Discovery of novel STAT3 small molecule inhibitors via in silico site-directed fragment-based drug design

Journal of Medicinal Chemistry

Volumn 56, Issue 11, 2013, Pages 4402-4412

  Yu, Wenying ^a   Xiao, Hui ^a   Lin, Jiayuh ^a   Li, Chenglong ^a  

^a OHIO STATE UNIVERSITY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

5,8 DIOXO 6 (PYRIDIN 3 YLAMINO) 5,8 DIHYDRONAPHTHALENE 1 SULFONAMIDE; INTERLEUKIN 6; PHOSPHOTYROSINE; PROTEIN INHIBITOR OF ACTIVATED STAT; PROTEIN SH2; STAT3 PROTEIN; UNCLASSIFIED DRUG;

ANIMAL EXPERIMENT; APOPTOSIS; ARTICLE; BINDING AFFINITY; BINDING SITE; CANCER CELL; CANCER CELL CULTURE; CANCER INHIBITION; COMPUTER MODEL; CONTROLLED STUDY; DRUG ACTIVITY; DRUG DESIGN; DRUG SYNTHESIS; FLUORESCENCE POLARIZATION; HUMAN; HUMAN CELL; IC 50; IN VIVO STUDY; MOUSE; NONHUMAN; PROTEIN PHOSPHORYLATION;

AMINOPYRIDINES; ANIMALS; ANTINEOPLASTIC AGENTS; APOPTOSIS; CELL LINE, TUMOR; CELL SURVIVAL; COMPUTER SIMULATION; DRUG DESIGN; DRUG SCREENING ASSAYS, ANTITUMOR; FLUORESCENCE POLARIZATION; HUMANS; MICE; MICE, NUDE; MODELS, MOLECULAR; NEOPLASM TRANSPLANTATION; PHOSPHORYLATION; PROTEIN BINDING; PROTEIN MULTIMERIZATION; SMALL MOLECULE LIBRARIES; SRC HOMOLOGY DOMAINS; STAT3 TRANSCRIPTION FACTOR; STRUCTURE-ACTIVITY RELATIONSHIP; SULFONAMIDES; TRANSPLANTATION, HETEROLOGOUS; TUMOR BURDEN;

EID: 84879056436     PISSN: 00222623     EISSN: 15204804     Source Type: Journal    
DOI: 10.1021/jm400080c     Document Type: Article

References (24)

1. Mandal, P. K.; Gao, F.; Lu, Z.; Ren, Z.; Ramesh, R.; Birtwistle, J. S.; Kaluarachchi, K. K.; Chen, X.; Bast, R. C.; Liao, W. S.; McMurray, J. S. Potent and Selective Phosphopeptide Mimetic Prodrugs Targeted to the Src Homology 2 (SH2) Domain of Signal Transducer and Activator of Transcription 3 J. Med. Chem. 2011, 54, 3549-3563
2. Mandal, P. K.; Ren, Z. Y.; Chen, X. M.; Xiong, C. Y.; McMurray, J. S. Structure-Affinity Relationships of Glutamine Mimics Incorporated into Phosphopeptides Targeted to the SH2 Domain of Signal Transducer and Activator of Transcription 3 J. Med. Chem. 2009, 52, 6126-6141
3. Liu, A.; Liu, Y.; Xu, Z.; Yu, W.; Wang, H.; Li, C.; Lin, J. Novel small molecule, XZH-5, inhibits constitutive and interleukin-6-induced STAT3 phosphorylation in human rhabdomyosarcoma cells Cancer Sci. 2011, 102, 1381-1387
4. Liu, Y.; Liu, A.; Xu, Z.; Yu, W.; Wang, H.; Li, C.; Lin, J. XZH-5 inhibits STAT3 phosphorylation and causes apoptosis in human hepatocellular carcinoma cells Apoptosis 2011, 16, 502-510
5. Song, H.; Wang, R.; Wang, S.; Lin, J.; Stark, G. R. A Low-Molecular-Weight Compound Discovered through Virtual Database Screening Inhibits Stat3 Function in Breast Cancer Cells Proc. Natl. Acad. Sci. U. S. A. 2005, 102, 4700-4705 (Pubitemid 40471517)
6. Schust, J.; Sperl, B.; Hollis, A.; Mayer, T. U.; Berg, T. Stattic: a small-molecule inhibitor of STAT3 activation and dimerization Chem. Biol. 2006, 13, 1235-1242 (Pubitemid 44750735)
7. Lin, L.; Hutzen, B.; Li, P.-K.; Ball, S.; Zuo, M.; DeAngelis, S.; Foust, E.; Sobo, M.; Friedman, L.; Bhasin, D.; Cen, L.; Li, C.; Lin, J. A novel small molecule, LLL12, inhibits STAT3 phosphorylation and activities and exhibits potent growth suppressive activity in human cancer cells Neoplasia 2010, 12, 39-50
8. Hajduk, P. J.; Greer, J. A decade of fragment-based drug design: strategic advances and lessons learned Nature Rev. Drug Discovery 2007, 6, 211-219 (Pubitemid 46344625)
9. Chen, Y.; Shoichet, B. K. Molecular docking and ligand specificity in fragment-based inhibitor discovery Nature Chem. Biol. 2009, 5, 358-364
10. Lima, L. M.; Barreiro, E. J. Bioisosterism: a useful strategy for molecular modification and drug design Curr. Med. Chem. 2005, 12, 23-49 (Pubitemid 40089827)
11. Bhasin, D.; Cisek, K.; Pandharkar, T.; Regan, N.; Li, C. L.; Pandit, B.; Lin, J.; Li, P. K. Design, synthesis, and studies of small molecule STAT3 inhibitors Bioorg. Med. Chem. Lett. 2008, 18, 391-395
12. Matsuno, K.; Masuda, Y.; Uehara, Y.; Sato, H.; Muroya, A.; Takahashi, O.; Yokotagawa, T.; Furuya, T.; Okawara, T.; Otsuka, M.; Ogo, N.; Ashizawa, T.; Oshita, C.; Tai, S.; Ishii, H.; Akiyama, Y.; Asai, A. Identification of a New Series of STAT3 Inhibitors by Virtual Screening ACS Med. Chem. Lett. 2010, 1, 371-375
13. Turkson, J.; Kim, J. S.; Zhang, S. M.; Yuan, J.; Huang, M.; Glenn, M.; Haura, E.; Sebti, S.; Hamilton, A. D.; Jove, R. Novel peptidomimetic inhibitors of signal transducer and activator of transcription 3 dimerization and biological activity Mol. Cancer Ther. 2004, 3, 261-269 (Pubitemid 39193701)
14. Ren, X. M.; Duan, L.; He, Q. A.; Zhang, Z.; Zhou, Y.; Wu, D. H.; Pan, J. X.; Pei, D. Q.; Ding, K. Identification of Niclosamide as a New Small-Molecule Inhibitor of the STAT3 Signaling Pathway. ACS Med. Chem. Lett. 1, 454-459.
15. Siddiquee, K. A. Z.; Gunning, P. T.; Glenn, M.; Katt, W. P.; Zhang, S.; Schroeck, C.; Sebti, S. M.; Jove, R.; Hamilton, A. D.; Turkson, J. An oxazole-based small-molecule Stat3 inhibitor modulates Stat3 stability and processing and induces antitumor cell effects ACS Chem. Biol. 2007, 2, 787-798 (Pubitemid 351166054)
16. Faruqi, T. R.; Gomez, D.; Bustelo, X. R.; Bar-Sagi, D.; Reich, N. C. Rac1 mediates STAT3 activation by autocrine IL-6 Proc. Natl. Acad. Sci. U. S. A. 2001, 98, 9014-9019 (Pubitemid 32743861)
17. Yu, H.; Pardoll, D.; Jove, R. STATs in cancer inflammation and immunity: a leading role for STAT3 Nature Rev. Cancer 2009, 9, 798-809
18. Viegas-Junior, C.; Danuello, A.; Bolzani, V. S.; Barreiro, E. J.; Fraga, C. A. M. Molecular hybridization: a useful tool in the design of new drug prototypes Curr. Med. Chem. 2007, 14, 1829-1852 (Pubitemid 47163402)
19. Huey, R.; Morris, G. M.; Olson, A. J.; Goodsell, D. S. A semiempirical free energy force field with charge-based desolvation J. Comput. Chem. 2007, 28, 1145-1152 (Pubitemid 46506716)
20. 2012: LigPrep Suite 2012, version 2.5; Schrödinger, LLC, New York, 2012.
21. Schrödinger Suite 2011 Protein Preparation Wizard; Schrödinger, LLC, New York, 2012
22. Epik, version 2.3; Schrödinger, LLC: New York, 2012
23. Impact, version 5.8; Schrödinger, LLC: New York, 2012
24. Prime, version 3.1; Schrödinger, LLC: New York, 2012.