Structure-Based Design of 1,4-Dibenzoylpiperazines as β-Catenin/B-Cell Lymphoma 9 Protein-Protein Interaction Inhibitors

ACS Medicinal Chemistry Letters

Volumn 7, Issue 5, 2016, Pages 508-513

  Wisniewski, John A ^a   Yin, Jinya ^a   Teuscher, Kevin B ^a   Zhang, Min ^a   Ji, Haitao ^a  

^a UNIVERSITY OF UTAH   (United States)

Author keywords

B cell lymphoma 9; inhibitor; protein protein interactions; selectivity; Wnt signaling; Catenin

Indexed keywords

ANTINEOPLASTIC AGENT; BETA CATENIN; CADHERIN; PIPERAZINE DERIVATIVE; PROTEIN; PROTEIN BCL 9; UNCLASSIFIED DRUG;

ARTICLE; BINDING SITE; CANCER INHIBITION; CELL VIABILITY ASSAY; COLORECTAL CANCER CELL LINE; CONCENTRATION RESPONSE; DRUG DESIGN; DRUG PROTEIN BINDING; HUMAN; HUMAN CELL; HYDROGEN BOND; HYDROPHILICITY; HYDROPHOBICITY; KIDNEY CELL; MOLECULAR MIMICRY; PRIORITY JOURNAL; PROTEIN PROTEIN INTERACTION; PROTEIN STRUCTURE; SIGNAL TRANSDUCTION; SITE DIRECTED MUTAGENESIS; STRUCTURE ACTIVITY RELATION;

EID: 84969567869     PISSN: None     EISSN: 19485875     Source Type: Journal    
DOI: 10.1021/acsmedchemlett.5b00284     Document Type: Article

References (35)

1. Clevers, H.; Loh, K. M.; Nusse, R. Stem cell signaling. An integral program for tissue renewal and regeneration: Wnt signaling and stem cell control Science 2014, 346, 1248012 10.1126/science.1248012
2. Zeng, X.; Huang, H.; Tamai, K.; Zhang, X.; Harada, Y.; Yokota, C.; Almeida, K.; Wang, J.; Doble, B.; Woodgett, J.; Wynshaw-Boris, A.; Hsieh, J.-C.; He, X. Initiation of Wnt signaling: control of Wnt coreceptor Lrp6 phosphorylation/activation via frizzled, dishevelled and axin functions Development 2008, 135, 367-375 10.1242/dev.013540
3. Mosimann, C.; Hausmann, G.; Basler, K. β-Catenin hits chromatin: regulation of Wnt target gene activation Nat. Rev. Mol. Cell Biol. 2009, 10, 276-286 10.1038/nrm2654
4. Clevers, H.; Nusse, R. Wnt/β-catenin signaling and disease Cell 2012, 149, 1192-1205 10.1016/j.cell.2012.05.012
5. Anastas, J. N.; Moon, R. T. WNT signalling pathways as therapeutic targets in cancer Nat. Rev. Cancer 2013, 13, 11-26 10.1038/nrc3419
6. Singh, S. K.; Hawkins, C.; Clarke, I. D.; Squire, J. A.; Bayani, J.; Hide, T.; Henkelman, R. M.; Cusimano, M. D.; Dirks, P. B. Identification of human brain tumour initiating cells Nature 2004, 432, 396-401 10.1038/nature03128
7. OBrien, C. A.; Pollett, A.; Gallinger, S.; Dick, J. E. A human colon cancer cell capable of initiating tumour growth in immunodeficient mice Nature 2007, 445, 106-110 10.1038/nature05372
8. Ricci-Vitiani, L.; Lombardi, D. G.; Pilozzi, E.; Biffoni, M.; Todaro, M.; Peschle, C.; De Maria, R. Identification and expansion of human colon-cancer-initiating cells Nature 2007, 445, 111-115 10.1038/nature05384
9. Malanchi, I.; Peinado, H.; Kassen, D.; Hussenet, T.; Metzger, D.; Chambon, P.; Huber, M.; Hohl, D.; Cano, A.; Birchmeier, W.; Huelsken, J. Cutaneous cancer stem cell maintenance is dependent on β-catenin signalling Nature 2008, 452, 650-653 10.1038/nature06835
10. Yeung, J.; Esposito, M. T.; Gandillet, A.; Zeisig, B. B.; Griessinger, E.; Bonnet, D.; So, C. W. E. β-Catenin mediates the establishment and drug resistance of MLL leukemic stem cells Cancer Cell 2010, 18, 606-618 10.1016/j.ccr.2010.10.032
11. Chen, B.; Dodge, M. E.; Tang, W.; Lu, J.; Ma, Z.; Fan, C.-W.; Wei, S.; Hao, W.; Kilgore, J.; Williams, N. S.; Roth, M. G.; Amatruda, J. F.; Chen, C.; Lum, L. Small molecule-mediated disruption of Wnt-dependent signaling in tissue regeneration and cancer Nat. Chem. Biol. 2009, 5, 100-107 10.1038/nchembio.137
12. Wang, X.; Moon, J.; Dodge, M. E.; Pan, X.; Zhang, L.; Hanson, J. M.; Tuladhar, R.; Ma, Z.; Shi, H.; Williams, N. S.; Amatruda, J. F.; Carroll, T. J.; Lum, L.; Chen, C. The development of highly potent inhibitors for porcupine J. Med. Chem. 2013, 56, 2700-2704 10.1021/jm400159c
13. Liu, J.; Pan, S.; Hsieh, M. H.; Ng, N.; Sun, F.; Wang, T.; Kasibhatla, S.; Schuller, A. G.; Li, A. G.; Cheng, D.; Li, J.; Tompkins, C.; Pferdekamper, A.; Steffy, A.; Cheng, J.; Kowal, C.; Phung, V.; Guo, G.; Wang, Y.; Graham, M. P.; Flynn, S.; Brenner, J. C.; Li, C.; Villarroel, M. C.; Schultz, P. G.; Wu, X.; McNamara, P.; Sellers, W. R.; Petruzzelli, L.; Boral, A. L.; Seidel, H. M.; McLaughlin, M. E.; Che, J.; Carey, T. E.; Vanasse, G.; Harris, J. L. Targeting Wnt-driven cancer through the inhibition of Porcupine by LGK974 Proc. Natl. Acad. Sci. U. S. A. 2013, 110, 20224-20229 10.1073/pnas.1314239110
14. Huang, S.-M.; Mishina, Y. M.; Liu, S.; Cheung, A.; Stegmeier, F.; Michaud, G. A.; Charlat, O.; Wiellette, E.; Zhang, Y.; Wiessner, S.; Hild, M.; Shi, X.; Wilson, C. J.; Mickanin, C.; Myer, V.; Fazal, A.; Tomlinson, R.; Serluca, F.; Shao, W.; Cheng, H.; Shultz, M.; Rau, C.; Schirle, M.; Schlegl, J.; Ghidelli, S.; Fawell, S.; Lu, C.; Curtis, D.; Kirschner, M. W.; Lengauer, C.; Finan, P. M.; Tallarico, J. A.; Bouwmeester, T.; Porter, J. A.; Bauer, A.; Cong, F. Tankyrase inhibition stabilizes axin and antagonizes Wnt signalling Nature 2009, 461, 614-620 10.1038/nature08356
15. Dancey, J. E.; Bedard, P. L.; Onetto, N.; Hudson, T. J. The genetic basis for cancer treatment decisions Cell 2012, 148, 409-420 10.1016/j.cell.2012.01.014
16. Emami, K. H.; Nguyen, C.; Ma, H.; Kim, D. H.; Jeong, K. W.; Eguchi, M.; Moon, R. T.; Teo, J.-L.; Kim, H. Y.; Moon, S. H.; Ha, J. R.; Kahn, M. A small molecule inhibitor of β-catenin/CREB-binding protein transcription Proc. Natl. Acad. Sci. U. S. A. 2004, 101, 12682-12687 10.1073/pnas.0404875101
17. Grossmann, T. N.; Yeh, J. T.-H.; Bowman, B. R.; Chu, Q.; Moellering, R. E.; Verdine, G. L. Inhibition of oncogenic Wnt signaling through direct targeting of β-catenin Proc. Natl. Acad. Sci. U. S. A. 2012, 109, 17942-17947 10.1073/pnas.1208396109
18. 17 binding site to selectively disrupt β-catenin/T-cell factor protein-protein interactions ACS Chem. Biol. 2014, 9, 193-201 10.1021/cb400795x
19. Brembeck, F. H.; Wiese, M.; Zatula, N.; Grigoryan, T.; Dai, Y.; Fritzmann, J.; Birchmeier, W. BCL9-2 promotes early stages of intestinal tumor progression Gastroenterology 2011, 141, 1359-1370 10.1053/j.gastro.2011.06.039
20. Deka, J.; Wiedemann, N.; Anderle, P.; Murphy-Seiler, F.; Bultinck, J.; Eyckerman, S.; Stehle, J.-C.; André, S.; Vilain, N.; Zilian, O.; Robine, S.; Delorenzi, M.; Basler, K.; Aguet, M. Bcl9/Bcl9l are critical for Wnt-mediated regulation of stem cell traits in colon epithelium and adenocarcinomas Cancer Res. 2010, 70, 6619-6628 10.1158/0008-5472.CAN-10-0148
21. Adachi, S.; Jigami, T.; Yasui, T.; Nakano, T.; Ohwada, S.; Omori, Y.; Sugano, S.; Ohkawara, B.; Shibuya, H.; Nakamura, T.; Akiyama, T. Role of a BCL9-related β-catenin-binding protein, B9L, in tumorigenesis induced by aberrant activation of Wnt signaling Cancer Res. 2004, 64, 8496-8501 10.1158/0008-5472.CAN-04-2254
22. Brembeck, F. H.; Schwarz-Romond, T.; Bakkers, J.; Wilhelm, S.; Hammerschmidt, M.; Birchmeier, W. Essential role of BCL9-2 in the switch between β-catenins adhesive and transcriptional functions Genes Dev. 2004, 18, 2225-2230 10.1101/gad.317604
23. de la Roche, M.; Worm, J.; Bienz, M. The function of BCL9 in Wnt/β-catenin signaling and colorectal cancer cells BMC Cancer 2008, 8, 199 10.1186/1471-2407-8-199
24. Mani, M.; Carrasco, D. E.; Zhang, Y.; Takada, K.; Gatt, M. E.; Dutta-Simmons, J.; Ikeda, H.; Diaz-Griffero, F.; Pena-Cruz, V.; Bertagnolli, M.; Myeroff, L. L.; Markowitz, S. D.; Anderson, K. C.; Carrasco, D. R. BCL9 promotes tumor progression by conferring enhanced proliferative, metastatic, and angiogenic properties to cancer cells Cancer Res. 2009, 69, 7577-7586 10.1158/0008-5472.CAN-09-0773
25. Elsarraj, H. S.; Hong, Y.; Valdez, K. E.; Michaels, W.; Hook, M.; Smith, W. P.; Chien, J.; Herschkowitz, J. I.; Troester, M. A.; Beck, M.; Inciardi, M.; Gatewood, J.; May, L.; Cusick, T.; McGinness, M.; Ricci, L.; Fan, F.; Tawfik, O.; Marks, J. R.; Knapp, J. R.; Yeh, H.-W.; Thomas, P.; Carrasco, D. R.; Fields, T. A.; Godwin, A. K.; Behbod, F. Expression profiling of in vivo ductal carcinoma in situ progression models identified B cell lymphoma-9 as a molecular driver of breast cancer invasion Breast Cancer Res. 2015, 17, 128 10.1186/s13058-015-0630-z
26. Moor, A. E.; Anderle, P.; Cantù, C.; Rodriguez, P.; Wiedemann, N.; Baruthio, F.; Deka, J.; André, S.; Valenta, T.; Moor, M. B.; Gyorffy, B.; Barras, D.; Delorenzi, M.; Basler, K.; Aguet, M. BCL9/9L-β-catenin signaling is associated with poor outcome in colorectal cancer EBioMedicine 2015, 2, 1932-1943 10.1016/j.ebiom.2015.10.030
27. Sampietro, J.; Dahlberg, C. L.; Cho, U. S.; Hinds, T. R.; Kimelman, D.; Xu, W. Crystal structure of a β-catenin/BCL9/Tcf4 complex Mol. Cell 2006, 24, 293-300 10.1016/j.molcel.2006.09.001
28. Kawamoto, S. A.; Thompson, A. D.; Coleska, A.; Nikolovska-Coleska, Z.; Yi, H.; Wang, S. Analysis of the interaction of BCL9 with beta-catenin and development of fluorescence polarization and surface plasmon resonance binding assays for this interaction Biochemistry 2009, 48, 9534-9541 10.1021/bi900770z
29. Zhang, M.; Wisniewski, J. A.; Ji, H. AlphaScreen selectivity assay for β-catenin/B-cell lymphoma 9 inhibitors Anal. Biochem. 2015, 469, 43-53 10.1016/j.ab.2014.09.018
30. de la Roche, M.; Rutherford, T. J.; Gupta, D.; Veprintsev, D. B.; Saxty, B.; Freund, S. M.; Bienz, M. An intrinsically labile α-helix abutting the BCL9-binding site of β-catenin is required for its inhibition by carnosic acid Nat. Commun. 2012, 3, 680 10.1038/ncomms1680
31. Kawamoto, S. A.; Coleska, A.; Ran, X.; Yi, H.; Yang, C.-Y.; Wang, S. Design of triazole-stapled BCL9 α-helical peptides to target the β-catenin/B-cell CLL/lymphoma 9 (BCL9) protein-protein interaction J. Med. Chem. 2012, 55, 1137-1146 10.1021/jm201125d
32. Takada, K.; Zhu, D.; Bird, G. H.; Sukhdeo, K.; Zhao, J.-J.; Mani, M.; Lemieux, M.; Carrasco, D. E.; Ryan, J.; Horst, D.; Fulciniti, M.; Munshi, N. C.; Xu, W.; Kung, A. L.; Shivdasani, R. A.; Walensky, L. D.; Carrasco, D. R. Targeted disruption of the BCL9/β-catenin complex inhibits oncogenic Wnt signaling Sci. Transl. Med. 2012, 4, 148ra117 10.1126/scitranslmed.3003808
33. Zhao, J.-J.; Lin, J.; Zhu, D.; Wang, X.; Brooks, D.; Chen, M.; Chu, Z.-B.; Takada, K.; Ciccarelli, B.; Admin, S.; Tao, J.; Tai, Y.-T.; Treon, S.; Pinkus, G.; Kuo, W. P.; Hideshima, T.; Bouxsein, M.; Munshi, N.; Anderson, K.; Carrasco, R. miR-30-5p functions as a tumor suppressor and novel therapeutic tool by targeting the oncogenic Wnt/β-catenin/BCL9 pathway Cancer Res. 2014, 74, 1801-1813 10.1158/0008-5472.CAN-13-3311-T
34. Hoggard, L. R.; Zhang, Y.; Zhang, M.; Panic, V.; Wisniewski, J. A.; Ji, H. Rational design of selective small-molecule inhibitors for catenin/B-cell lymphoma 9 protein-protein interactions J. Am. Chem. Soc. 2015, 137, 12249-12260 10.1021/jacs.5b04988
35. Halgren, T. A. Identifying and characterizing binding sites and assessing druggability J. Chem. Inf. Model. 2009, 49, 377-389 10.1021/ci800324m