Targeted degradation of proteins localized in subcellular compartments by hybrid small molecules

Molecular Pharmacology

Volumn 91, Issue 3, 2017, Pages 159-166

  Okuhira, Keiichiro ^a,b   Shoda, Takuji ^a   Omura, Risa ^b   Ohoka, Nobumichi ^a   Hattori, Takayuki ^a   Shibata, Norihito ^a   Demizu, Yosuke ^a   Sugihara, Ryo ^b   Ichino, Asato ^b   Kawahara, Haruka ^b   Itoh, Yukihiro ^c   Ishikawa, Minoru ^c   Hashimoto, Yuichi ^c   Kurihara, Masaaki ^a   Itoh, Susumu ^d   Saito, Hiroyuki ^b   Naito, Mikihiko ^a  

^a NATIONAL INSTITUTE OF HEALTH SCIENCES   (Japan)

^b UNIVERSITY OF TOKUSHIMA   (Japan)

^c UNIVERSITY OF TOKYO   (Japan)

^d SHOWA PHARMACEUTICAL UNIVERSITY   (Japan)

Author keywords

[No Author keywords available]

Indexed keywords

BESTATIN; CELLULAR RETINOIC ACID BINDING PROTEIN II; INHIBITOR OF APOPTOSIS PROTEIN 1; INHIBITOR OF APOPTOSIS PROTEIN 2; MEMBRANE PROTEIN; MITOCHONDRIAL PROTEIN; NUCLEAR PROTEIN; PEPTIDE DERIVATIVE; PROTEASOME; RETINOIC ACID BINDING PROTEIN; SMALL INTERFERING RNA; SPECIFIC AND NONGENIC IAP DEPENDENT PROTEIN ERASER(CRABP) 11; SPECIFIC AND NONGENIC IAP DEPENDENT PROTEIN ERASER(CRABP) 4; UBIQUITIN; UBIQUITIN PROTEIN LIGASE E3; UNCLASSIFIED DRUG; X LINKED INHIBITOR OF APOPTOSIS; MOLECULAR LIBRARY; PROTEIN; RETINOIC ACID BINDING PROTEIN II, CELLULAR; RETINOIC ACID RECEPTOR;

ARTICLE; CELL COMPARTMENTALIZATION; CONTROLLED STUDY; CYTOSOL; DRUG TARGETING; GENE SILENCING; HUMAN; HUMAN CELL; HYBRID; INTRACELLULAR SIGNALING; MOLECULARLY TARGETED THERAPY; PRIORITY JOURNAL; PROTEIN DEGRADATION; PROTEIN EXPRESSION; PROTEIN INDUCTION; PROTEIN LOCALIZATION; CELL FRACTIONATION; CELL MEMBRANE; CELL NUCLEUS; CELL ORGANELLE; METABOLISM; MOLECULAR LIBRARY; TUMOR CELL LINE;

CELL LINE, TUMOR; CELL MEMBRANE; CELL NUCLEUS; CYTOSOL; HUMANS; MITOCHONDRIAL PROTEINS; ORGANELLES; PROTEASOME ENDOPEPTIDASE COMPLEX; PROTEINS; PROTEOLYSIS; RECEPTORS, RETINOIC ACID; SMALL MOLECULE LIBRARIES; SUBCELLULAR FRACTIONS; X-LINKED INHIBITOR OF APOPTOSIS PROTEIN;

EID: 85012096156     PISSN: 0026895X     EISSN: 15210111     Source Type: Journal    
DOI: 10.1124/mol.116.105569     Document Type: Article

References (28)

1. Bondeson DP, Mares A, Smith IE, Ko E, Campos S, Miah AH, Mulholland KE, Routly N, Buckley DL, Gustafson JL, et al. (2015) Catalytic in vivo protein knockdown by small-molecule PROTACs. Nat Chem Biol 11:611-617.
2. Chen DY, Lee Y, Van Tine BA, Searleman AC, Westergard TD, Liu H, Tu HC, Takeda S, Dong Y, Piwnica-Worms DR, et al. (2012) A pharmacologic inhibitor of the protease Taspase1 effectively inhibits breast and brain tumor growth. Cancer Res 72:736-746.
3. Delva L, Bastie JN, Rochette-Egly C, Kraïba R, Balitrand N, Despouy G, Chambon P, and Chomienne C (1999) Physical and functional interactions between cellular retinoic acid binding protein II and the retinoic acid-dependent nuclear complex. Mol Cell Biol 19:7158-7167.
4. Demizu Y, Okuhira K, Motoi H, Ohno A, Shoda T, Fukuhara K, Okuda H, Naito M, and Kurihara M (2012) Design and synthesis of estrogen receptor degradation inducer based on a protein knockdown strategy. Bioorg Med Chem Lett 22:1793-1796.
5. Drenberg CD, Baker SD, and Sparreboom A (2013) Integrating clinical pharmacology concepts in individualized therapy with tyrosine kinase inhibitors. Clin Pharmacol Ther 93:215-219.
6. Gilmore KJ, Quinn HE, and Wilson MR (2001) Pinocytic loading of cytochrome c into intact cells specifically induces caspase-dependent permeabilization of mitochondria: evidence for a cytochrome c feedback loop. Cell Death Differ 8:631-639.
7. Holohan C, Van Schaeybroeck S, Longley DB, and Johnston PG (2013) Cancer drug resistance: an evolving paradigm. Nat Rev Cancer 13:714-726.
8. Hung MC and Link W (2011) Protein localization in disease and therapy. J Cell Sci 124:3381-3392.
9. Itoh Y, Ishikawa M, Kitaguchi R, Okuhira K, Naito M, and Hashimoto Y (2012) Double protein knockdown of cIAP1 and CRABP-II using a hybrid molecule consisting of ATRA and IAPs antagonist. Bioorg Med Chem Lett 22:4453-4457.
10. Itoh Y, Ishikawa M, Kitaguchi R, Sato S, Naito M, and Hashimoto Y (2011a) Development of target protein-selective degradation inducer for protein knockdown. Bioorg Med Chem 19:3229-3241.
11. Itoh Y, Ishikawa M, Naito M, and Hashimoto Y (2010) Protein knockdown using methyl bestatin-ligand hybrid molecules: design and synthesis of inducers of ubiquitination-mediated degradation of cellular retinoic acid-binding proteins. J Am Chem Soc 132:5820-5826.
12. Itoh Y, Kitaguchi R, Ishikawa M, Naito M, and Hashimoto Y (2011b) Design, synthesis and biological evaluation of nuclear receptor-degradation inducers. Bioorg Med Chem 19:6768-6778.
13. Jung HS, Rajasekaran N, Ju W, and Shin YK (2015) Human papillomavirus: current and future RNAi therapeutic strategies for cervical cancer. J Clin Med 4:1126-1155.
14. Kirchhoff F (2008) Silencing HIV-1 in vivo. Cell 134:566-568.
15. Muller PA and Vousden KH (2013) p53 Mutations in cancer. Nat Cell Biol 15:2-8.
16. Nantajit D, Fan M, Duru N, Wen Y, Reed JC, and Li JJ (2010) Cyclin B1/Cdk1 phosphorylation of mitochondrial p53 induces anti-apoptotic response. PLoS One 5:e12341.
17. Ohoka N, Nagai K, Hattori T, Okuhira K, Shibata N, Cho N, and Naito M (2014) Cancer cell death induced by novel small molecules degrading the TACC3 protein via the ubiquitin-proteasome pathway. Cell Death Dis 5:e1513.
18. Okuhira K, Demizu Y, Hattori T, Ohoka N, Shibata N, Kurihara M, and Naito M (2016) Molecular design, synthesis, and evaluation of SNIPER(ER) that induces proteasomal degradation of ERα. Methods Mol Biol 1366:549-560.
19. Okuhira K, Demizu Y, Hattori T, Ohoka N, Shibata N, Nishimaki-Mogami T, Okuda H, Kurihara M, and Naito M (2013) Development of hybrid small molecules that induce degradation of estrogen receptor-alpha and necrotic cell death in breast cancer cells. Cancer Sci 104:1492-1498.
20. Okuhira K, Ohoka N, Sai K, Nishimaki-Mogami T, Itoh Y, Ishikawa M, Hashimoto Y, and Naito M (2011) Specific degradation of CRABP-II via cIAP1-mediated ubiquitylation induced by hybrid molecules that crosslink cIAP1 and the target protein. FEBS Lett 585:1147-1152.
21. Ozcan G, Ozpolat B, Coleman RL, Sood AK, and Lopez-Berestein G (2015) Preclinical and clinical development of siRNA-based therapeutics. Adv Drug Deliv Rev 87:108-119.
22. Pylayeva-Gupta Y, Grabocka E, and Bar-Sagi D (2011) RAS oncogenes: weaving a tumorigenic web. Nat Rev Cancer 11:761-774.
23. Resh MD (1999) Fatty acylation of proteins: new insights into membrane targeting of myristoylated and palmitoylated proteins. Biochim Biophys Acta 1451:1-16.
24. Sekine K, Takubo K, Kikuchi R, Nishimoto M, Kitagawa M, Abe F, Nishikawa K, Tsuruo T, and Naito M (2008) Small molecules destabilize cIAP1 by activating auto-ubiquitylation. J Biol Chem 283:8961-8968.
25. Toure M and Crews CM (2016) Small-molecule PROTACS: new approaches to protein degradation. Angew Chem Int Ed Engl 55:1966-1973.
26. Varfolomeev E, Blankenship JW, Wayson SM, Fedorova AV, Kayagaki N, Garg P, Zobel K, Dynek JN, Elliott LO, Wallweber HJ, et al. (2007) IAP antagonists induce autoubiquitination of c-IAPs, NF-κB activation, and TNFα-dependent apoptosis. Cell 131:669-681.
27. Winter GE, Buckley DL, Paulk J, Roberts JM, Souza A, Dhe-Paganon S, and Bradner JE (2015) Drug Development. Phthalimide conjugation as a strategy for in vivo target protein degradation. Science 348:1376-1381.
28. Yoshimaru T, Komatsu M, Matsuo T, Chen YA, Murakami Y, Mizuguchi K, Mizohata E, Inoue T, Akiyama M, Yamaguchi R, et al. (2013) Targeting BIG3-PHB2 interaction to overcome tamoxifen resistance in breast cancer cells. Nat Commun 4:2443.