Identification of potent agonists of photoreceptor-specific nuclear receptor (NR2E3) and preparation of a radioligand

Bioorganic and Medicinal Chemistry Letters

Volumn 16, Issue 19, 2006, Pages 5001-5004

  Wolkenberg, Scott E ^a   Zhao, Zhijian ^a   Kapitskaya, Marianna ^a   Webber, Andrea L ^a   Petrukhin, Konstantin ^a   Tang, Yui Sing ^a   Dean, Dennis C ^a   Hartman, George D ^a   Lindsley, Craig W ^a  

^a MERCK RESEARCH LABORATORIES   (United States)

Author keywords

Age related macular degeneration; AMD; NR2E3; Nuclear receptor; Ophthalmics; PNR; RNR

Indexed keywords

BENZIMIDAZOLE DERIVATIVE; CELL NUCLEUS RECEPTOR; NUCLEAR RECEPTOR 2E3 AGONIST; TRITIUM; UNCLASSIFIED DRUG;

ARTICLE; BINDING ASSAY; PHOTORECEPTOR;

BENZIMIDAZOLES; BETA-LACTAMASES; CELL LINE; CELL SURVIVAL; HUMANS; LIGANDS; MACULAR DEGENERATION; NUCLEAR PROTEINS; PHOTORECEPTORS; RECEPTORS, CYTOPLASMIC AND NUCLEAR; REPRESSOR PROTEINS; STRUCTURE-ACTIVITY RELATIONSHIP; TRANS-ACTIVATION (GENETICS); TRANSCRIPTION FACTORS;

EID: 33747347011     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bmcl.2006.07.056     Document Type: Article

References (18)

1. Zarbin M.A. Arch. Ophthalmol. 122 (2004) 598
2. Bok D. J. Cell Sci. Suppl. 17 (1993) 189
3. Blomhoff R., Green M.H., and Norum K.R. Annu. Rev. Nutr. 12 (1992) 37
4. Kobayashi M., Takezawa S., Hara K., Yu R.T., Umesono Y., Agata K., Taniwaki M., Yasuda K., and Umesono K. Proc. Natl. Acad. Sci. U.S.A. 96 (1999) 4814
5. Chen F., Figueroa D.J., Marmorstein A.D., Zhang Q., Petrukhin K., Caskey C.T., and Austin C.P. Proc. Natl. Acad. Sci. U.S.A. 96 (1999) 15149
6. Akhmedov N.B., Piriev N.I., Chang B., Rapoport A.L., Hawes N.L., Nishina P.M., Nusinowitz S., Heckenlively J.R., Roderick T.H., Kozak C.A., Danciger M., Davisson M.T., and Farber D.B. Proc. Natl. Acad. Sci. U.S.A. 97 (2000) 5551
7. Haider N.B., Naggert J.K., and Nishina P.M. Hum. Mol. Genet. 10 (2001) 1619
8. Bumsted O'Brien K.M., Cheng H., Jiang Y., Schulte D., Swaroop A., and Hendrickson A.E. Invest. Ophthalmol. Vis. Sci. 45 (2004) 2807
9. Chen J., Rattner A., and Nathans J. J Neurosci. 25 (2005) 118
10. Haider N.B., Jacobson S.G., Cideciyan A.V., Swiderski R., Streb L.M., Searby C., Beck G., Hockey R., Hanna D.B., Gorman S., Duhl D., Carmi R., Bennett J., Weleber R.G., Fishman G.A., Wright A.F., Stone E.M., and Sheffield V.C. Nat. Genet. 24 (2000) 127
11. Milam A.H., Rose L., Cideciyan A.V., Barakat M.R., Tang S.-X., Gupta N., Aleman T.S., Wright A.F., Stone E.M., Sheffield V.C., and Jacobson S.G. Proc. Natl. Acad. Sci. U.S.A. 99 (2002) 473
12. Sharon D., Sandberg M.A., Caruso R.C., Berson E.L., and Dryja T.P. Arch. Ophthalmol. 121 (2003) 1316
13. Michaelides M., Holder G.E., Webster A.R., Hunt D.M., Bird A.C., Fitzke F.W., Mollon J.D., and Moore A.T. Br. J. Ophthalmol. 89 (2006) 332
14. Kapitskaya M., Cunningham M.E., Lacson R., Kornienko O., Bednar B., and Petrukhin K. Assay and Drug Dev. Technol. 4 (2006) 253
15. Luciferase reporter gene assays were performed with extracts from CHO cells which were transiently co-transfected with pG5Luc luciferase reporter plasmid containing GAL4 response elements in its promoter region in combination with pVP16_NR2E3LBD plasmid expressing VP16 activator linked to NR2E3LBD, and pGALDBD_NCOR plasmid expressing GAL4 fusion of co-repressor NCOR. In the absence of ligand, VP16-NR2E3LBD interacts with GALDBD_NCOR which results in constitutative activation of luciferase reporter. Addition of NR2E3 agonists leads to co-repressor release and reduction in luciferase activity.
16. Porter H.K. Org. React. 20 (1973) 455
17. Bamfield, P.; Harvey, E. D.; Hughes, N.; Stead, C. V. G.B. Patent 2,125,791.
18. De Los Angeles J.E., Nikulin V.I., Shams G., Konkar A.A., Mehta R., Feller D.R., and Miller D.D. J. Med. Chem. 39 (1996) 3701