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Current Topics in Medicinal Chemistry


ISSN (Print): 1568-0266
ISSN (Online): 1873-4294

Review Article

Topoisomerase Inhibitors and Targeted Delivery in Cancer Therapy

Author(s): Fei You* and Changshou Gao

Volume 19 , Issue 9 , 2019

Page: [713 - 729] Pages: 17

DOI: 10.2174/1568026619666190401112948

Price: $65


DNA topoisomerases are enzymes that catalyze the alteration of DNA topology with transiently induced DNA strand breakage, essential for DNA replication. Topoisomerases are validated cancer chemotherapy targets. Anticancer agents targeting Topoisomerase I and II have been in clinical use and proven to be highly effective, though with significant side effects. There are tremendous efforts to develop new generation of topoisomerase inhibitors. Targeted delivery of topoisomerase inhibitors is another way to reduce the side effects. Conjugates of topoisomerases inhibitors with antibody, polymer, or small molecule are developed to target these inhibitors to tumor sites.

Keywords: Topoisomerase, Topoisomerase inhibitors, Topology of DNA, DNA strain break, Cancer target, Targeted delivery.

Graphical Abstract
Wang, J.C. DNA topoisomerases. Annu. Rev. Biochem., 1996, 65, 635-692. []. [PMID: 8811192].
Wang, J.C. Cellular roles of DNA topoisomerases: a molecular perspective. Nat. Rev. Mol. Cell Biol., 2002, 3(6), 430-440. []. [PMID: 12042765].
Pommier, Y. DNA topoisomerase I inhibitors: chemistry, biology, and interfacial inhibition. Chem. Rev., 2009, 109(7), 2894-2902. []. [PMID: 19476377].
Pommier, Y. Drugging topoisomerases: lessons and challenges. ACS Chem. Biol., 2013, 8(1), 82-95. []. [PMID: 23259582].
Viard, T.; de la Tour, C.B. Type IA topoisomerases: A simple puzzle? Biochimie, 2007, 89(4), 456-467. []. [PMID: 17141394].
Koster, D.A.; Croquette, V.; Dekker, C.; Shuman, S.; Dekker, N.H. Friction and torque govern the relaxation of DNA supercoils by eukaryotic topoisomerase IB. Nature, 2005, 434(7033), 671-674. []. [PMID: 15800630].
a)D’Arpa, P.; Machlin, P.S.; Ratrie, H., III; Rothfield, N.F.; Cleveland, D.W.; Earnshaw, W.C. cDNA cloning of human DNA topoisomerase I: catalytic activity of a 67.7-kDa carboxyl-terminal fragment. Proc. Natl. Acad. Sci. USA, 1988, 85(8), 2543-2547. []. [PMID: 2833744]
b)Stewart, L.; Ireton, G.C.; Champoux, J.J. Reconstitution of human topoisomerase I by fragment complementation. J. Mol. Biol., 1997, 269(3), 355-372. []. [PMID: 9199405].
Redinbo, M.R.; Stewart, L.; Champoux, J.J.; Hol, W.G. Structural flexibility in human topoisomerase I revealed in multiple non-isomorphous crystal structures. J. Mol. Biol., 1999, 292(3), 685-696. []. [PMID: 10497031].
Redinbo, M.R.; Stewart, L.; Kuhn, P.; Champoux, J.J.; Hol, W.G. Crystal structures of human topoisomerase I in covalent and noncovalent complexes with DNA. Science, 1998, 279(5356), 1504-1513. []. [PMID: 9488644].
a)Hsiang, Y.H.; Hertzberg, R.; Hecht, S.; Liu, L.F. Camptothecin induces protein-linked DNA breaks via mammalian DNA topoisomerase I. J. Biol. Chem., 1985, 260(27), 14873-14878. [PMID: 2997227]
b)Hsiang, Y-H.; Liu, L.F. Identification of mammalian DNA topoisomerase I as an intracellular target of the anticancer drug camptothecin. Cancer Res., 1988, 48(7), 1722-1726. [PMID: 2832051].
Wall, M.E.; Wani, M.C.; Cook, C.E.; Palmer, K.H.; McPhail, A.I.; Sim, G.A. Plant antitumor agents. I. The isolation and structure of camptothecin, a novel alkaloidal leukemia and tumor inhibitor from camptotheca acuminate. J. Am. Chem. Soc., 1966, 88, 3888-3890. [].
Koster, D.A.; Palle, K.; Bot, E.S.; Bjornsti, M.A.; Dekker, N.H. Antitumour drugs impede DNA uncoiling by topoisomerase I. Nature, 2007, 448(7150), 213-217. []. [PMID: 17589503].
Seol, Y.; Zhang, H.; Pommier, Y.; Neuman, K.C. A kinetic clutch governs religation by type IB topoisomerases and determines camptothecin sensitivity. Proc. Natl. Acad. Sci. USA, 2012, 109(40), 16125-16130. []. [PMID: 22991469].
a)Staker, B.L.; Hjerrild, K.; Feese, M.D.; Behnke, C.A.; Burgin, A.B., Jr; Stewart, L. The mechanism of topoisomerase I poisoning by a camptothecin analog. Proc. Natl. Acad. Sci. USA, 2002, 99(24), 15387-15392. []. [PMID: 12426403]
b)Staker, B.L.; Feese, M.D.; Cushman, M.; Pommier, Y.; Zembower, D.; Stewart, L.; Burgin, A.B. Structures of three classes of anticancer agents bound to the human topoisomerase I-DNA covalent complex. J. Med. Chem., 2005, 48(7), 2336-2345. []. [PMID: 15801827].
a)Wall, M.E.; Wani, M.C. Antineoplastic agents from plants. Annu. Rev. Pharmacol. Toxicol., 1977, 17, 117-132. [].[PMID: 326159]
b)Fassberg, J.; Stella, V.J. A kinetic and mechanistic study of the hydrolysis of camptothecin and some analogues. J. Pharm. Sci., 1992, 81(7), 676-684. []. [PMID: 1403703]
c)Ziomkowska, B.; Kruszewski, S.; Siuda, R.; Cyrankiewicz, M. Deactivation rate of camptothecin determined by factor analysis of steady-state fluorescence and adsorption spectra. Opt. Appl., 2006, 36, 137-146.
a)Burke, T.G.; Mi, Z. Preferential binding of the carboxylate form of camptothecin by human serum albumin. Anal. Biochem., 1993, 212(1), 285-287. [].[PMID: 8368506]
b)Burke, T.G.; Mi, Z. The structural basis of camptothecin interactions with human serum albumin: impact on drug stability. J. Med. Chem., 1994, 37(1), 40-46. []. [PMID: 8289200].
Nabiev, I.; Fleury, F.; Kudelina, I.; Pommier, Y.; Charton, F.; Riou, J-F.; Alix, A.J.P.; Manfait, M. Spectroscopic and biochemical characterisation of self-aggregates formed by antitumor drugs of the camptothecin family: their possible role in the unique mode of drug action. Biochem. Pharmacol., 1998, 55(8), 1163-1174. []. [PMID: 9719470].
a)Gottlieb, J.A.; Guarino, A.M.; Call, J.B.; Oliverio, V.T.; Block, J.B. Preliminary pharmacologic and clinical evaluation of camptothecin sodium (NSC-100880). Cancer Chemother. Rep., 1970, 54(6), 461-470. [PMID: 4946015]
b)Muggia, F.M.; Creaven, P.J.; Hansen, H.H.; Cohen, M.H.; Selawry, O.S. Phase I clinical trial of weekly and daily treatment with camptothecin (NSC-100880): correlation with preclinical studies. Cancer Chemother. Rep., 1972, 56(4), 515-521. [PMID: 5081595]
c) Moertel, C.G.; Schutt, A.J.; Reitemeier, R.J.; Hahn, R.G. Phase II study of camptothecin (NSC-100880) in the treatment of advanced gastrointestinal cancer. Cancer Chemother. Rep., 1972, 56(1), 95-101. [PMID: 5030811]
Ioanoviciu, A.; Antony, S.; Pommier, Y.; Staker, B.L.; Stewart, L.; Cushman, M. Synthesis and mechanism of action studies of a series of norindenoisoquinoline topoisomerase I poisons reveal an inhibitor with a flipped orientation in the ternary DNA-enzyme-inhibitor complex as determined by X-ray crystallographic analysis. J. Med. Chem., 2005, 48(15), 4803-4814. []. [PMID: 16033260].
Marchand, C.; Antony, S.; Kohn, K.W.; Cushman, M.; Ioanoviciu, A.; Staker, B.L.; Burgin, A.B.; Stewart, L.; Pommier, Y. A novel norindenoisoquinoline structure reveals a common interfacial inhibitor paradigm for ternary trapping of the topoisomerase I-DNA covalent complex. Mol. Cancer Ther., 2006, 5(2), 287-295. []. [PMID: 16505102].
Hsiang, Y.H.; Lihou, M.G.; Liu, L.F. Arrest of replication forks by drug-stabilized topoisomerase I-DNA cleavable complexes as a mechanism of cell killing by camptothecin. Cancer Res., 1989, 49(18), 5077-5082. [PMID: 2548710].
Potmesil, M.; Kohn, K.W., Eds.; DNA Topoisomerases in Cancer; Oxford University: New York, 1991.
Potmesil, M.; Pinedo, H., Eds.; Camptothecins: New Anticancer Agents; CRC: Boca Raton, 1995.
Houghton, P.J.; Cheshire, P.J.; Myers, L.; Stewart, C.F.; Synold, T.W.; Houghton, J.A. Evaluation of 9-dimethylaminomethyl-10-hydroxycamptothecin against xenografts derived from adult and childhood solid tumors. Cancer Chemother. Pharmacol., 1992, 31(3), 229-239. []. [PMID: 1464161].
a)Kunimoto, T.; Nitta, K.; Tanaka, T.; Uehara, N.; Baba, H.; Takeuchi, M.; Yokokura, T.; Sawada, S.; Miyasaka, T.; Mutai, M. Antitumor activity of 7-ethyl-10-[4-(1-piperidino)-1-piperidino]carbonyloxy-camptothec in, a novel water-soluble derivative of camptothecin, against murine tumors. Cancer Res., 1987, 47(22), 5944-5947. [PMID: 3664496]
b)Catimel, G.; Chabot, G.G.; Guastalla, J.P.; Dumortier, A.; Cote, C.; Engel, C.; Gouyette, A.; Mathieu-Boué, A.; Mahjoubi, M.; Clavel, M. Phase I and pharmacokinetic study of irinotecan (CPT-11) administered daily for three consecutive days every three weeks in patients with advanced solid tumors. Ann. Oncol., 1995, 6(2), 133-140. [] [PMID: 7786821]
c)Chabot, G.G.; Abigerges, D.; Catimel, G.; Culine, S.; de Forni, M.; Extra, J-M.; Mahjoubi, M.; Hérait, P.; Armand, J-P.; Bugat, R.; Clavel, M.; Marty, M.E. Population pharmacokinetics and pharmacodynamics of irinotecan (CPT-11) and active metabolite SN-38 during phase I trials.. Ann. Oncol.., 1995, 6(2), 141-151. [] [PMID: 7786822]
Ahn, S.K.; Choi, N.S.; Jeong, B.S.; Kim, K.K.; Journ, D.J.; Kim, J.K. Practical synthesis of (S)-7-(2-isopropylamino) ethylcamptothecin hydrochloride, potent topoisomerase I inhibitor. J. Heterocycl. Chem., 2000, 37, 1141-1144. [].
van Hattum, A.H.; Pinedo, H.M.; Schlüper, H.M.M.; Erkelens, C.A.M.; Tohgo, A.; Boven, E. The activity profile of the hexacyclic camptothecin derivative DX-8951f in experimental human colon cancer and ovarian cancer. Biochem. Pharmacol., 2002, 64(8), 1267-1277. []. [PMID: 12234607].
Royce, M.E.; Rowinsky, E.K.; Hoff, P.M.; Coyle, J.; DeJager, R.; Pazdur, R.; Saltz, L.B. A phase II study of intravenous exatecan mesylate (DX-8951f) administered daily for five days every three weeks to patients with metastatic adenocarcinoma of the colon or rectum. Invest. New Drugs, 2004, 22(1), 53-61. []. [PMID: 14707494].
Abou-Alfa, G.K.; Letourneau, R.; Harker, G.; Modiano, M.; Hurwitz, H.; Tchekmedyian, N.S.; Feit, K.; Ackerman, J.; De Jager, R.L.; Eckhardt, S.G.; O’Reilly, E.M. Randomized phase III study of exatecan and gemcitabine compared with gemcitabine alone in untreated advanced pancreatic cancer. J. Clin. Oncol., 2006, 24(27), 4441-4447. []. [PMID: 16983112].
Stevenson, J.P.; DeMaria, D.; Sludden, J.; Kaye, S.B.; Paz-Ares, L.; Grochow, L.B.; McDonald, A.; Selinger, K.; Wissel, P.; O’Dwyer, P.J.; Twelves, C. Phase I/pharmacokinetic study of the topoisomerase I inhibitor GG211 administered as a 21-day continuous infusion. Ann. Oncol., 1999, 10(3), 339-344. []. [PMID: 10355580].
Giles, F.J.; Tallman, M.S.; Garcia-Manero, G.; Cortes, J.E.; Thomas, D.A.; Wierda, W.G.; Verstovsek, S.; Hamilton, M.; Barrett, E.; Albitar, M.; Kantarjian, H.M. Phase I and pharmacokinetic study of a low-clearance, unilamellar liposomal formulation of lurtotecan, a topoisomerase 1 inhibitor, in patients with advanced leukemia. Cancer, 2004, 100(7), 1449-1458. []. [PMID: 15042679].
Dong, P.; Zuo, C.; Chen, Z.L.; Gao, Y. Pharmaceutical composition of camptothecin derivative and preparation method thereof. China Patent CN 102764260.A., 2012, (11.7), 76.
Yu, Y.; Zhan, Y.; Chen, X.; Zhang, Y.; Zhong, D. Development and validation of a sensitive LC-MS/MS method for simultaneous quantification of sinotecan and its active metabolite in human blood. J. Chromatogr. B Analyt. Technol. Biomed. Life Sci., 2014, 951-952, 62-68. []. [PMID: 24534567].
Editorial, A. Rubitecan: 9-NC, 9-Nitro-20(S)-camptothecin, 9-nitro-camptothecin, 9-nitrocamptothecin, RFS 2000, RFS2000. Drugs R D., 2004, 5(5), 305-311. []. [PMID: 15357630].
Takimoto, C.H.; Thomas, R. The clinical development of 9-aminocamptothecin. Ann. N. Y. Acad. Sci., 2000, 922, 224-236. []. [PMID: 11193898].
Zou, J.; Li, S.; Chen, Z.; Lu, Z.; Gao, J.; Zou, J.; Lin, X.; Li, Y.; Zhang, C.; Shen, L. A novel oral camptothecin analog, gimatecan, exhibits superior antitumor efficacy than irinotecan toward esophageal squamous cell carcinoma in vitro and in vivo. Cell Death Dis., 2018, 9(6), 661. []. [PMID: 29855512].
Miller, A.A.; Herndon, J.E., II; Gu, L.; Green, M.R. Phase II trial of karenitecin in patients with relapsed or refractory non-small cell lung cancer (CALGB 30004). Lung Cancer, 2005, 48(3), 399-407. []. [PMID: 15893009].
Chen, A.Y.; Shih, S.J.; Garriques, L.N.; Rothenberg, M.L.; Hsiao, M.; Curran, D.P. Silatecan DB-67 is a novel DNA topoisomerase I-targeted radiation sensitizer. Mol. Cancer Ther., 2005, 4(2), 317-324. [PMID: 15713902].
Scott, L.; Soepenberg, O.; Verweij, J.; de Jonge, M.J.; Th Planting, A.S.; McGovern, D.; Principe, P.; Obach, R.; Twelves, C. A multicentre phase I and pharmacokinetic study of BN80915 (diflomotecan) administered daily as a 20-min intravenous infusion for 5 days every 3 weeks to patients with advanced solid tumours. Ann. Oncol., 2007, 18(3), 569-575. []. [PMID: 17322542].
Lavergne, O.; Harnett, J.; Rolland, A.; Lanco, C.; Lesueur-Ginot, L.; Demarquay, D.; Huchet, M.; Coulomb, H.; Bigg, D.C.H. BN 80927: a novel homocamptothecin with inhibitory activities on both topoisomerase I and topoisomerase II. Bioorg. Med. Chem. Lett., 1999, 9(17), 2599-2602. []. [PMID: 10498216].
a)Wani, M.C.; Ronman, P.E.; Lindley, J.T.; Wall, M.E. Plant antitumor agents. 18. Synthesis and biological activity of camptothecin analogues. J. Med. Chem., 1980, 23(5), 554-560. [].[PMID: 7381856]
b)Wani, M.C.; Nicholas, A.W.; Wall, M.E. Plant antitumor agents. 23. Synthesis and antileukemic activity of camptothecin analogues. J. Med. Chem., 1986, 29(11), 2358-2363. [].[PMID: 3783593]
c)Wani, M.C.; Nicholas, A.W.; Manikumar, G.; Wall, M.E. Plant antitumor agents. 25. Total synthesis and antileukemic activity of ring A substituted camptothecin analogues. Structure-activity correlations. J. Med. Chem., 1987, 30(10), 1774-1779. [].[PMID: 3656353]
d)Wall, M.E.; Wani, M.C.; Nicholas, A.W.; Manikumar, G.; Tele, C.; Moore, L.; Truesdale, A.; Leitner, P.; Besterman, J.M. Plant antitumor agents. 30. Synthesis and structure activity of novel camptothecin analogs. J. Med. Chem., 1993, 36(18), 2689-2700. []. [PMID: 8410981].
Yaegashi, T.; Sawada, S.; Nagata, H.; Furuta, T.; Yokokura, T.; Miyasaka, T. Synthesis and antitumor activity of 20(S)-camptothecin derivatives. A-ring-substituted 7-ethylcamptothecins and their E-ring-modified water-soluble derivatives. Chem. Pharm. Bull. (Tokyo), 1994, 42(12), 2518-2525. []. [PMID: 7697767].
a)Kingsbury, W.D.; Boehm, J.C.; Jakas, D.R.; Holden, K.G.; Hecht, S.M.; Gallagher, G.; Caranfa, M.J.; McCabe, F.L.; Faucette, L.F.; Johnson, R.K.; Hertzberg, R.P. Synthesis of water-soluble (aminoalkyl)camptothecin analogues: inhibition of topoisomerase I and antitumor activity. J. Med. Chem., 1991, 34(1), 98-107. [].[PMID: 1846923]
b)Lu, A.J.; Zhang, Z.S.; Zheng, M.Y.; Zou, H.J.; Luo, X.M.; Jiang, H.L. 3D-QSAR study of 20 (S)-camptothecin analogs. Acta Pharmacol. Sin., 2007, 28(2), 307-314. []. [PMID: 17241535].
a)Cheverton, P.; Friess, H.; Andras, C.; Salek, T.; Geddes, C.; Bodoky, G.; Valle, J.; Humblet, Y. Phase III results of exatecan (DX-8951f) versus gemcitabine (Gem) in chemotherapy-naïve patients with advanced pancreatic cancer (APC). J. Clin. Oncol., 2004, 22(14)(Suppl.), 4005. []
b)O’ Reilly, E.M.; Abou-Alfa, G.; Letourneau, K.R.; Harker, W.G.; Modiano, M.; Hurwitz, H.; Tchekmedyian, N.S.; Ackerman, J.; De Jager, R.L.; Eckhardt, S.G. A randomized phase III trial of DX-8951f (Exatecan Mesylate; DX) and Gemcitabine (GEM) vs. Gemcitabine alone in advanced pancreatic cancer (APC). J. Clin. Oncol., 2004, 22(14)(Suppl.), 4006. []
Gao, H.; Zhang, X.; Chen, Y.; Shen, H.; Pang, T.; Sun, J.; Xu, C.; Ding, J.; Li, C.; Lu, W. Synthesis and antitumor activity of the hexacyclic camptothecin derivatives. Bioorg. Med. Chem. Lett., 2005, 15(13), 3233-3236. []. [PMID: 15913996].
Fan, Y.; Shi, L.M.; Kohn, K.W.; Pommier, Y.; Weinstein, J.N. Quantitative structure-antitumor activity relationships of camptothecin analogues: cluster analysis and genetic algorithm-based studies. J. Med. Chem., 2001, 44(20), 3254-3263. []. [PMID: 11563924].
a)Josien, H.; Bom, D.; Curran, D.P.; Zheng, Y-H.; Chou, T-C. 7-Silylcamptothecins (silatecans): A new family of camptothecin antitumor agents. Bioorg. Med. Chem. Lett., 1997, 7, 3189.
b)Bom, D.; Curran, D.P.; Chavan, A.J.; Kruszewski, S.; Zimmer, S.G.; Fraley, K.A.; Burke, T.G.; Novel, A.; Novel, A.B. E-ring-modified camptothecins displaying high lipophilicity and markedly improved human blood stabilities. J. Med. Chem., 1999, 42(16), 3018-3022. [].[PMID: 10447944]
c)Bom, D.; Curran, D.P.; Kruszewski, S.; Zimmer, S.G.; Thompson Strode, J.; Kohlhagen, G.; Du, W.; Chavan, A.J.; Fraley, K.A.; Bingcang, A.L.; Latus, L.J.; Pommier, Y.; Burke, T.G. The novel silatecan 7-tert-butyldimethylsilyl-10-hydroxycamptothecin displays high lipophilicity, improved human blood stability, and potent anticancer activity. J. Med. Chem., 2000, 43(21), 3970-3980. []. [PMID: 11052802].
a)Nicholas, A.W.; Wani, M.C.; Manikumar, G.; Wall, M.E.; Kohn, K.W.; Pommier, Y. Plant antitumor agents. 29. Synthesis and biological activity of ring D and ring E modified analogues of camptothecin. J. Med. Chem., 1990, 33(3), 972-978. []. [PMID: 2155323]
b)Kurihara, T.; Tanno, H.; Takemura, S.; Harusawa, S.; Yoneda, R. Synthesis of C‐nor‐4,6‐secocamptothecin and related compounds. J. Heterocycl. Chem., 1993, 30, 643. [].
a)Subrahmanyam, D.; Venkateswarlu, A.; Venkateswara Rao, K.; Sastry, T.V.; Vandana, G.; Kumar, S.A. Novel C-ring analogues of 20(S)-camptothecin-part-2: synthesis and in vitro cytotoxicity of 5-C-substituted 20(S)-camptothecin analogues. Bioorg. Med. Chem. Lett., 1999, 9(12), 1633-1638. [].[PMID: 10397491]
b)Subrahmanyam, D.; Sarma, V.M.; Venkateswarlu, A.; Sastry, T.V.; Srinivas, A.S.; Krishna, C.V.; Deevi, D.S.; Kumar, S.A.; Babu, M.J.; Damodaran, N.K. Novel C-ring analogues of 20(S)-camptothecin. Part 3: synthesis and their in vitro cytotoxicity of A-, B- and C-ring analogues. Bioorg. Med. Chem. Lett., 2000, 10(4), 369-371. [].[PMID: 10714502]
c)Subrahmanyam, D.; Sarma, V.M.; Venkateswarlu, A.; Sastry, T.V.R.S.; Kulakarni, A.P.; Rao, D.S.; Reddy, K.V.S.R.K. In vitro cytotoxicity of 5-aminosubstituted 20(S)-camptothecins. Part 1. Bioorg. Med. Chem., 1999, 7(9), 2013-2020. [][PMID: 10530950].
d)Chatterjee, A.; Digumarti, R.; Mamidi, R.N.V.S.; Katneni, K.; Upreti, V.V.; Surath, A.; Srinivas, M.L.; Uppalapati, S.; Jiwatani, S.; Subramaniam, S.; Srinivas, N.R. Safety, tolerability, pharmacokinetics, and pharmacodynamics of an orally active novel camptothecin analog, DRF-1042, in refractory cancer patients in a phase I dose escalation study. J. Clin. Pharmacol., 2004, 44(7), 723-736. [].[PMID: 15199077]
e)Samorì, C.; Guerrini, A.; Varchi, G.; Fontana, G.; Bombardelli, E.; Tinelli, S.; Beretta, G.L.; Basili, S.; Moro, S.; Zunino, F.; Battaglia, A. Semisynthesis, biological activity, and molecular modeling studies of C-ring-modified camptothecins. J. Med. Chem., 2009, 52(4), 1029-1039. [] [PMID: 19530720]
a)Cheng, K.; Rahier, N.J.; Eisenhauer, B.M.; Gao, R.; Thomas, S.J.; Hecht, S.M. 14-azacamptothecin: a potent water-soluble topoisomerase I poison. J. Am. Chem. Soc., 2005, 127(3), 838-839. [].[PMID: 15656613]
b)Duan, J.X.; Cai, X.; Meng, F.; Sun, J.D.; Liu, Q.; Jung, D.; Jiao, H.; Matteucci, J.; Jung, B.; Bhupathi, D.; Ahluwalia, D.; Huang, H.; Hart, C.P.; Matteucci, M. 14-Aminocamptothecins: their synthesis, preclinical activity, and potential use for cancer treatment. J. Med. Chem., 2011, 54(6), 1715-1723. []. [PMID: 21341674].
a)Samorì, C.; Guerrini, A.; Varchi, G.; Zunino, F.; Beretta, G.L.; Femoni, C.; Bombardelli, E.; Fontana, G.; Battaglia, A. Thiocamptothecin. J. Med. Chem., 2008, 51(10), 3040-3044. []. [PMID: 18419110]
b)Samorì, C.; Beretta, G.L.; Varchi, G.; Guerrini, A.; Di Micco, S.; Basili, S.; Bifulco, G.; Riccio, R.; Moro, S.; Bombardelli, E.; Zunino, F.; Fontana, G. Structure-activity relationship study of 16 a-thiocamptothecins: an integrated in vitro and in silico approach. ChemMedChem, 2010, 5(12), 2006-2015. []. [PMID: 21069656].
a)Rahier, N.J.; Eisenhauer, B.M.; Gao, R.; Thomas, S.J.; Hecht, S.M. On the role of E-ring oxygen atoms in the binding of camptothecin to the topoisomerase I-DNA covalent binary complex. Bioorg. Med. Chem., 2005, 13(4), 1381-1386. [].[PMID: 15670945]
b)Bailly, C. Homocamptothecins: potent topoisomerase I inhibitors and promising anticancer drugs. Crit. Rev. Oncol. Hematol., 2003, 45(1), 91-108. []. [PMID: 12482574].
a)Omura, S.; Iwai, Y.; Hirano, A.; Nakagawa, A.; Awaya, J.; Tsuchya, H.; Takahashi, Y.; Masuma, R. A new alkaloid AM-2282 OF Streptomyces origin. Taxonomy, fermentation, isolation and preliminary characterization. J. Antibiot. (Tokyo), 1977, 30(4), 275-282. [].[PMID: 863788]
b)Rüegg, U.T.; Burgess, G.M. Staurosporine, K-252 and UCN-01: potent but nonspecific inhibitors of protein kinases. Trends Pharmacol. Sci., 1989, 10(6), 218-220. [].[PMID: 2672462]
c)Funato, N.; Takayanagi, H.; Konda, Y.; Toda, Y.; Harigaya, Y.; Omura, S. Absolute configuration of staurosporine by X-ray analysis. Tetrahedron Lett., 1994, 35(8), 1251-1254. [].
a)Xiao, X-H.; Qou, G-L.; Wang, H-L.; Lui, L-S.; Zheng, Y-L.; Jia, Z-J.; Deng, Z-B. Zhongguo Yaolixue Yu Dulixue Zazhi, 1988, 1(1), 232.
b)Ma, Z.Z.; Hano, Y.; Nomura, T.; Chen, Y-J. Heterocycles., 1997, 46, 541.. [].
c)Cagir, A.; Jones, S.H.; Gao, R.; Eisenhauer, B.M.; Hecht, S.M.; Luotonin, A.A. Luotonin A. A naturally occurring human DNA topoisomerase I poison J. Am. Chem. Soc., 2003, 125(45), 13628.-13629.. [].[PMID: 14599178]
d)Marchand, C.; Antony, S.; Kohn, K.W.; Cushman, M.; Ioanoviciu, A.; Staker, B.L.; Burgin, A.B.; Stewart, L.; Pommier, Y. A novel norindenoisoquinoline structure reveals a common interfacial inhibitor paradigm for ternary trapping of the topoisomerase I-DNA covalent complex Mol. Cancer Ther., 2006, 5(2), 287-295. [] [PMID: 16505102]
e)Lin, L.Z.; Cordell, G.A. Phytochemistry, 1989, 28, 1295-1297.. []
a)Beck, D.E.; Agama, K.; Marchand, C.; Chergui, A.; Pommier, Y.; Cushman, M. Synthesis and biological evaluation of new carbohydrate-substituted indenoiso-quinoline topoisomerase i inhibitors and improved syntheses of the experimental anticancer agents indotecan (LMP400) and indimitecan (LMP776). J. Med. Chem., 2014, 57(4), 1495-1512.
b)Nagarajan, M.; Morrell, A.; Ioanoviciu, A.; Antony, S.; Kohlhagen, G.; Agama, K.; Hollingshead, M.; Pommier, Y.; Cushman, M. Synthesis and evaluation of indenoisoquinoline topoisomerase i inhibitors substituted with nitrogen heterocycles. J. Med. Chem., 2006, 49, 6283-6289.
A phase I study of indenoisoquinolines LMP400 and LMP776 in adults with relapsed solid tumors and lymphomas. (Available at: c)
Indenoisoquinoline LMP744 in adults with relapsed solid tumors and lymphomas. (Available at: d)
a)Prijovich, Z.M.; Burnouf, P-A.; Chou, H-C.; Huang, P-T.; Chen, K-C.; Cheng, T-L.; Leu, Y-L.; Roffler, S.R. Synthesis and antitumor properties of BQC-glucuronide, a camptothecin prodrug for selective tumor activation. Mol. Pharm., 2016, 13(4), 1242-1250. [].[PMID: 26824303]
b)Prijovich, Z.M.; Chen, B-M.; Leu, Y-L.; Chern, J-W.; Roffler, S.R. Anti-tumour activity and toxicity of the new prodrug 9-aminocamptothecin glucuronide (9ACG) in mice. Br. J. Cancer, 2002, 86(10), 1634-1638. []. [PMID: 12085215].
Pantazis, P.; Early, J.A.; Mendoza, J.T.; DeJesus, A.R.; Giovanella, B.C. Cytotoxic efficacy of 9-nitrocamptothecin in the treatment of human malignant melanoma cells in vitro. Cancer Res., 1994, 54(3), 771-776. [PMID: 8306340].
a)Bissett, D.; Cassidy, J.; de Bono, J.S.; Muirhead, F.; Main, M.; Robson, L.; Fraier, D.; Magne, M.L.; Pellizzoni, C.; Porro, M.G.; Spinelli, R.; Speed, W.; Twelves, C. Phase I and pharmacokinetic (PK) study of MAG-CPT (PNU 166148): a polymeric derivative of camptothecin (CPT). Br. J. Cancer, 2004, 91, 50-55.
b)Schoemaker, N.E.; van Kesteren, C.; Rosing, H.; Jansen, S.; Swart, M.; Lieverst, J.; Fraier, D.; Breda, M.; Pellizzoni, C.; Spinelli, R.; Grazia Porro, M.; Beijnen, J.H.; Schellens, J.H.; ten Bokkel Huinink, W.W. A phase I and pharmacokinetic study of MAG-CPT, a water-soluble polymer conjugate of camptothecin. Br. J. Cancer, 2002, 87, 608-614.
c)reenwald R. B.; Pendri A.; Conover C.; Gilbert C.; Yang R.; Xia J. Drug delivery systems. 2. Camptothecin 20-O-poly(ethylene glycol) ester transport forms. J. Med. Chem., 1996, 39, 1938-1940.
d)Posey, J.A. III, Saif M.W.; Carlisle R.; Goetz A.; Rizzo J.; Stevenson S.; Rudoltz M.S.; Kwiatek J.; Simmons P.; Rowinsky E.K.; Takimoto C.H.; Tolcher A.W. Phase 1 study of weekly olyethylene glycol-camptothecin in patients with advanced solid tumors and lymphomas. Clin. Cancer Res., 2005, 11, 7866-7871.
e)Sapra, P.; Mehlig, M.; Malaby, J.; Kraft, P.; Zhang, Z.; Longley, C.; Zhao, H.; Rubio, B.; Wu, D.; Greenberger, L.M.; Horak, I.D. EZN-2208, a novel polyethyleneglycol-SN38 conjugate, has potent antitumor activity in a panel of human tumor xenografts, American Association of Cancer Research Annual Meeting Poster No. 1494; 2007.
f)Schluep, T.; Cheng, J.; Khin, K.; Davis, M. Pharmacokinetics and biodistribution of the camptothecin–polymer conjugate IT-101 in rats and tumor-bearing mice. Cancer Chemother. and Pharmacol., 2006, 57, 654-662.
(g)Schluep, T.; Hwang, J.; Cheng, J.; Heidel, J.D.; Bartlett, D.W.; Hollister, B.; Davis, M.E. Preclinical efficacy of the camptothecin-polymer conjugate IT-101 in multiple cancer models. Clin. Cancer Res., 2006, 12, 1606-1614.
a)Inoue, K.; Kumazawa, E.; Kuga, H.; Susaki, H.; Masubuchi, N.; Kajimura, T. CM-dextran-polyalcohol-camptothecin conjugate: DE-310 with a novel carrier system and its preclinical data. Adv. Exp. Med. Biol., 2003, 519, 145-153. [].[PMID: 12675213]
b)Soepenberg, O.; de Jonge, M.J.A.; Sparreboom, A.; de Bruin, P.; Eskens, F.A.L.M.; de Heus, G.; Wanders, J.; Cheverton, P.; Ducharme, M.P.; Verweij, J. Phase I and pharmacokinetic study of DE-310 in patients with advanced solid tumors. Clin. Cancer Res., 2005, 11(2 Pt 1), 703-711. [PMID: 15701859].
Voss, M.H.; Hussain, A.; Vogelzang, N.; Lee, J.L.; Keam, B.; Rha, S.Y.; Vaishampayan, U.; Harris, W.B.; Richey, S.; Randall, J.M.; Shaffer, D.; Cohn, A.; Crowell, T.; Li, J.; Senderowicz, A.; Stone, E.; Figlin, R.; Motzer, R.J.; Haas, N.B.; Hutson, T. A randomized phase II trial of CRLX101 in combination with bevacizumab versus standard of care in patients with advanced renal cell carcinoma. Ann. Oncol., 2017, 28(11), 2754-2760. []. [PMID: 28950297].
a)Santi, D.V.; Schneider, E.L.; Ashley, G.W. Macromolecular prodrug that provides the irinotecan (CPT-11) active-metabolite SN-38 with ultralong half-life, low C(max), and low glucuronide formation. J. Med. Chem., 2014, 57(6), 2303-2314. [].[PMID: 24494988]
b)A Phase I Study of PLX038 in Patients with Advanced Solid Tumors.
a)Aggarwal, C.; Cohen, R.B.; Yu, E.; Hwang, W-T.; Bauml, J.M.; Alley, E.; Evans, T.L.; Langer, C.J. Etirinotecan pegol (NKTR-102) in third-line treatment of patients with metastatic or recurrent non–small-cell lung cancer: Results of a phase II study. Clin. Lung Cancer, 2018, 19(2), 157-162.
b)Perez, E.A.; Awada, A.; O’Shaughnessy, J.; Rugo, H.S.; Twelves, C. Im S.-A.; Gómez-Pardo P.; Schwartzberg L. S.; Diéras V.; Yardley D. A.; Potter D. A.; Mailliez A.; Moreno-Aspitia A.; Ahn J.-S.; Zhao C.; Hoch U.; Tagliaferri M.; Hannah A. L.; Cortes J. Etirinotecan pegol (NKTR-102) versus treatment of physician’s choice in women with advanced breast cancer previously treated with an anthracycline, a taxane, and capecitabine (BEACON): A randomised, open-label, multicentre, phase 3 trial. Lancet Oncol., 2015, 16(15), 1556-1568. [PMID: 26482278].
a)Ocean, A.J.; Starodub, A.N.; Bardia, A.; Vahdat, L.T.; Isakoff, S.J.; Guarino, M.; Messersmith, W.A.; Picozzi, V.J.; Mayer, I.A.; Wegener, W.A.; Maliakal, P.; Govindan, S.V.; Sharkey, R.M.; Goldenberg, D.M. Sacituzumab govitecan (IMMU‐132), an anti‐Trop‐2‐SN‐38 antibody‐drug conjugate for the treatment of diverse epithelial cancers: Safety and pharmacokinetics. Cancer, 2017, 123, 3843-3854.
b)Cardillo, T.M.; Govindan, S.V.; Sharkey, R.M.; Trisal, P.; Arrojo, R.; Liu, D.; Rossi, E.A.; Chang, C-H., and ; Goldenberg, D.M. Sacituzumab govitecan (IMMU-132), an Anti-Trop-2/SN-38 antibody–drug conjugate: Characterization and efficacy in pancreatic, gastric, and other cancers. Bioconjug. Chem., 2015, 26(5), 919-931. [PMID: 25915780].
Takegawa, N.; Nonagase, Y.; Yonesaka, K.; Sakai, K.; Maenishi, O.; Ogitani, Y.; Tamura, T.; Nishio, K.; Nakagawa, K.; Tsurutani, J. DS-8201a, a new HER2-targeting antibody-drug conjugate incorporating a novel DNA topoisomerase I inhibitor, overcomes HER2-positive gastric cancer T-DM1 resistance. Int. J. Cancer, 2017, 141(8), 1682-1689. [] [PMID: 28677116]
b)Doi, T.; Shitara, K.; Naito, Y.; Shimomura, A.; Fujiwara, Y.; Yonemori, K.; Shimizu, C.; Shimoi, T.; Kuboki, Y.; Matsubara, N.; Kitano, A.; Jikoh, T.; Lee, C.; Fujisaki, Y.; Ogitani, Y.; Yver, A.; Tamura, K. Safety, pharmacokinetics, and antitumour activity of trastuzumab deruxtecan (DS-8201), a HER2-targeting antibody-drug conjugate, in patients with advanced breast and gastric or gastrooesophageal tumours: a phase 1 dose-escalation study. Lancet Oncol., 2017, 18(11), 1512-1522. [] [PMID: 29037983]
c)Iwata, T.N.; Ishii, C.; Ishida, S.; Ogitani, Y.; Wada, T.; Agatsuma, T. A HER2-targeting antibody-drug conjugate, trastuzumab deruxtecan (DS-8201a), enhances antitumor immunity in a mouse model. Mol. Cancer Ther., 2018, 17(7), 1494-1503. [] [PMID: 29703841]

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