Targeted drug delivery through the traceless release of tertiary and heteroaryl amines from antibody-drug conjugates

Nature Chemistry

Volumn 8, Issue 12, 2016, Pages 1112-1119

  Staben, Leanna R ^a   Koenig, Stefan G ^a   Lehar, Sophie M ^a   Vandlen, Richard ^a   Zhang, Donglu ^a   Chuh, Josefa ^a   Yu, Shang Fan ^a   Ng, Carl ^a   Guo, Jun ^a   Liu, Yanzhou ^a   Fourie O'Donohue, Aimee ^a   Go, Maryann ^a   Linghu, Xin ^a   Segraves, Nathaniel L ^a   Wang, Tao ^b   Chen, Jinhua ^b   Wei, Binqing ^a   Phillips, Gail D Lewis ^a   Xu, Keyang ^a   Kozak, Katherine R ^a   Mariathasan, Sanjeev ^a   Flygare, John A ^a   Pillow, Thomas H ^a   more..

^a GENENTECH INC   (United States)

^b WUXI APPTEC   (China)

Author keywords

[No Author keywords available]

Indexed keywords

AMINE; ANTIBODY CONJUGATE; ANTIINFECTIVE AGENT; ANTINEOPLASTIC AGENT; CATHEPSIN; DRUG; DRUG CARRIER; MONOCLONAL ANTIBODY; QUATERNARY AMMONIUM DERIVATIVE;

CELL SURVIVAL; CHEMICAL PHENOMENA; CHEMISTRY; DRUG EFFECT; DRUG RELEASE; DRUG STABILITY; HUMAN; METABOLISM; SOLUBILITY; TUMOR CELL LINE;

AMINES; ANTI-BACTERIAL AGENTS; ANTIBODIES, MONOCLONAL; ANTINEOPLASTIC AGENTS; CATHEPSINS; CELL LINE, TUMOR; CELL SURVIVAL; DRUG CARRIERS; DRUG LIBERATION; DRUG STABILITY; HUMANS; HYDROPHOBIC AND HYDROPHILIC INTERACTIONS; IMMUNOCONJUGATES; PHARMACEUTICAL PREPARATIONS; QUATERNARY AMMONIUM COMPOUNDS; SOLUBILITY;

EID: 84996483782     PISSN: 17554330     EISSN: 17554349     Source Type: Journal    
DOI: 10.1038/nchem.2635     Document Type: Article

References (44)

1. Pérez-Herrero, E., Fernández-Medarde, A. Advanced targeted therapies in cancer: drug nanocarriers, the future of chemotherapy. Eur. J. Pharm. Biopharm. 93, 52-79 (2015).
2. Chari, R. V. J., Miller, M. L., Widdison, W. C. Antibody-drug conjugates: an emerging concept in cancer therapy. Angew. Chem. Int. Ed. 53, 3796-3827 (2014).
3. Kratz, F., Müller, I. A., Ryppa, C., Warnecke, A. Prodrug strategies in anticancer chemotherapy. ChemMedChem 3, 20-53 (2008).
4. Guillemard, V., Uri Saragovi, H. Prodrug chemotherapeutics bypass P-glycoprotein resistance and kill tumors in vivo with high efficacy and target-dependent selectivity. Oncogene 23, 3613-3621 (2004).
5. Dubikovskaya, E. A., Thorne, S. H., Pillow, T. H., Contag, C. H., Wender, P. A. Overcoming multidrug resistance of small-molecule therapeutics through conjugation with releasable octaarginine transporters. Proc. Natl Acad. Sci. USA 105, 12128-12133 (2008).
6. Kirtane, A. R., Kalscheuer, S. M., Panyam, J. Exploiting nanotechnology to overcome tumor drug resistance: challenges and opportunities. Adv. Drug Deliv. Rev. 65, 1731-1747 (2013).
7. Kratz, F., Abu Ajaj, K., Warnecke, A. Anticancer carrier-linked prodrugs in clinical trials. Expert Opin. Invest. Drugs 16, 1037-1058 (2007).
8. Van Bambeke, F., Barcia-Macay, M., Lemaire, S., Tulkens, P. M. Cellular pharmacodynamics and pharmacokinetics of antibiotics: current views and perspectives. Curr. Opin. Drug Discov. Dev. 9, 218-230 (2006).
9. Lehar, S. M. et al. Novel antibody-antibiotic conjugate eliminates intracellular S. aureus. Nature 527, 323-328 (2015).
10. Wang, R. E. et al. An immunosuppressive antibody-drug conjugate. J. Am. Chem. Soc. 137, 3229-3232 (2015).
11. Dubowchik, G. M., Firestone, R. A. Cathepsin B-sensitive dipeptide prodrugs. 1. A model study of structural requirements for efficient release of doxorubicin. Bioorg. Med. Chem. Lett. 8, 3341-3346 (1998).
12. Carl, P. L., Chakravarty, P. K., Katzenellenbogen, J. A. A novel connector linkage applicable in prodrug design. J. Med. Chem. 24, 479-480 (1981).
13. Doronina, S. O. et al. Development of potent monoclonal antibody auristatin conjugates for cancer therapy. Nat. Biotechnol. 21, 778-784 (2003).
14. Gromek, S. M., Balunas, M. J. Natural products as exquisitely potent cytotoxic payloads for antibody-drug conjugates. Curr. Top. Med. Chem. 14, 2822-2834 (2015).
15. Adem, Y. T. et al. Auristatin antibody-drug conjugate physical instability and the role of drug payload. Bioconjugate Chem. 25, 656-664 (2014).
16. Chennamsetty, N., Voynov, V., Kayser, V., Helk, B., Trout, B. L. Design of therapeutic proteins with enhanced stability. Proc. Natl Acad. Sci. USA 106, 11937-11942 (2009).
17. Zhao, R. Y. et al. Synthesis and evaluation of hydrophilic linkers for antibody-maytansinoid conjugates. J. Med. Chem. 54, 3606-3623 (2011).
18. Jeffrey, S. C. et al. Design, synthesis, and in vitro evaluation of dipeptide-based antibody minor groove binder conjugates. J. Med. Chem. 48, 1344-1358 (2005).
19. Xiao, J., Burn, A., Tolbert, T. J. Increasing solubility of proteins and peptides by site-specific modification with betaine. Bioconjugate Chem. 19, 1113-1118 (2008).
20. Stephanopoulos, N., Francis, M. B. Choosing an effective protein bioconjugation strategy. Nat. Chem. Biol. 7, 876-884 (2011).
21. Agarwal, P., Bertozzi, C. R. Site-specific antibody-drug conjugates: the nexus of bioorthogonal chemistry, protein engineering, and drug development. Bioconjugate Chem. 26, 176-192 (2015).
22. Spicer, C. D., Davis, B. G. Selective chemical protein modification. Nat. Commun. 5, 4740 (2014).
23. Russell, G. A., Danen, W. C. Electron-transfer processes. VIII. Coupling reactions of radicals with carbanions. J. Am. Chem. Soc. 90, 347-353 (1968).
24. Stock, L. M., Wasielewski, M. R. Electron paramagnetic resonance spectra of ?-substituted nitrotoluene anion radicals. Influence of electron-withdrawing substituents on the coupling constants for ?-hydrogen atoms. J. Am. Chem. Soc. 97, 5620-5622 (1975).
25. Tercel, M., Wilson, W. R., Denny, W. A. Nitrobenzyl mustard quaternary salts: a new class of hypoxia-selective cytotoxins showing very high in vitro selectivity. J. Med. Chem. 36, 2578-2579 (1993).
26. Hansch, C., Leo, A., Taft, R. W. A survey of Hammett substituent constants and resonance and field parameters. Chem. Rev. 91, 165-195 (1991).
27. Mohamed, M. M., Sloane, B. F. Cysteine cathepsins: multifunctional enzymes in cancer. Nat. Rev. Cancer 6, 764-775 (2006).
28. Musil, D. et al. The refined 2. 15 Å X-ray crystal structure of human liver cathepsin B: the structural basis for its specificity. EMBO J. 10, 2321-2330 (1991).
29. Pettit, G. R. et al. The isolation and structure of a remarkable marine animal antineoplastic constituent: dolastatin 10. J. Am. Chem. Soc. 109, 6883-6885 (1987).
30. Maderna, A. et al. Discovery of cytotoxic dolastatin 10 analogues with N-terminal modifications. J. Med. Chem. 57, 10527-10543 (2014).
31. Steinmetz, H. et al. Isolation, crystal and solution structure determination, and biosynthesis of tubulysins-powerful inhibitors of tubulin polymerization from myxobacteria. Angew. Chem. Int. Ed. 43, 4888-4892 (2004).
32. Barker, T. J., Duncan, K. K., Otrubova, K., Boger, D. L. Potent vinblastine C20? ureas displaying additionally improved activity against a vinblastine-resistant cancer cell line. ACS Med. Chem. Lett. 4, 985-988 (2013).
33. Laguzza, B. C. et al. New antitumor monoclonal antibody-vinca conjugates LY203725 and related compounds: design, preparation, and representative in vivo activity. J. Med. Chem. 32, 548-555 (1989).
34. Henry, G. D. De novo synthesis of substituted pyridines. Tetrahedron 60, 6043-6061 (2004).
35. Wienecke, A., Bacher, G. Indibulin, a novel microtubule inhibitor, discriminates betweenmature neuronal and nonneuronal tubulin. Cancer Res. 69, 171-177 (2009).
36. Pauli, J. et al. Suitable labels for molecular imaging-influence of dye structure and hydrophilicity on the spectroscopic properties of IgG conjugates. Bioconjugate Chem. 22, 1298-1308 (2011).
37. Flygare, J. A. et al. Peptidomimetic compounds and antibody-drug conjugates thereof. World Intellectual Property Organization patent 2015/095227 A2 (2015).
38. Jones, L. R., et al. Releasable luciferin-transporter conjugates: tools for the real-time analysis of cellular uptake and release. J. Am. Chem. Soc. 128, 6526-6527 (2006).
39. Yang, J., Chen, H., Vlahov, I. R., Cheng, J.-X., Low, P. S. Evaluation of disulfide reduction during receptor-mediated endocytosis by using FRET imaging. Proc. Natl Acad. Sci. USA 103, 13872-13877 (2006).
40. Vlahov, I. R. et al. An assembly concept for the consecutive introduction of unsymmetrical disulfide bonds: synthesis of a releasable multidrug conjugate of folic acid. J. Org. Chem. 72, 5968-5972 (2007).
41. Pillow, T. et al. Decoupling stability and release in disulfide bonds with antibodysmallmolecule conjugates. Chem. Sci. http://dx. doi. org/10. 1039/C6SC01831A (2016).
42. Miles, L. W. C., Owen, L. N. 149. Dithiols. part XII. The alkaline hydrolysis of acetylated hydroxy-thiols: a new reaction for the formation of cyclic sulphides. J. Chem. Soc. http://dx. doi. org/10. 1039/JR9520000817 (1952).
43. Satyam, A. Design and synthesis of releasable folate-drug conjugates using a novel heterobifunctional disulfide-containing linker. Bioorg. Med. Chem. Lett. 18, 3196-3199 (2008).
44. Junutula, J. R. et al. Site-specific conjugation of a cytotoxic drug to an antibody improves the therapeutic index. Nat. Biotechnol. 26, 925-932 (2008).