Discovery of diverse small molecule chemotypes with cell-based PKD1 inhibitory activity

PLoS ONE

Volumn 6, Issue 10, 2011, Pages

  Sharlow, Elizabeth R ^a   Wilson, Gabriela Mustata ^c,d   Close, David ^c,d   Leimgruber, Stephanie ^c,d   Tandon, Manuj ^c   Reed, Robyn B ^c,d   Shun, Tong Ying ^c,d   Wang, Q Jane ^c,d   Wipf, Peter ^d   Lazo, John S ^a,b  

^a UNIVERSITY OF VIRGINIA   (United States)

^b UNIVERSITY OF VIRGINIA   (United States)

^c UNIVERSITY OF PITTSBURGH SCHOOL OF MEDICINE   (United States)

^d UNIVERSITY OF PITTSBURGH   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

1 (3 ETHYL 5 METHOXY 1,3 BENZOTHIAZOL 2 YLIDENE)PROPAN 2 ONE; 5 (3 CHLOROPHENYL) N [4 (MORPHOLIN 4 YLMETHYL)PHENYL]FURAN 2 CARBOXAMIDE; 6 [4 (3 AMINOPROPYLAMINO) 6 METHYL 1H PYRIMIDIN 2 YLIDENE]CYCLOHEXA 2,4 DIEN 1 ONE; ADENOSINE TRIPHOSPHATE; AMILORIDE; ANTINEOPLASTIC AGENT; CID 16230; CID 1893668; CID 2011756; CID 2876479; CID 2958734; CID 4438738; CID 5086667; CID 5389142; CID 646236; CID 663844; CID 755673; CID2876479; PHORBOL ESTER; PROTEIN KINASE D; PROTEIN KINASE D1; PROTEIN KINASE D1 INHIBITOR; PROTEIN KINASE INHIBITOR; SANGIVAMYCIN; UNCLASSIFIED DRUG; PROTEIN KINASE C;

ARTICLE; BIOINFORMATICS; CANCER CELL; CELL STRAIN LNCAP; COMPETITIVE INHIBITION; COMPUTER ANALYSIS; CONCENTRATION RESPONSE; CONTROLLED STUDY; DRUG MECHANISM; DRUG SCREENING; DRUG STRUCTURE; ENZYME ASSAY; ENZYME INHIBITION; HIGH THROUGHPUT SCREENING; IC 50; IN VITRO STUDY; MOLECULAR DOCKING; PROSTATE CANCER; STRUCTURE ACTIVITY RELATION; BINDING COMPETITION; CHEMICAL STRUCTURE; CHEMISTRY; DOSE RESPONSE; DRUG ANTAGONISM; DRUG DEVELOPMENT; DRUG EFFECT; ENZYME ACTIVATION; ENZYME ACTIVE SITE; HUMAN; METABOLISM; METHODOLOGY; MOLECULAR GENETICS; MOLECULAR LIBRARY; NUCLEOTIDE SEQUENCE; PHOSPHORYLATION; REPRODUCIBILITY; TUMOR CELL LINE;

ADENOSINE TRIPHOSPHATE; BINDING, COMPETITIVE; CATALYTIC DOMAIN; CELL LINE, TUMOR; CONSERVED SEQUENCE; DOSE-RESPONSE RELATIONSHIP, DRUG; DRUG DISCOVERY; ENZYME ACTIVATION; HIGH-THROUGHPUT SCREENING ASSAYS; HUMANS; MODELS, MOLECULAR; MOLECULAR SEQUENCE DATA; PHORBOL ESTERS; PHOSPHORYLATION; PROTEIN KINASE C; PROTEIN KINASE INHIBITORS; REPRODUCIBILITY OF RESULTS; SMALL MOLECULE LIBRARIES;

EID: 80053610815     PISSN: None     EISSN: 19326203     Source Type: Journal    
DOI: 10.1371/journal.pone.0025134     Document Type: Article

References (37)

1. Wang QJ, (2006) PKD at the crossroads of DAG and PKC signaling. Trends Pharmacol Sci pp. 317-323.
2. Auer A, von Blume J, Sturany S, von Wichert G, Van Lint J, et al. (2005) Role of the regulatory domain of protein kinase D2 in phorbol ester binding, catalytic activity, and nucleocytoplasmic shuttling. Mol Biol Cell 16: 4375-4385.
3. Hao Q, Wang L, Tang H, (2009) Vascular endothelial growth factor induces protein kinase D-dependent production of proinflammatory cytokines in endothelial cells. Am J Physiol Cell Physiol 296: C821-827.
4. Hao Q, Wang L, Zhao ZJ, Tang H, (2009) Identification of protein kinase D2 as a pivotal regulator of endothelial cell proliferation, migration, and angiogenesis. J Biol Chem 284: 799-806.
5. Rey O, Yuan J, Young SH, Rozengurt E, (2003) Protein kinase C nu/protein kinase D3 nuclear localization, catalytic activation, and intracellular redistribution in response to G protein-coupled receptor agonists. J Biol Chem 278: 23773-23785.
6. Rozengurt E, Rey O, Waldron RT, (2005) Protein kinase D signaling. J Biol Chem 280: 13205-13208.
7. Avkiran M, Rowland AJ, Cuello F, Haworth RS, (2008) Protein kinase d in the cardiovascular system: emerging roles in health and disease. Circ Res 102: 157-163.
8. Besirli CG, Johnson EM Jr, (2006) The activation loop phosphorylation of protein kinase D is an early marker of neuronal DNA damage. J Neurochem 99: 218-225.
9. Ha CH, Wang W, Jhun BS, Wong C, Hausser A, et al. (2008) Protein kinase D-dependent phosphorylation and nuclear export of histone deacetylase 5 mediates vascular endothelial growth factor-induced gene expression and angiogenesis. J Biol Chem 283: 14590-14599.
10. Matthews SA, Navarro MN, Sinclair LV, Emslie E, Feijoo-Carnero C, et al. (2010) Unique functions for protein kinase D1 and protein kinase D2 in mammalian cells. Biochem J 432: 153-163.
11. Oster H, Abraham D, Leitges M, (2006) Expression of the protein kinase D (PKD) family during mouse embryogenesis. Gene Expr Patterns 6: 400-408.
12. Rozengurt E, (2011) Protein kinase d signaling: multiple biological functions in health and disease. Physiology (Bethesda) 26: 23-33.
13. Azoitei N, Pusapati GV, Kleger A, Moller P, Kufer R, et al. (2010) Protein kinase D2 is a crucial regulator of tumour cell-endothelial cell communication in gastrointestinal tumours. Gut 59: 1316-1330.
14. Chen J, Deng F, Singh SV, Wang QJ, (2008) Protein kinase D3 (PKD3) contributes to prostate cancer cell growth and survival through a PKCepsilon/PKD3 pathway downstream of Akt and ERK 1/2. Cancer Res 68: 3844-3853.
15. Kim M, Jang HR, Kim JH, Noh SM, Song KS, et al. (2008) Epigenetic inactivation of protein kinase D1 in gastric cancer and its role in gastric cancer cell migration and invasion. Carcinogenesis 29: 629-637.
16. Manning G, Whyte DB, Martinez R, Hunter T, Sudarsanam S, (2002) The protein kinase complement of the human genome. Science 298: 1912-1934.
17. Thompson EE, Kornev AP, Kannan N, Kim C, Ten Eyck LF, et al. (2009) Comparative surface geometry of the protein kinase family. Protein Sci 18: 2016-2026.
18. Sharlow ER, Giridhar KV, LaValle CR, Chen J, Leimgruber S, et al. (2008) Potent and selective disruption of protein kinase D functionality by a benzoxoloazepinolone. J Biol Chem 283: 33516-33526.
19. Sharlow ER, Leimgruber S, Yellow-Duke A, Barrett R, Wang QJ, et al. (2008) Development, validation and implementation of immobilized metal affinity for phosphochemicals (IMAP)-based high-throughput screening assays for low-molecular-weight compound libraries. Nat Protoc 3: 1350-1363.
20. Lavalle CR, Bravo-Altamirano K, Giridhar KV, Chen J, Sharlow E, et al. (2010) Novel protein kinase D inhibitors cause potent arrest in prostate cancer cell growth and motility. BMC Chem Biol 10: 5.
21. Bravo-Altamirano K, George KM, Frantz MC, LaValle CR, Tandon M, et al. (2011) Synthesis and Structure-Activity Relationships of Benzothienothiazepinone Inhibitors of Protein Kinase D. Acs Medicinal Chemistry Letters 2: 154-159.
22. Evans IM, Bagherzadeh A, Charles M, Raynham T, Ireson C, et al. (2010) Characterization of the biological effects of a novel protein kinase D inhibitor in endothelial cells. Biochem J 429: 565-572.
23. Meredith EL, Ardayfio O, Beattie K, Dobler MR, Enyedy I, et al. (2010) Identification of orally available naphthyridine protein kinase D inhibitors. J Med Chem 53: 5400-5421.
24. Meredith EL, Beattie K, Burgis R, Capparelli M, Chapo J, et al. (2010) Identification of potent and selective amidobipyridyl inhibitors of protein kinase D. J Med Chem 53: 5422-5438.
25. Monovich L, Vega RB, Meredith E, Miranda K, Rao C, et al. (2010) A novel kinase inhibitor establishes a predominant role for protein kinase D as a cardiac class IIa histone deacetylase kinase. FEBS Lett 584: 631-637.
26. Gamber GG, Meredith E, Zhu Q, Yan W, Rao C, et al. (2011) 3,5-Diarylazoles as novel and selective inhibitors of protein kinase D. Bioorg Med Chem Lett 21: 1447-1451.
27. Thrower EC, Yuan J, Usmani A, Liu Y, Jones C, et al. (2011) A novel protein kinase D inhibitor attenuates early events of experimental pancreatitis in isolated rat acini. Am J Physiol Gastrointest Liver Physiol 300: G120-129.
28. Harikumar KB, Kunnumakkara AB, Ochi N, Tong Z, Deorukhkar A, et al. (2010) A novel small-molecule inhibitor of protein kinase D blocks pancreatic cancer growth in vitro and in vivo. Mol Cancer Ther 9: 1136-1146.
29. Thomsen R, Christensen MH, (2006) MolDock: a new technique for high-accuracy molecular docking. J Med Chem 49: 3315-3321.
30. Johannes FJ, Prestle J, Dieterich S, Oberhagemann P, Link G, et al. (1995) Characterization of activators and inhibitors of protein kinase C mu. Eur J Biochem 227: 303-307.
31. Muraki M, Ohkawara B, Hosoya T, Onogi H, Koizumi J, et al. (2004) Manipulation of alternative splicing by a newly developed inhibitor of Clks. J Biol Chem 279: 24246-24254.
32. Sharlow ER, Leimgruber S, Shun TY, Lazo JS, (2007) Development and implementation of a miniaturized high-throughput time-resolved fluorescence energy transfer assay to identify small molecule inhibitors of polo-like kinase 1. Assay Drug Dev Technol 5: 723-735.
33. Soares KM, Blackmon N, Shun TY, Shinde SN, Takyi HK, et al. (2010) Profiling the NIH Small Molecule Repository for compounds that generate H2O2 by redox cycling in reducing environments. Assay Drug Dev Technol 8: 152-174.
34. Gschwendt M, Dieterich S, Rennecke J, Kittstein W, Mueller HJ, et al. (1996) Inhibition of protein kinase C mu by various inhibitors. Differentiation from protein kinase c isoenzymes. FEBS Lett 392: 77-80.
35. Lochner A, Moolman JA, (2006) The many faces of H89: a review. Cardiovasc Drug Rev 24: 261-274.
36. Goekjian PG, Jirousek MR, (1999) Protein kinase C in the treatment of disease: signal transduction pathways, inhibitors, and agents in development. Curr Med Chem 6: 877-903.
37. Hidaka H, Inagaki M, Kawamoto S, Sasaki Y, (1984) Isoquinolinesulfonamides, novel and potent inhibitors of cyclic nucleotide dependent protein kinase and protein kinase C. Biochemistry 23: 5036-5041.