Development of Potent, Selective SRPK1 Inhibitors as Potential Topical Therapeutics for Neovascular Eye Disease

ACS Chemical Biology

Volumn 12, Issue 3, 2017, Pages 825-832

  Batson, Jennifer ^a,b   Toop, Hamish D ^a,c   Redondo, Clara ^d   Babaei Jadidi, Roya ^b   Chaikuad, Apirat ^d,f   Wearmouth, Stephen F ^c   Gibbons, Brian ^a   Allen, Claire ^b   Tallant, Cynthia ^d   Zhang, Jingxue ^c   Du, Chunyun ^e   Hancox, Jules C ^e   Hawtrey, Tom ^c   Da Rocha, Joana ^c   Griffith, Renate ^c   Knapp, Stefan ^d,f   Bates, David O ^a,b   Morris, Jonathan C ^c  

^a Milton Science Park   (United Kingdom)

^b UNIVERSITY OF NOTTINGHAM   (United Kingdom)

^c UNIVERSITY OF NEW SOUTH WALES   (Australia)

^d UNIVERSITY OF OXFORD   (United Kingdom)

^e UNIVERSITY OF BRISTOL   (United Kingdom)

^f GOETHE UNIVERSITY   (Germany)

Author keywords

[No Author keywords available]

Indexed keywords

EYE DROPS; PAZOPANIB; PROTEIN KINASE INHIBITOR; SERINE ARGININE RICH PROTEIN; SERINE ARGININE RICH PROTEIN KINASE 1; SERINE ARGININE RICH PROTEIN KINASE 1 INHIBITOR; SERINE ARGININE RICH SPLICING FACTOR; SERINE ARGININE RICH SPLICING FACTOR 1; SPHINX 31; UNCLASSIFIED DRUG; VASCULOTROPIN; VASCULOTROPIN A; ENZYME INHIBITOR; PROTEIN SERINE THREONINE KINASE; SRPK1 PROTEIN, HUMAN;

ALPHA HELIX; ANGIOGENESIS; ANIMAL CELL; ANIMAL EXPERIMENT; ANTIANGIOGENIC ACTIVITY; ARTICLE; CHOROID; CONTROLLED STUDY; CORNEA NEOVASCULARIZATION; CYTOTOXICITY; DRUG BINDING; DRUG DESIGN; DRUG EFFICACY; DRUG POTENCY; DRUG SELECTIVITY; ENZYME ACTIVITY; ENZYME INHIBITION; HINGE REGION; IC50; IN VITRO STUDY; IN VIVO STUDY; MOUSE; NONHUMAN; PRIORITY JOURNAL; PROTEIN PHOSPHORYLATION; PROTEIN SPLICING; RETINA BLOOD VESSEL; RETINAL PIGMENT EPITHELIUM; SUBRETINAL NEOVASCULARIZATION; ANTAGONISTS AND INHIBITORS; CHOROIDAL NEOVASCULARIZATION; HUMAN; INTRAOCULAR DRUG ADMINISTRATION;

ADMINISTRATION, OPHTHALMIC; CHOROIDAL NEOVASCULARIZATION; ENZYME INHIBITORS; HUMANS; PROTEIN-SERINE-THREONINE KINASES;

EID: 85015740751     PISSN: 15548929     EISSN: 15548937     Source Type: Journal    
DOI: 10.1021/acschembio.6b01048     Document Type: Article

References (30)

1. Hoeben, A., Landuyt, B., Highley, M. S., Wildiers, H., Van Oosterom, A. T., and De Bruijn, E. A. (2004) Vascular endothelial growth factor and angiogenesis Pharmacological Rev. 56, 549-580 10.1124/pr.56.4.3
2. Penn, J. S., Madan, A., Caldwell, R. B., Bartoli, M., Caldwell, R. W., and Hartnett, M. E. (2008) Vascular endothelial growth factor in eye disease Prog. Retinal Eye Res. 27, 331-371 10.1016/j.preteyeres.2008.05.001
3. Folkman, J., Merler, E., Abernathy, C., and Williams, G. (1971) Isolation of a tumor factor responsible for angiogenesis J. Exp. Med. 133, 275-288 10.1084/jem.133.2.275
4. Niu, G. and Chen, X. (2010) Vascular endothelial growth factor as an anti-angiogenic target for cancer therapy Curr. Drug Targets 11, 1000-1017 10.2174/138945010791591395
5. Houck, K. A., Leung, D. W., Rowland, A. M., Winer, J., and Ferrara, N. (1992) Dual regulation of vascular endothelial growth factor bioavailability by genetic and proteolytic mechanisms J. Biol. Chem. 267, 26031-26037
6. Amin, E. M., Oltean, S., Hua, J., Gammons, M. V. R., Hamdollah-Zadeh, M., Welsh, G. I., Cheung, M.-L., Ni, L., Kase, S., Rennel, E. S., Symonds, K. E., Nowak, D. G., Royer-Pokora, B., Saleem, M. A., Hagiwara, M., Schumacher, V. A., Harper, S. J., Hinton, D. R., Bates, D. O., and Ladomery, M. R. (2011) WT1 mutants reveal SRPK1 to be a downstream angiogenesis target by altering VEGF splicing Cancer Cell 20, 768-780 10.1016/j.ccr.2011.10.016
7. Harper, S. J. and Bates, D. O. (2008) VEGF-A splicing: the key to anti-angiogenic therapeutics? Nat. Rev. Cancer 8, 1250-1257 10.1038/nrc2505
8. Artac, R. A., McFee, R. M., Longfellow Smith, R. A., Baltes-Breitwisch, M. M., Clopton, D. T., and Cupp, A. S. (2009) Neutralization of vascular endothelial growth factor antiangiogenic isoforms is more effective than treatment with proangiogenic isoforms in stimulating vascular development and follicle progression in the perinatal rat ovary Biol. Reprod. 81, 978-988 10.1095/biolreprod.109.078097
9. Sanford, J. R., Ellis, J. D., Cazalla, D., and Caceres, J. F. (2005) Reversible phosphorylation differentially affects nuclear and cytoplasmic functions of splicing factor 2/alternative splicing factor Proc. Natl. Acad. Sci. U. S. A. 102, 15042-15047 10.1073/pnas.0507827102
10. Karni, R., de Stanchina, E., Lowe, S. W., Sinha, R., Mu, D., and Krainer, A. R. (2007) The gene encoding the splicing factor SF2/ASF is a proto-oncogene Nat. Struct. Mol. Biol. 14, 185-193 10.1038/nsmb1209
11. Nowak, D. G., Amin, E. M., Rennel, E. S., Hoareau-Aveilla, C., Gammons, M., Damodoran, G., Hagiwara, M., Harper, S. J., Woolard, J., Ladomery, M., and Bates, D. O. (2010) Regulation of vascular endothelial growth factor (VEGF) splicing from pro-angiogenic to anti-angiogenic isoforms: a novel therapeutic strategy for angiogenesis J. Biol. Chem. 285, 5532-5540 10.1074/jbc.M109.074930
12. Nowak, D. G., Woolard, J., Amin, E. M., Konopatskaya, O., Saleem, M. A., Churchill, A. J., Ladomery, M. R., Harper, S. J., and Bates, D. O. (2008) Expression of pro- and anti-angiogenic isoforms of VEGF is differentially regulated by splicing and growth factors J. Cell Sci. 121, 3487-3495 10.1242/jcs.016410
13. Oltean, S., Gammons, M., Hulse, R., Hamdollah-Zadeh, M., Mavrou, A., Donaldson, L., Salmon, A. H., Harper, S. J., Ladomery, M. R., and Bates, D. O. (2012) SRPK1 inhibition in vivo: modulation of VEGF splicing and potential treatment for multiple diseases Biochem. Soc. Trans. 40, 831-835 10.1042/BST20120051
14. Ergorul, C., Ray, A., Huang, W., Darland, D., Luo, Z. K., and Grosskreutz, C. L. (2008) Levels of vascular endothelial growth factor-A165b (VEGF-A165b) are elevated in experimental glaucoma Mol. Vis. 14, 1517-1524
15. Merdzhanova, G., Gout, G. S., Keramidas, M., Edmond, V., Coll, J. L., Brambilla, C., Brambilla, E., Gazzeri, S., and Eymin, B. (2010) The transcription factor E2F1 and the SR protein SC35 control the ratio of pro-angiogenic versus antiangiogenic isoforms of vascular endothelial growth factor-A to inhibit neovascularization in vivo Oncogene 29, 5392-5403 10.1038/onc.2010.281
16. Li, Z. Y., Zhu, F., Hu, J. L., Peng, G., Chen, J., Zhang, S., Chen, X., Zhang, R. G., Chen, L. I., Liu, P., Luo, M., Sun, Z. H., Ren, J. H., Huang, L. L., and Wu, G. S. (2011) Sp1 inhibition-mediated upregulation of VEGF165b induced by rh-endostatin enhances antiangiogenic and anticancer effect of rh-endostatin in A549 Tumor Biol. 32, 677-687 10.1007/s13277-011-0168-3
17. Gammons, M. V., Fedorov, O., Ivison, D., Du, C., Clark, T., Hopkins, C., Hagiwara, M., Dick, A. D., Cox, R., Harper, S. J., Hancox, J. C., Knapp, S., and Bates, D. O. (2013) Topical Antiangiogenic SRPK1 Inhibitors Reduce Choroidal Neovascularization in Rodent Models of Exudative AMD Invest. Ophthalmol. Visual Sci. 54, 6052-6062 10.1167/iovs.13-12422
18. Hayes, G. M., Carrigan, P. E., and Miller, L. J. (2007) Serine-arginine protein kinase 1 overexpression is associated with tumorigenic imbalance in mitogen-activated protein kinase pathways in breast, colonic, and pancreatic carcinomas Cancer Res. 67, 2072-2080 10.1158/0008-5472.CAN-06-2969
19. Mavrou, A., Brakspear, K., Hamdollah-Zadeh, M., Damodaran, G., Babaei-Jadidi, R., Oxley, J., Gillatt, D. A., Ladomery, M. R., Harper, S. J., Bates, D. O., and Oltean, S. (2015) Serine-arginine protein kinase 1 (SRPK1) inhibition as a potential novel targeted therapeutic strategy in prostate cancer Oncogene 34, 4311-4319 10.1038/onc.2014.360
20. Gammons, M. V., Lucas, R., Dean, R., Coupland, S. E., Oltean, S., and Bates, D. O. (2014) Targeting SRPK1 to control VEGF-mediated tumour angiogenesis in metastatic melanoma Br. J. Cancer 111, 477-485 10.1038/bjc.2014.342
21. Fukuhara, T., Hosoya, T., Shimizu, S., Sumi, K., Oshiro, T., Yoshinaka, Y., Suzuki, M., Yamamoto, N., Herzenberg, L. A., Herzenberg, L. A., and Hagiwara, M. (2006) Utilization of host SR protein kinases and RNA-splicing machinery during viral replication Proc. Natl. Acad. Sci. U. S. A. 103, 11329-11333 10.1073/pnas.0604616103
22. Székelyhidi, Z., Pató, J., Wáczek, F., Bánhegyi, P., Hegymegi-Barakonyi, B., Ero, D., Mészáros, G., Hollósy, F., Hafenbradl, D., Obert, S., Klebl, B., Kéri, G., and Orfi, L. (2005) Synthesis of selective SRPK-1 inhibitors: novel tricyclic quinoxaline derivatives Bioorg. Med. Chem. Lett. 15, 3241-3246 10.1016/j.bmcl.2005.04.064
23. Morooka, S., Hoshina, M., Kii, I., Okabe, T., Kojima, H., Inoue, N., Okuno, Y., Denawa, M., Yoshida, S., Fukuhara, J., Ninomiya, K., Ikura, T., Furuya, T., Nagano, T., Noda, K., Ishida, S., Hosoya, T., Ito, N., Yoshimura, N., and Hagiwara, M. (2015) Identification of a Dual Inhibitor of SRPK1 and CK2 That Attenuates Pathological Angiogenesis of Macular Degeneration in Mice Mol. Pharmacol. 88, 316-325 10.1124/mol.114.097345
24. Muller, S., Chaikuad, A., Gray, N. S., and Knapp, S. (2015) The ins and outs of selective kinase inhibitor development Nat. Chem. Biol. 11, 818-821 10.1038/nchembio.1938
25. Ghosh, G. and Adams, J. A. (2011) Phosphorylation mechanism and structure of serine-arginine protein kinases FEBS J. 278, 587-597 10.1111/j.1742-4658.2010.07992.x
26. Federov, O., Niesen, F. H., and Knapp, S. in Kinase Inhibitors: Methods and Protocols, Methods Mol. Biol., Vol. 795 (Kuster, B., Ed.), pp 109-118, Springer, 2011.
27. Koeberle, S. C., Fischer, S., Schollmeyer, D., Schattel, V., Grütter, C., Rauh, D., and Laufer, S. A. (2012) Design, Synthesis, and Biological Evaluation of Novel Disubstituted Dibenzosuberones as Highly Potent and Selective Inhibitors of p38 Mitogen Activated Protein Kinase J. Med. Chem. 55, 5868-5877 10.1021/jm300327h
28. Siqueira, R. P., de Almeida Alves Barbosa, é., Polêto, M. D., Righetto, G. L., Seraphim, T. V., Salgado, R. L., Ferreira, J. G., de Andrade Barros, M. V., de Olivera, L. L., Laranjeira, A. B. A., Almeida, M. R., Júnior, A. S., Fietto, J. L. R., Kobarg, J., de Oliveira, E. B., Teixeira, R. R., Borges, J. C., Yunes, J. A., and Bressan, G. C. (2015) Potential Antileukemia Effect and Structural Analyses of SRPK Inhibition by N-(2-(Piperidin-1-yl)-5-(Trifluoromethyl)Phenyl)Isonicotinamide (SRPIN340) PLoS One 10, e0134882 10.1371/journal.pone.0134882
29. Saishin, Y., Saishin, Y., Takahashi, K., Lima e Silva, R., Hylton, D., Rudge, J. S., Wiegand, S. J., and Campochiaro, P. A. (2003) VEGF-TRAP(R1R2) suppresses choroidal neovascularization and VEGF-induced breakdown of the blood-retinal barrier J. Cell. Physiol. 195 (2) 241-8 10.1002/jcp.10246
30. Hua, J., Spee, C., Kase, S., Rennel, E. S., Magnussen, A. L., Qiu, Y., Varey, A., Dhayade, S., Churchill, A. J., Harper, S. J., Bates, D. O., and Hinton, D. R. (2010) Recombinant human VEGF165b inhibits experimental choroidal neovascularization Invest. Ophthalmol. Visual Sci. 51 (8) 4282-8 10.1167/iovs.09-4360