Prodrugs for targeted tumor therapies: Recent developments in ADEPT, GDEPT and PMT

Current Pharmaceutical Design

Volumn 17, Issue 32, 2011, Pages 3527-3547

  Tietze, Lutz F ^a   Schmuck, Kianga ^a  

^a UNIVERSITY OF GÖTTINGEN   (Germany)

Author keywords

ADEPT; Cancer; CC 1065; Duocarmycins; GDEPT; Glycosides; PMT; Prodrugs

Indexed keywords

ANTIBIOTIC AGENT; BETA GALACTOSIDASE; BETA GLUCURONIDASE; CAMPTOTHECIN; CYCLOPHOSPHAMIDE; CYCLOPHOSPHAMIDE DERIVATIVE; DAUNORUBICIN; DOCETAXEL; DOXORUBICIN; DUOCARMYCIN DERIVATIVE; DUOCARMYCIN SA; ETOPOSIDE; FLUCYTOSINE; FLUOROURACIL; GANCICLOVIR; GELDANAMYCIN; INDOLEACETIC ACID; MELPHALAN; METHOTREXATE; PACLITAXEL; PRODRUG; PYRROLO[2,1 C][1,4]BENZODIAZEPINE; PYRROLO[2,1 C]BENZODIAZEPINE; PYRROLO[2,1 C]BENZODIAZEPINE GALACTOSIDE; RACHELMYCIN; TRETAZICAR; UNCLASSIFIED DRUG; UNINDEXED DRUG; VINBLASTINE; YATAKEMYCIN; ZD 2767; ZD 2767P;

ADVANCED CANCER; ANTIBODY DIRECTED ENZYME PRODRUG THERAPY; CANCER THERAPY; COLORECTAL CANCER; CYTOTOXICITY; DRUG HALF LIFE; DRUG STRUCTURE; ENZYME PRODRUG THERAPY; GENE DIRECTED ENZYME PRODRUG THERAPY; HUMAN; HYPOXIA; IC 50; MONOTHERAPY; MULTIPLE CYCLE TREATMENT; NONHUMAN; PRIORITY JOURNAL; PRODRUG MONOTHERAPY; REVIEW;

ANIMALS; ANTIBODIES, MONOCLONAL; ANTINEOPLASTIC AGENTS; CELL LINE, TUMOR; CELL SURVIVAL; DRUG DESIGN; GENE THERAPY; HUMANS; MOLECULAR STRUCTURE; NEOPLASMS; PRODRUGS;

EID: 82055176666     PISSN: 13816128     EISSN: 18734286     Source Type: Journal    
DOI: 10.2174/138161211798194459     Document Type: Review

References (171)

1. Kratz F, Müller IA, Ryppa C, Warnecke A. Prodrug Strategies in Anticancer Chemotherapy. ChemMedChem 2008; 3: 20-53.
2. Singh Y, Palombo M, Sinko PJ. Recent trends in targeted anticancer prodrug and conjugate design. Curr Med Chem 2008; 15: 1802-26.
3. Shukla GS; Krag DN. Selective delivery of therapeutic agents for the diagnosis and treatment of cancer. Expert Opin Biol Ther 2006; 6: 39-54.
4. Chari RVJ. Targeted delivery of chemotherapeutics: tumoractivated prodrug therapy. Adv Drug Deliv Rev 1998; 31: 89-104.
5. de Albuquerque Silva AT, Chung MC, Castro LF, Carvalho Güido RV, Ferriera EI. Advances in prodrug design. Mini-Rev Med Chem 2005; 5: 893-914.
6. Fuchs H, Bachran C. Targeted Tumor Therapies at a Glance. Curr Drug Targets 2009; 10: 89-93.
7. Köhler G, Milstein C. Continous cultures of fused cells secreting antibody of predefined specifity. Nature 1975; 256: 495-7.
8. Wilkins DK, Mayer A. Development of antibodies for cancer therapy. Expert Opin Biol Ther 2006; 6: 787-96.
9. Ross JS, Gray K, Schenkein D, et al. Antibody-based therapeutics in oncology. Expert Rev Anticancer Ther 2003; 3: 107-21.
10. Deckert PM. Current Constructs and Targets in Clinical Development for Antibody-Based Cancer Therapy. Curr Drug Targets 2009; 10: 158-75.
11. Brufsky A. Trastuzumab-Based Therapy for Patients With HER2- Positive Breast Cancer: From Early Scientific Development to Foundation of Care. Am J Clin Oncol 2010; 33: 186-95.
12. Slamon DJ, Clark GM, Wong SG, Levin WJ, Ulrich A, McGuire WL. Human breast cancer: correlation of relapse and survival with the amplification of the HER-2/neu oncogene. Science 1987; 235: 177-82.
13. Cortes-Funes H. The role of antiangiogenesis therapy: Bevacizumab and beyond. Clin Transl Oncol 2009; 11: 349-55.
14. Ducry L, Stump B. Antibody-Drug Conjugates: Linking Cytotoxic Payloads to Monoclonal Antibodies. Bioconjugate Chem 2010; 21: 5-13.
15. Lambert JM. Drug-conjugated monoclonal antibodies for the treatment of cancer. Curr Opin Pharmacol 2005; 5: 543-9.
16. Hughes B. Antibody-drug conjugates for cancer: poised to deliver? Nat Rev Drug Discovery 2010; 9: 665-7.
17. Hamann PR. Monoclonal antibody-drug conjugates. Expert Opin Ther Patents 2005; 15: 1087-103.
18. McGavin JK, Spencer CM. Gemtuzumab ozogamicin. Drugs 2001; 61: 1317-22.
19. Krop IE, Beeram M, Modi S, et al. Phase I Study of Trastuzumab- DM1, an HER2 Antibody-Drug Conjugate, Given Every 3 Weeks to Patients With HER2-Positive Metastatic Breast Cancer. J Clin Oncol 2010; 28: 2698-704.
20. Herbertson RA, Tebbutt NC, Lee F-T, et al. Phase I Biodistribution and Pharmacokinetic Study of Lewis Y-Targeting Immunoconjugate CMD-193 in Patients with Advanced Epithelial Cancers. Clin Cancer Res 2009; 15: 6709-15.
21. Bagshawe KD. Antibody directed enzymes revive anti-cancer prodrugs concept. Br J Cancer 1987; 56: 531-2.
22. [Tietze LF, Glüsenkamp K-H. unpublished work.
23. Bagshawe KD. Antibody-directed enzyme prodrug therapy (ADEPT) for cancer. Expert Rev Anticancer Ther 2006; 6: 1421-31.
24. Bagshawe KD. Targeting: The ADEPT Story So Far. Curr Drug Targets 2009; 10: 152-7.
25. Bagshawe KD, Sharma SK, Begent RHJ. Antibody-directed enzyme prodrug therapy (ADEPT) for cancer. Expert Opin Biol Ther 2004; 4: 1777-89.
26. Napier MP, Sharma SK, Springer CJ, et al. Antibody-directed Enzyme Prodrug Therapy: Efficacy and Mechanism of Action in Colorectal Carcinoma. Clin Cancer Res 2000; 6: 765-72.
27. Sharma SK, Pedley RB, Bhatia J, et al. Sustained Tumor Regression of Human Colorectal Cancer Xenografts Using a Multifunctional Mannosylated Fusion Protein in Antibody-Directed Enzyme Prodrug Therapy. Clin Cancer Res 2005; 11: 814-25.
28. Cheng TL, Wei SL, Chern BM, Wu MF, Liu PW, Roffler SR. Bystander killing of tumour cells by antibody-targeted enzymatic activation of a glucuronide prodrug. Br J Cancer 1999; 79: 1378-85.
29. Xu G, McLeod HL. Strategies for enzyme/prodrug cancer therapy. Clin Cancer Res 2001; 7: 3314-24.
30. Niculescu-Duvaz I, Springer CJ. Antibody-directed enzyme prodrug therapy (ADEPT): a review. Adv Drug Delivery Rev 1997; 26: 151-72.
31. Tietze LF, Feuerstein T. Enzyme and Proton-Activated Prodrugs for a Selective Cancer Therapy. Curr Pharm Des 2003; 9: 2155-75.
32. Tietze LF, Herzig T, Feuerstein T, Schuberth I. Synthesis and Biological Evaluation of Novel Analogues and Prodrugs of the Cytotoxic Antibiotic CC-1065 for Selective Cancer Therapy. Eur J Org Chem 2002; 2002: 1634-45.
33. Wentworth P, Datta A, Blakey D, Boyle T, Partridge LJ, Blackburn GM. Toward antibody-directed abzyme prodrug therapy, ADAPT: carbamate prodrug activation by a catalytic antibody and its in vitro application to human tumor cell killing. Proc Natl Acad Sci USA 1996; 93: 799-803.
34. Shabat D, Rader C, List B, Lerner RA, Barbas III CF. Multiple event activation of a generic prodrug trigger by antibody catalysis. Proc Natl Acad Sci USA 1999; 96: 6925-30.
35. Houston TA. Painting the Target Around the Arrow: Two-Step Prodrug Therapies from a Carbohydrate Chemist's Perspective. Curr Drug Delivery 2007; 4: 264-8.
36. Altaner C. Prodrug cancer gene therapy. Cancer Lett 2008; 270: 191-201.
37. Schepelmann S, Niculescu-Duvaz I, Springer CJ. Suicide Gene Therapy. In: Bronchud MH, Foote MA, Giaccone G, Olopade O, Workman P, Eds. Principles of Molecular Oncology. Totowa, NJ: Humana Press Inc. 2008; pp. 367-82.
38. Schepelmann S, Springer CJ. Viral Vectors for Gene-Directed Enzyme Prodrug Therapy. Curr Gene Ther 2006; 6: 647-70.
39. Vaha-Koskela MJ, Heikkila JE, Hinkkanen AE. Oncolytic viruses in cancer therapy. Cancer Lett 2007; 254: 178-216.
40. Pesonen S, Kangasniemi L, Hemminki A. Oncolytic adenoviruses for the treatment of human cancer: ocus on translational and clinical data. Mol Pharmaceutics 2011; 8: 12-28
41. Fillat C, Carrio M, Cascante A, Sangro B. Suicide Gene Therapy Mediated by the Herpes Simplex Virus Thymidine Kinase Gene/Ganciclovir System: Fifteen Years of Application. Curr Gene Ther 2003; 3, 13-26.
42. Dalba C, Bellier B, Kasahara N, Klatzmann D. Replicationcompetent Vectors and Empty Virus-like Particles: New Retroviral Vector Designs for Cancer Gene Therapy or Vaccines. Mol Ther 2007; 15: 457-66.
43. Seubert CM, Stritzker J, Hess M, et al. Enhanced tumor therapy using vaccinia virus strain GLV-1h68 in combination with a β- galactosidase-activatable prodrug seco-analog of duocarmycin SA. Cancer Gene Ther 2011; 18: 42-52.
44. Schatzlein, A. G. Non-viral vectors in cancer gene therapy: principles and progress. Anti-Cancer Drugs 2001; 12: 275-304.
45. Hickman MA, Malone RW, Lehmann-Bruinsma K, et al. Gene Expression Following Direct Injection of DNA into Liver. Hum Gene Ther 1994; 5: 1477-83.
46. Miller AD. Cationic Liposomes for Gene Therapy. Angew Chem Int Ed 1998; 37:1768-85.
47. Liu T, Zhang G, Chen YH, et al. Tissue specific expression of suicide genes delivered by nanoparticles inhibits gastric carcinoma growth. Cancer Biol Ther 2006; 5: 1683-90.
48. Duncan R, Gac-Breton S, Keane R, et al. Polymer-drug conjugates, polymer-directed enzyme prodrug therapy (PDEPT) and (polymerenzyme liposome therapy) PELT: basic principles for design and transfer from the laboratory to clinic. J Control Release 2001; 74: 135-46.
49. Minton NP. Clostridia in cancer therapy. Nat Rev Microbiol 2003; 1: 237-42.
50. Patyar S, Joshi R, Prasad Byrav DS, Prakash A, Medhi B, Das BK. Bacteria in cancer therapy: a novel experimental strategy. J Biomed Sci 2010; 17: 21.
51. Zhang Q, Xiang G, Zhang Y, et al. Increase of doxorubicin sensitivity for folate receptor positive cells when given as the prodrug N-(phenylacetyl) doxorubicin in combination with folateconjugated PGA. J Pharm Sci 2006; 95: 2266-75.
52. Robinson MA, Charlton ST, Garnier P, et al. LEAPT: Lectindirected enzyme-activated prodrug therapy. Proc Natl Acad Sci USA 2004; 101: 14527-32.
53. De Groot FMH, Damen EWP, Scheeren HW. Anticancer Prodrugs for Application in Monotherapy Targeting Hypoxia, Tumor- Associated Enzymes, and Receptors. Curr Med Chem 2001; 8: 1093-122.
54. Denny WA. Tumor-activated Prodrugs - A New Approach to Cancer Therapy. Cancer Invest 2004; 22: 604-19.
55. Martin J, Stribbling SM, Poon GK, et al. Antibody-directed enzyme prodrug therapy: pharmacokinetics and plasma levels of prodrug and drug in a phase I clinical trial. Cancer Chemother Pharmacol 1997; 40: 189-201.
56. Monks NR, Blakey DC, East SJ, Dowell RI, Calvete JA, Curtin NJ. DNA interstrand cross-linking and TP53 status as determinants of tumour cell sensitivity in vitro to the antibody-directed enzyme prodrug therapy ZD2767. Eur J Cancer 2002; 38: 1543-52.
57. Mayer A, Francis RJ, Sharma SK, et al. A Phase I Study of Single Administration of Antibody-Directed Enzyme Prodrug Therapy with the Recombinant Anti-Carcinoembryonic Antigen Antibody- Enzyme Fusion Protein MFECP1 and a Bis-Iodo Phenol Mustard Prodrug. Clin Cancer Res 2006; 12: 6509-16.
58. Wallace PM, Senter PD. In vitro and in vivo activities of monoclonal antibody-alkaline phosphatase conjugates in combination with phenol mustard phosphate. Bioconjugate Chem 1991; 2: 349-52.
59. Svensson HP, Kadow JF, Vrudhula VM, Wallace PM, Senter PD. Monoclonal antibody-??-lactamase conjugates for the activation of a cephalosporin mustard prodrug. Bioconjugate Chem 1992; 3: 176-81.
60. Smal MA, Dong Z, Cheung HT, et al. Activation and cytotoxicity of 2-α-aminoacyl prodrugs of methotrexate. Biochem Pharmacol 1995; 49: 567-74.
61. Deckert PM, Bornmann WG, Ritter G, et al. Specific tumour localisation of a huA33 antibody: carboxypeptidase A conjugate and activation of methotrexate-phenylalanine. Int J Oncol 2004; 24: 1289-95.
62. Florent JC, Monneret C. Doxorubicin Conjugates for Selective Delivery to Tumors. Top Curr Chem 2008; 283: 99-140.
63. Florent JC, Dong X, Gaudel G, et al. Prodrugs of anthracyclines for use in antibody-directed enzyme prodrug therapy. J Med Chem 1998; 41: 3572-81.
64. Senter PD, Su PCD, Katsuragi T, et al. Generation of 5-fluorouracil from 5-fluorocytosine by monoclonal antibody-cytosine deaminase conjugates. Bioconjugate Chem 1991; 2: 447-51.
65. Senter PD, Saulnier MG, Schreiber GJ, et al. Anti-Tumor Effects of Antibody-Alkaline Phosphatase Conjugates in Combination with Etoposide Phosphate. Proc Natl Acad Sci USA 1988; 85: 4842-6.
66. Jungheim LN, Shepherd TA, Meyer DL. Synthesis of acylhydrazido- substituted cephems. Design of cephalosporin-vinca alkaloid prodrugs: substrates for an antibody targeted enzyme. J Org Chem 1992; 57: 2334-40.
67. Rodrigues ML, Carter P, Wirth C, Mullins S, Lee A, Blackburn BK. Synthesis and β-lactamase-mediated activation of a cephalosporin- taxol prodrug. Chem Biol 1995; 2: 223-7.
68. Pessah N, Reznik M, Shamis M, et al. Bioactivation of carbamatebased 20(S)-camptothecin prodrugs. Bioorg Med Chem 2004; 12: 1859-66.
69. Frei E III, Teicher BA, Holden SA, Cathcart KNS, Wang Y. Preclinical Studies and Clinical Correlation of the Effect of Alkylating Dose. Cancer Res 1988; 48: 6417-23.
70. Martin DG, Biles C, Gerpheide SA, et al. CC-1065 (NSC 298223), a potent new antitumor agent improved production and isolation, characterization and antitumor activity. J Antibiot 1981; 34: 1119-25.
71. Ichimura M, Ogawa T, Takahashi K, et al. Duocarmycin, a new antitumor antibiotic from streptomyces sp. J Antibiot 1990; 43: 1037-8.
72. Igarashi Y, Futamata K, Fujita T, et al. Yatakemycin, a novel antifungal antibiotic produced by Streptomyces sp. TP-A0356. J Antibiot 2003; 56: 107-13.
73. Teicher BA, Frei E. Development of alkylating agent-resistant human tumor cell lines. Cancer Chemother Pharmacol 1988; 21: 292-8.
74. Baraldi PG, Bovero A, Fruttarolo F, et al. DNA minor groove binders as potential antitumor and antimicrobial agents. Med Res Rev 2004; 24: 475-528.
75. Cacciari B, Romagnoli R, Baraldi PG, Da Ros T, Spalluto G. CC-1065 and the duocarmycins: recent developments. Exp Opin Ther Pat 2000; 10: 1853-71.
76. Nagamura S, Asai A, Kobayashi E, Gomi K, Saito H. Studies on duocarmycin SA and its derivatives. Bioorg Med Chem 1997; 5: 623-30.
77. McGovern JP, Clarke GL, Pratt EA, deKoning TF. Preliminary toxicity studies with the DNA-binding antibiotic CC-1065. J Antibiot 1984; 37: 63-70.
78. Foster BJ, LoRusso PM, Poplin E, et al. Phase I trial of Adozelesin using the treatment schedule of daily x 5 every 3 weeks. Invest New Drugs 1995; 13: 321-6.
79. Awada A, Punt CJA, Piccart MJ, et al. Phase I study of Carzelesin (U-80,244) given (4-weekly) by intravenous bolus schedule. Brit J Cancer 1999; 79: 1454-61.
80. Volpe DA, Tomaszewski JE, Parchment RE, et al. Myelotoxic effects of the bifunctional alkylating agent bizelesin on human, canine and murine myeloid progenitor cells. Cancer Chemother Pharm 1996; 39: 143-9.
81. Tietze LF, Krewer B. Novel Analogues of CC-1065 and the Duocarmycins for the Use in Targeted Tumour Therapies. Anti-Cancer Agents Med Chem 2009; 9: 304-25.
82. Tietze LF, Krewer B. Antibody-Directed Enzyme Prodrug Therapy: A Promising Approach for a Selective Treatment of Cancer Based on Prodrugs and Monoclonal Antibodies. Chem Biol Drug Des 2009; 74: 205-11.
83. Tietze LF, Feuerstein T. Review: Highly Selective Compounds for the Antibody-Directed Enzyme Prodrug Therapy of Cancer. Aust J Chem 2003; 56: 841-54.
84. Ghosh N, Sheldrake HM, Searcey M, Pors K. Chemical and Biological Explorations of the Family of CC-1065 and the Duocarmycin Natural Products. Curr Top Med Chem 2009; 9: 1494-524.
85. [Hurley LH, Lee CS, McGovren JP, et al. Molecular basis for sequence- specific DNA alkylation by CC-1065. Biochemistry 1988; 27: 3886-92.
86. Boger DL, Johnson DS. CC-1065 and the duocarmycins: understanding their biological function through mechanistic studies. Angew Chem Int Ed 1996; 35: 1438-74.
87. --3 Participation. Isolation and Behavior of Spiro(2,5)octa-1,4-diene-3-one. J Am Chem Soc 1963; 85: 567-78.
88. Boger DL, Takayoshi I, Wysocki Jr. RJ, Munk SA, Kitos PA, Suntornwat O. Total synthesis and evaluation of (±)-N-(tertbutoxycarbonyl)- CBI, (±)-CBI-CDPI1, and (±)-CBI-CDPI2: CC-1065 functional agents incorporating the equivalent 1,2,9,9atetrahydrocyclopropa[1,2-c]benz[1,2-e]indol-4-one (CBI) left-hand subunit. J Am Chem Soc 1989; 111: 6461-3
89. Tietze LF, von Hof JM, Krewer B, et al. Asymmetric Synthesis and Biological Evaluation of New Glycosidic Prodrugs for a Selective Cancer Therapy. ChemMedChem 2008; 3: 1946-55.
90. Tietze LF, Herzig T, Fecher A, Haunert F, Schuberth I. Highly Selective Glycosylated Prodrugs of Cytostatic CC-1065 Analogues for Antibody-Directed Enzyme Tumor Therapy. ChemBioChem 2001; 2: 758-65.
91. Tietze LF, Schuster HJ, Hampel SM, Rühl S, Pfoh R. Enantio- and Diastereoselective Synthesis of Duocarmycine-Based Prodrugs for a Selective Treatment of Cancer by Epoxide Opening. Chem Eur J 2008; 14: 895-901.
92. Tietze LF, Major F, Schuberth I. Antitumor Agents: Development of Highly Potent Glycosidic Duocarmycin Analogues for Selective Cancer Therapy. Angew Chem Int Ed 2006; 45: 6574-7.
93. Tietze LF, Major F, Schuberth I, et al. Selective Treatment of Cancer: Synthesis, Biological Evaluation and Structural Elucidation of Novel Analogues of the Antibiotic CC-1065 and the Duocarmycins. Chem Eur J 2007; 13: 4396-409.
94. Tietze LF, Feuerstein T, Fecher A, et al. Proof of Principle in the Selective Treatment of Cancer by Antibody Directed Enzyme Prodrug Therapy. The Development of a Highly Potent Prodrug. Angew Chem Int Ed 2002; 41: 759-61.
95. Tietze LF, Lieb M, Herzig T, Haunert F, Schuberth I. A Strategy for Tumor-Selective Chemotherapy by Enzymatic Liberation of seco-Duocarmycin SA-Derivatives from Non-toxic Prodrugs. Bioorg Med Chem 2001; 9: 1929-39.
96. Schmidt RR. New Methods for the Synthesis of Glycosides and Oligosaccharides - Are There Alternatives to the Koenigs-Knorr Method? Angew Chem Int Ed 1986; 25: 212-35.
97. Tietze LF, Schmuck K, Schuster HJ, Müller M, Schuberth I. Synthesis and Biological Evaluation of Prodrugs Based on the Natural Antibiotic Duocarmycin for Use in ADEPT and PMT. Chem Eur J 2011; 17: 1922-9.
98. Tietze LF, Schuster HJ, Krewer B, Schuberth I. Synthesis and Biological Studies of Different Duocarmycin based Glycosidic Prodrugs for their use in Antibody-Directed Enzyme Prodrug Therapy. J Med Chem 2009; 52: 537-43.
99. Milbank JBJ, Tercel M, Atwell GJ, Wilson WR, Hogg A, Denny WA. Synthesis of 1-substituted 3-(chloromethyl)-6-aminoindoline (6-amino-seco-CI) DNA minor groove alkylating agents and structure- activity relationships for their cytotoxicity. J Med Chem 1999; 42: 649-58.
100. Bont DBA, Leenders RGG, Haisma HJ, van der Meulen-Muileman I, Scheeren HW. Synthesis and biological activity of β-glucuronyl carbamate-based prodrugs of paclitaxel as potential candidates for ADEPT. Bioorg Med Chem 1997; 5: 405-14.
101. ® (paclitaxel) prodrugs designed for ADEPT and PMT strategies in cancer chemotherapy. Bioorg Med Chem 2006; 14: 5012-9.
102. Schuster HJ, Krewer B, von Hof JM, et al. Synthesis of the first spacer containing prodrug of a duocarmycin analogue and determination of its biological activity. Org Biomol Chem 2010; 8: 1833-1842.
103. Tietze LF, von Hof JM, Müller M, Krewer B, Schuberth I. Glycosidic Prodrugs of Highly Potent Bifunctional Duocarmycin Derivatives for Selective Treatment of Cancer. Angew Chem Int Ed 2010; 49: 7336-9.
104. Sharma SK, Jia G, Lown JW. Novel Cyclopropylindole Conjugates and Dimers Synthesis and Anti-Cancer Evaluation. Curr Med Chem Anti Canc Agents 2001; 1: 27-45.
105. Rahman KM, Thompson AS, James CH, Narayanaswarmy M, Thurston DE. The Pyrrolobenzodiazepine Dimer SJG-136 Forms Sequence-Dependent Intrastrand DNA Cross-Links and Monoalkylated Adducts in Addition to Interstrand Cross-Links. J Am Chem Soc 2009; 131: 13756-66.
106. Sagnou MJ, Howard PW, Gregson SJ, Eno-Amooquaye E, Burke PJ, Thurston DE. Design and synthesis of novel pyrrolobenzodiazepine (PBD) prodrugs for ADEPT and GDEPT. Bioorg Med Chem Lett 2000; 10: 2083-6.
107. Masterson LA, Spanswick VJ, Hartley JA, Begent RH, Howard PW, Thurston DE. Synthesis and biological evaluation of novel pyrrolo[2,1-c][1,4]benzodiazepine prodrugs for use in antibodydirected enzyme prodrug therapy. Bioorg Med Chem Lett 2006; 16: 252-6.
108. Kamal A, Tekumalla V, Krishnan A, Pal-Bhadra M, Bhadra U. Development of Pyrrolo[2,1-c][1,4]benzodiazepine β-Galactoside Prodrugs for Selective Therapy of Cancer by ADEPT and PMT. ChemMedChem 2008; 3: 794-802.
109. Torgov MY, Alley SC, Cerveny CG, Farquhar D, Senter PD. Generation of an Intensely Potent Anthracycline by a Monoclonal Antibody-β-Galactosidase Conjugate. Bioconjugate Chem 2005; 16: 717-21.
110. Devalapally H, Navath RS, Yenamandra V, Akkinepally RR, Devarakonda RK. β-galactoside prodrugs of doxorubicin for application in antibody directed enzyme prodrug therapy/prodrug mono therapy. Arch Pharm Res 2007; 30: 723-32.
111. Heinis C, Alessi P, Neri D. Engineering a Thermostable Human Prolyl Endopeptidase for Antibody-Directed Enzyme Prodrug Therapy. Biochemistry 2004; 43: 6293-303.
112. Cheng H, Cao X, Xian M, et al. Synthesis and Enzyme-Specific Activation of Carbohydrate-Geldanamycin Conjugates with Potent Anticancer Activity. J Med Chem 2005; 48: 645-52.
113. Wang Y, Yuan H, Wright SC, Wang H, Larrick JW. Synthesis and preliminary cytotoxicity study of a cephalosporin-CC-1065 analogue prodrug. BMC Chem Biol 2001; 1: 4.
114. Shabat D. Self-immolative dendrimers as novel drug delivery platforms. J Polym Sci, Part A: Polym Chem 2006; 44: 1569-78.
115. Dachs GU, Tupper J, Tozer GM. From bench to bedside for genedirected enzyme prodrug therapy of cancer. Anti-Cancer Drugs 2005; 16: 349-59.
116. Niculescu-Duvaz I, Springer CJ. Introduction to the Background, Principles, and State of the Art in Suicide Gene Therapy. Mol Biotechnol 2005; 30: 71-88.
117. Niculescu-Duvaz D, Niculescu-Duvaz I, Springer CJ. Design of Prodrugs for Suicide Gene Therapy. Methods Mol Med 2004; 90: 161-202.
118. Riddick DS, Lee C, Ramji S, et al. Cancer chemotherapy and drug metabolism. Drug Metab Dispos 2005; 33: 1083-96.
119. Portsmouth D, Hlavaty J, Renner M. Suicide genes for cancer therapy. Mol Aspects Med 2007; 28: 4-41.
120. Hedley D, Ogilvie L, Springer C. Carboxypeptidase G2-based gene-directed enzyme-prodrug therapy: a new weapon in the GDEPT armoury. Nat Rev Cancer 2007; 7: 870-9.
121. Kan O, Kingsman S, Naylor S. Cytochrome P450-based cancer gene therapy: current status. Expert Opin Biol Ther 2002; 2: 857-68.
122. Wrasidlo W, Johnson DS, Boger DL. Induction of endonucleolytic DNA fragmentation and apoptosis by the duocarmycins. Bioorg Med Chem Lett 1994; 4: 631-6.
123. Denny WA. Prodrugs for Gene-Directed Enzyme-Prodrug Therapy (Suicide Gene Therapy). J Biomed Biotech 2003; 1: 48-70.
124. Hay MP, Sykes BM, Denny WA, Wilson WR. A 2-nitroimidazole carbamate prodrug of 5-amino-1-(chloromethyl)-3-[5,6,7- trimethoxyindol-2-yl)carbonyl]-1,2-dihydro-3H-benz[e]indole (amino-seco-CBI-TMI) for use with ADEPT and GDEPT. Bioorg Med Chem Lett 1999; 9: 2237-42.
125. Hay MP, Atwell GJ, Wilson WR, Pullen SM, Denny WA. Structure- activity relationship for 4-nitrobenzyl carbamates of 5- aminobenz[e]indoline minor groove alkylating agents as prodrug for GDEPT in conjugation with E. coli nitroreductase. J Med Chem 2003; 46: 2456-66.
126. Zhang X, Lin Y, Gillies RJ. Tumor pH and Its Measurement. J Nucl Med 2010; 51: 1167-70.
127. Gillies RJ, Robey I, Gatenby RA. Causes and Consequences of Increased Glucose Metabolism of Cancers. J Nucl Med 2008; 49: 24S-42S.
128. Tietze LF, Fischer R. Stereoselective synthesis of β-glucosides with 1,1'-diacetal structure. Angew Chem Int Ed 1981; 20: 969-70.
129. Tietze LF. Konzepte für eine selektive Chemotherapie maligner Tumoren. Nachr Chem Tech Lab 1988; 36: 728-37.
130. Tietze LF, Beller M. Development of selective anticancer agents. Synthesis of acetal β-glucosides from cytotoxic alcohols. Liebigs Ann Chem 1990; 6: 587-91.
131. Tietze LF, Beller M, Fischer R, et al. Development of custommade, acid-catalytically activatable cytostatics for selective tumor therapy. Angew Chem Int Ed 1990; 29: 782-3.
132. Kratz, Felix. Acid-sensitive prodrugs of doxorubicin. Top Curr Chem 2008; 283: 73-97.
133. Tietze LF, Panknin O, Major F, Krewer B. Synthesis of a novel pentagastrin-drug conjugate for a targeted tumor therapy. Chem Eur J 2008; 14: 2811-8.
134. Tietze LF, Panknin O, Krewer B, Major F, Schuberth I. Synthesis and Biological Evaluation of a Novel Pentagastrin-Toxin Conjugate Designed for a Targeted Prodrug Monotherapy of Cancer. Int J Mol Sci 2008; 9: 821-37.
135. Connors TA, Whisson ME. Cure of Mice bearing Advanced Plasma Cell Tumours with Aniline Mustard: the Relationship between Glucuronidase Activity and Tumour Sensitivity. Nature 1966; 210: 866-7.
136. Bosslet K, Straub R, Blumrich M, et al. Elucidation of the mechanism enabling tumor selective prodrug monotherapy. Cancer Res 1998; 58: 1195-201.
137. Sinhababu A, Thakker D. Prodrugs of anticancer agents. Adv Drug Deliv Rev 1996; 19: 241-73.
138. Mürdter TE, Friedel G, Backmann JT, et al. Dose optimization of a doxorubicin prodrug (HMR 1826) in isolated perfused human lungs: low tumor pH promotes prodrug activation by β- glucuronidase. J Pharmacol Exp Ther 2002; 301: 223-8.
139. Tietze LF, Seele R, Leiting B, Krach T. Stereoselective synthesis of (1-alkoxyalkyl) α- and β-D-glucopyranosiduronates (acetalglucopyranosiduronates): a new approach to specific cytostatics for the treatment of cancer. Carbohydr Res 1988; 180: 253-62.
140. [Bosslet K, Czech J, Hoffmann D. A novel one-step tumor-selective prodrug activation. Tumor Target 1995; 1: 45-50.
141. de Graaf M, Boven E, Scheeren HW, Haisma HJ, Pinedo HM. Beta-Glucuronidase-Mediated Drug Release. Curr Pharm Des 2002; 8: 1391-403.
142. Chen X, Wu B, Wang PG. Glucuronides in Anti-Cancer Therapy. Curr Med Chem Anti Canc Agents 2003; 3: 139-50.
143. Brüsselbach S. Extracellular β-Glucuronidase for Gene-Directed Enzyme-Prodrug Therapy. Methods Mol Med 2004; 90: 303-30.
144. Weyel D, Sedlacek H-H, Müller R, Brüsselbach S. Secreted human β-glucuronidase: a novel tool for gene-directed enzyme prodrug therapy. Gene Ther 2000; 7: 224-31.
145. Houba PHJ, Boven E, van der Meulen-Muileman IH, et al. Pronounced antitumor efficacy of doxorubicin when given as the prodrug DOX-GA3 in combination with a monoclonal antibody β- glucuronidase conjugate. Int J Cancer 2001; 91: 550-4.
146. de Graaf M, Pinedo HM, Oosterhoff D, et al. Pronounced Antitumor Efficacy by Extracellular Activation of a Doxorubicin- Glucuronide Prodrug After Adenoviral Vector-Mediated Expression of a Human Antibody-Enzyme Fusion Protein. Hum Gene Ther 2004; 15: 229-38.
147. de Graaf M, Nevalainen TJ, Scheeren HW, Pinedo HM, Haisma HJ, Boven E. A methylester of the glucuronide prodrug DOX-GA3 for improvement of tumor-selective chemotherapy. Biochem Pharmacol 2004; 68: 2273-81.
148. Leu YL, Chen CS, Wu YJ, Chern J-W. Benzyl Ether-Linked Glucuronide Derivative of 10-Hydroxycamptothecin Designed for Selective Camptothecin-Based Anticancer Therapy. J Med Chem 2008; 51: 1740-6.
149. Angenault S, Thirot S, Schmidt F, Monneret C, Pfeiffer B, Renard P. Cancer chemotherapy: A SN-38 (7-Ethyl-10-hydroxycamptothecin) glucuronide prodrug for treatment by a PMT (Prodrug monoTherapy) strategy. Bioorg Med Chem Lett 2003; 13: 947-50.
150. Prijovich ZM, Chen B-M, Leu Y-L, Chern J-W, Roffler SR. Antitumour activity and toxicity of the new prodrug 9-aminocamptothecin glucuronide (9ACG) in mice. Brit J Cancer 2002; 86: 1634-8.
151. Prijovich ZM, Leu Y-L, Roffler SR. Effect of pH and human serum albumin on the cytotoxicity of a glucuronide prodrug of 9- aminocamptothecin. Cancer Chemother Pharmacol 2007; 60: 7-17.
152. Schmidt F, Ungureanu I, Duval R, Pompon A, Monneret C. Cancer Chemotherapy: A Paclitaxel Prodrug for ADEPT (Antibody- Directed Enzyme Prodrug Therapy). Eur J Org Chem 2001; 2001: 2129-34.
153. Bouvier E, Thirot S, Schmidt F, Monneret C. A new paclitaxel prodrug for use in ADEPT strategy. Org Biomol Chem 2003; 1: 3343-52.
154. Bouvier E, Thirot S, Schmidt F, Monneret C. First enzymatically activated Taxotere prodrugs designed for ADEPT and PMT. Bioorg Med Chem 2004; 12: 969-77.
155. Schmidt F, Monneret C. Prodrug Mono Therapy: Synthesis and Biological Evaluation of an Etoposide Glucuronide-Prodrug. Bioorg Med Chem 2003, 11: 2277-83.
156. Kamal A, Tekumalla V, Raju P, Naidu VGM, Diwan PV, Sistla R. Pyrrolo[2,1-c][1,4]benzodiazepine-β-glucuronide prodrugs with a potential for selective therapy of solid tumors by PMT and ADEPT strategies. Bioorg Med Chem Lett 2008; 18: 3769-73.
157. Wang Y, Yuan H, Wright SC, Wang H, Larrick J.W. Synthesis and preliminary cytotoxicity study of glucuronide derivatives of CC-1065 analogues. Bioorg Med Chem 2003; 11: 1569-75.
158. Wang Y, Wright SC, Larrick JW, inventors; Panorama Research Inc., assignee. DNA-binding indole derivatives, their prodrugs and immunoconjugates. United States Patent US5843937. 1998 Dec.
159. Tietze LF, Schuster HJ, Schmuck K, Schuberth I, Alves F. Duocarmycin- based prodrugs for cancer prodrug monotherapy. Bioorg Med Chem 2008; 16: 6312-8.
160. Devy L, de Groot FMH, Blacher S, et al. Plasmin-activated doxorubicin prodrugs containing a spacer reduce tumor growth and angiogenesis without systemic toxicity. FASEB J 2004; 18: 565-7.
161. de Groot FMH, de Bart ACW, Verheijen JH, Scheeren HW. Synthesis and Biological Evaluation of Novel Prodrugs of Anthracyclines for Selective Activation by the Tumor-Associated Protease Plasmin. J Med Chem 1999; 42: 5277-83.
162. Bielawski K, Bielawska A. Small-Molecule based Delivery Systems for Alkylating Antineoplastic Compounds. ChemMedChem 2008; 3: 536-42.
163. Brown JM, Wilson WR. Exploiting tumor hypoxia in cancer treatment. Nat Rev Cancer 2004; 4: 437-47.
164. Chen Y, Hu L. Design of Anticancer Prodrugs for Reductive Activation. Med Res Rev 2009; 29: 29-64.
165. Binley K, Askham Z, Martin L, et al. Hypoxia-mediated tumour targeting. Gene Ther 2003; 10: 540-9.
166. Wilson WR, Stribbling SM, Pruijn FB, et al. Nitrochloromethylbenzindolines: hypoxia-activated prodrugs of potent adenine N3 DNA minor groove alkylators. Mol Cancer Ther 2009; 8: 2903-13.
167. Tercel M, Atwell GJ, Yang S, et al. Hypoxia-Activated Prodrugs: Substituent Effects on the Properties of Nitro seco-1,2,9,9a- Tetrahydrocyclopropa[c]benz[e]indol-4-one (nitroCBI) Prodrugs of DNA Minor Groove Alkylating Agents. J Med Chem 2009; 52: 7258-72.
168. [Tercel M, Yang S, Atwell GJ, et al. Hypoxic selectivity and solubility-investigating the properties of A-ring substituted nitro seco-1,2,9,9a-tetrahydrocyclopropa[c]benz[e]indol-4-ones (nitroCBIs) as hypoxia-activated prodrugs for antitumor therapy. Bioorg Med Chem 2010; 18: 4997-5006.
169. Milbank JBJ, Stevenson RJ, Ware DC, et al. Synthesis and Evaluation of Stable Bidentate Transition Metal Complexes of 1- (Chloromethyl)-5-hydroxy-3-(5,6,7-trimethoxyindol-2-ylcarbonyl)-2,3-dihydro-1H-pyrrolo[3,2-f]quinoline (seco-6-azaCBI-TMI) as Hypoxia Selective Cytotoxins. J Med Chem 2009; 52: 6822-34.
170. Jin W, Trzupek JD, Rayl TJ, et al. A Unique Class of Duocarmycin and CC-1065 Analogues Subject to Reductive Activation. J Am Chem Soc 2007; 129: 15391-7.
171. Lajiness JP, Robertson WR, Dunwiddie I, et al. O-Amino Phenol Prodrugs Subject to Tunable Reductive Activation. J Med Chem 2010; 53: 7731-8.