Improving the affinity of SL0101 for RSK using structure-based design

ACS Medicinal Chemistry Letters

Volumn 4, Issue 2, 2013, Pages 175-179

  Mrozowski, Roman M ^a   Vemula, Rajender ^b   Wu, Bulan ^c   Zhang, Qi ^b   Schroeder, Benjamin R ^d   Hilinski, Michael K ^e   Clark, David E ^e   Hecht, Sidney M ^f   O'Doherty, George A ^b   Lannigan, Deborah A ^a  

^a VANDERBILT UNIVERSITY   (United States)

^b NORTHEASTERN UNIVERSITY   (United States)

^c WEST VIRGINIA UNIVERSITY   (United States)

^d Oratory Preparatory School   (United States)

^e UNIVERSITY OF VIRGINIA   (United States)

^f ARIZONA STATE UNIVERSITY   (United States)

Author keywords

Kaempferol 3 O (3 ,4 di O acetyl l rhamnopyranoside); kinase inhibitor; p90 ribosomal S6 kinase; RSK; SL0101

Indexed keywords

KAEMPFEROL DERIVATIVE; SL 0101; SL0101; UNCLASSIFIED DRUG;

ACYLATION; ARTICLE; BREAST CANCER; CELL PROLIFERATION; CRYSTAL STRUCTURE; DIHYDROXYLATION; DRUG BINDING SITE; DRUG HALF LIFE; DRUG PROTEIN BINDING; GLYCOSYLATION; HYDROGEN BOND; HYDROGENOLYSIS; IN VITRO STUDY; IN VIVO STUDY; MEMBRANE PERMEABILITY; PRIORITY JOURNAL; PROTEIN PHOSPHORYLATION;

EID: 84873942644     PISSN: None     EISSN: 19485875     Source Type: Journal    
DOI: 10.1021/ml300298v     Document Type: Article

References (31)

1. Eisinger-Mathason, T. S.; Andrade, J.; Lannigan, D. A. RSK in tumorigenesis: connections to steroid signaling Steroids 2010, 75 (3) 191-202
2. Clark, D. E.; Errington, T. M.; Smith, J. A.; Frierson, H. F., Jr.; Weber, M. J.; Lannigan, D. A. The serine/threonine protein kinase, p90 ribosomal S6 kinase, is an important regulator of prostate cancer cell proliferation Cancer Res. 2005, 65 (8) 3108-3116
3. Lara, R.; Mauri, F. A.; Taylor, H.; Derua, R.; Shia, A.; Gray, C.; Nicols, A.; Shiner, R. J.; Schofield, E.; Bates, P. A.; Waelkens, E.; Dallman, M.; Lamb, J.; Zicha, D.; Downward, J.; Seckl, M. J.; Pardo, O. E. An siRNA screen identifies RSK1 as a key modulator of lung cancer metastasis Oncogene 2011, 30 (32) 3513-3521
4. Anjum, R.; Blenis, J. The RSK family of kinases: emerging roles in cellular signalling Nat. Rev. Mol. Cell Biol. 2008, 9 (10) 747-758
5. Smith, J. A.; Poteet-Smith, C. E.; Xu, Y.; Errington, T. M.; Hecht, S. M.; Lannigan, D. A. Identification of the first specific inhibitor of p90 ribosomal S6 kinase (RSK) reveals an unexpected role for RSK in cancer cell proliferation Cancer Res. 2005, 65 (3) 1027-1034
6. Doehn, U.; Hauge, C.; Frank, S. R.; Jensen, C. J.; Duda, K.; Nielsen, J. V.; Cohen, M. S.; Johansen, J. V.; Winther, B. R.; Lund, L. R.; Winther, O.; Taunton, J.; Hansen, S. H.; Frodin, M. RSK is a principal effector of the RAS-ERK pathway for eliciting a coordinate promotile/invasive gene program and phenotype in epithelial cells Mol. Cell 2009, 35 (4) 511-522
7. Bain, J.; Plater, L.; Elliott, M.; Shpiro, N.; Hastie, C. J.; McLauchlan, H.; Klevernic, I.; Arthur, J. S.; Alessi, D. R.; Cohen, P. The selectivity of protein kinase inhibitors: a further update Biochem. J. 2007, 408 (3) 297-315
8. Utepbergenov, D.; Derewenda, U.; Olekhnovich, N.; Szukalska, G.; Banerjee, B.; Hilinski, M. K.; Lannigan, D. A.; Stukenberg, P. T.; Derewenda, Z. S. Insights into the inhibition of the p90 ribosomal S6 kinase (RSK) by the flavonol glycoside SL0101 from the 1.5 Å crystal structure of the N-terminal domain of RSK2 with bound inhibitor Biochemistry 2012, 51 (33) 6499-6510
9. Smith, J. A.; Maloney, D. J.; Hecht, S. M.; Lannigan, D. A. Structural basis for the activity of the RSK-specific inhibitor, SL0101 Bioorg. Med. Chem. 2007, 15 (14) 5018-5034
10. Hilinski, M. K.; Mrozowski, R. M.; Clark, D. E.; Lannigan, D. A. Analogs of the RSK inhibitor SL0101: optimization of in vitro biological stability Bioorg. Med. Chem. Lett. 2012, 22 (9) 3244-3247
11. Maloney, D. J.; Hecht, S. M. Synthesis of a potent and selective inhibitor of p90 RSK Org. Lett. 2005, 7 (6) 1097-1099
12. Shan, M.; Sharif, E. U.; O'Doherty, G. A. Total synthesis of jadomycin A and a carbasugar analogue of jadomycin B Angew. Chem., Int. Ed. 2010, 49 (49) 9492-9495
13. Borisova, S. A.; Guppi, S. R.; Kim, H. J.; Wu, B.; Penn, J. H.; Liu, H. W.; O'Doherty, G. A. A de novo approach to the synthesis of glycosylated methymycin analogues with structural and stereochemical diversity Org. Lett. 2010, 12 (22) 5150-5153
14. Shan, M.; O'Doherty, G. A. De novo asymmetric syntheses of SL0101 and its analogues via a palladium-catalyzed glycosylation Org. Lett. 2006, 8 (22) 5149-5152
15. Shan, M.; O'Doherty, G. A. Synthesis of SL0101 carbasugar analogues: carbasugars via Pd-catalyzed cyclitolization and post-cyclitolization transformations Org. Lett. 2010, 12 (13) 2986-2989
16. Wang, H. Y.; Wu, B.; Qi, Z.; Kang, S. W.; Rojanasakul, Y.; O'Doherty, G. A. C5′-alkyl substitution effects on digitoxigenin α-L-glycoside cancer cytotoxicity ACS Med. Chem. Lett. 2011, 2 (4) 259-263
17. Wang, H. Y.; Rojanasakul, Y.; O'Doherty, G. A. Synthesis and evaluation of the α-D-/α-L-rhamnosyl and amicetosyl digitoxigenin oligomers as anti-tumor agents ACS Med. Chem. Lett. 2011, 2 (4) 264-269
18. Wang, H. Y.; Xin, W.; Zhou, M.; Stueckle, T. A.; Rojanasakul, Y.; O'Doherty, G. A. Stereochemical survey of digitoxin monosaccharides: new anticancer analogues with enhanced apoptotic activity and growth inhibitory effect on human non-small cell lung cancer cell ACS Med. Chem. Lett. 2011, 2 (1) 73-78
19. Iyer, A. K.; Zhou, M.; Azad, N.; Elbaz, H.; Wang, L.; Rogalsky, D. K.; Rojanasakul, Y.; O'Doherty, G. A.; Langenhan, J. M. A direct comparison of the anticancer activities of digitoxin MeON-neoglycosides and O-glycosides: oligosaccharide chain length-dependent induction of caspase-9-mediated apoptosis ACS Med. Chem. Lett. 2010, 1 (7) 326-330
20. Zhou, M.; O'Doherty, G. The de novo synthesis of oligosaccharides: application to the medicinal chemistry SAR-study of digitoxin Curr. Top. Med. Chem. 2008, 8 (2) 114-125
21. Babu, R. S.; O'Doherty, G. A. Palladium-catalyzed glycosylation reaction: de-novo synthesis of trehalose analogues J. Carbohydr. Chem. 2005, 24 (2) 169-177
22. Wu, B.; Li, M.; O'Doherty, G. A. Synthesis of several cleistrioside and cleistetroside natural products via a divergent de novo asymmetric approach Org. Lett. 2010, 12 (23) 5466-5469
23. Harris, J. M.; Keranen, M. D.; Nguyen, H.; Young, V. G.; O'Doherty, G. A. Syntheses of four D- and L-hexoses via diastereoselective and enantioselective dihydroxylation reactions Carbohydr. Res. 2000, 328 (1) 17-36
24. Li, M.; Scott, J. G.; O'Doherty, G. A. Synthesis of 7-oxa-phomopsolide E and its C-4 epimer Tetrahedron Lett. 2004, 45 (5) 1005-1009
25. Luche, J. L. Lanthanides in organic chemistry. 1. Selective 1,2 reductions of conjugated ketones J. Am. Chem. Soc. 1978, 100 (7) 2226-2227
26. Luche, J.-L.; Rodriguez-Hahn, L.; Crabbe, P. Reduction of natural enones in the presence of cerium trichloride J. Chem. Soc., Chem. Commun. 1978, 14, 601-602
27. Gemal, A. L.; Luche, J. L. Lanthanoids in organic synthesis. 6. Reduction of α-enones by sodium borohydride in the presence of lanthanoid chlorides: synthetic and mechanistic aspects J. Am. Chem. Soc. 1981, 103 (18) 5454-5459
28. 4 oxidation of olefins to cis -1,2-glycols using tertiary amine oxides as the oxidant Tetrahedron Lett. 1976, 17 (23) 1973-1976
29. Smith, J. A.; Maloney, D. J.; Clark, D. E.; Xu, Y.; Hecht, S. M.; Lannigan, D. A. Influence of rhamnose substituents on the potency of SL0101, an inhibitor of the Ser/Thr kinase, RSK Bioorg. Med. Chem. 2006, 14 (17) 6034-6042
30. Wang, X.; Li, W.; Williams, M.; Terada, N.; Alessi, D. R.; Proud, C. G. Regulation of elongation factor 2 kinase by p90(RSK1) and p70 S6 kinase EMBO J. 2001, 20 (16) 4370-4379
31. Eisinger-Mathason, T. S.; Andrade, J.; Groehler, A. L.; Clark, D. E.; Muratore-Schroeder, T. L.; Pasic, L.; Smith, J. A.; Shabanowitz, J.; Hunt, D. F.; Macara, I. G.; Lannigan, D. A. Codependent functions of RSK2 and the apoptosis-promoting factor TIA-1 in stress granule assembly and cell survival Mol. Cell 2008, 31 (5) 722-736