydropyrrole
inhibitors of the mitotic kinesin KSP. Bioorg. Med. Chem. Lett. 16, 1775–1779
(2006).
52. Bissantz, C., Kuhn, B. & Stahl, M. A medicinal chemist’s guide to molecular
interactions. J. Med. Chem. 53, 5061–5084 (2010).
2
6. Dai, J. X., Carver, M., Hurley, L. H. & Yang, D. Z. Solution structure of a 2:1
quindoline-c-MYC G-quadruplex: insights into G-quadruplex-interactive
small molecule drug design. J. Am. Chem. Soc. 133, 17673–17680 (2011).
7. Balasubramanian, S., Hurley, L. H. & Neidle, S. Targeting G-quadruplexes in
gene promoters: a novel anticancer strategy? Nat. Rev. Drug Discov. 10,
2
2
61–275 (2011).
53. Gallivan, J. P. & Dougherty, D. A. Cation-pi interactions in structural biology.
Proc. Natl Acad. Sci. USA 96, 9459–9464 (1999).
54. Mathad, R. I., Hatzakis, E., Dai, J. X. & Yang, D. Z. c-MYC promoter G-
quadruplex formed at the 5 ‘-end of NHE III1 element: insights into biological
relevance and parallel-stranded G-quadruplex stability. Nucleic Acids Res. 39,
9023–9033 (2011).
2
2
8. Xu, H. et al. CX-5461 is a DNA G-quadruplex stabilizer with selective lethality
in BRCA1/2 deficient tumours. Nat. Commun. 8, 14432 (2017).
9. Bidzinska, J., Cimino-Reale, G., Zaffaroni, N. & Folini, M. G-quadruplex
structures in the human genome as novel therapeutic targets. Molecules 18,
12368–12395 (2013).
3
0. Felsenstein, K. M. et al. Small molecule microarrays enable the identification
of a selective, quadruplex-binding inhibitor of MYC expression. ACS Chem.
Biol. 11, 139–148 (2016).
55. Micco, M. et al. Structure-based design and evaluation of naphthalene diimide
G-quadruplex ligands as telomere targeting agents in pancreatic cancer cells. J.
Med. Chem. 56, 2959–2974 (2013).
3
1. Xia, L. & Lee, Y. R. Regioselective synthesis of novel and diverse naphtho[1,2-
b]furan-3-carboxamides and benzofuran-3-carboxamides by cascade formal
56. Chung, W. J. et al. Solution structure of an intramolecular (3+1) human
telomeric G-quadruplex bound to a telomestatin derivative. J. Am. Chem. Soc.
135, 13495–13501 (2013).
[
3+2] cycloaddition. RSC Adv. 4, 36905–36916 (2014).
1
4
N A TU RE CO MMUN I C A TI O N S | ( 2 0 1 8) 9: 4 2 2 9 | D OI : 1 0 . 1 0 3 8/ s 4 1 46 7 - 0 1 8- 0 63 1 5 - w | w ww . na tu r e . c o m /n atu r e c o m m u n ic ati o n s