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From Anthramycin to Pyrrolobenzodiazepine (PBD)-Containing Antibody-Drug Conjugates (ADCs).
- Source :
-
Angewandte Chemie (International ed. in English) [Angew Chem Int Ed Engl] 2017 Jan 09; Vol. 56 (2), pp. 462-488. Date of Electronic Publication: 2016 Nov 15. - Publication Year :
- 2017
-
Abstract
- The pyrrolo[2,1-c][1,4]benzodiazepines (PBDs) are a family of sequence-selective DNA minor-groove binding agents that form a covalent aminal bond between their C11-position and the C2-NH <subscript>2</subscript> groups of guanine bases. The first example of a PBD monomer, the natural product anthramycin, was discovered in the 1960s, and the best known PBD dimer, SJG-136 (also known as SG2000, NSC 694501 or BN2629), was synthesized in the 1990s and has recently completed Phase II clinical trials in patients with leukaemia and ovarian cancer. More recently, PBD dimer analogues are being attached to tumor-targeting antibodies to create antibody-drug conjugates (ADCs), a number of which are now in clinical trials, with many others in pre-clinical development. This Review maps the development from anthramycin to the first PBD dimers, and then to PBD-containing ADCs, and explores both structure-activity relationships (SARs) and the biology of PBDs, and the strategies for their use as payloads for ADCs.<br /> (© 2016 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA.)
- Subjects :
- Anthramycin chemical synthesis
Anthramycin chemistry
Antibiotics, Antineoplastic chemical synthesis
Antibiotics, Antineoplastic chemistry
Antibodies chemistry
Benzodiazepines chemical synthesis
Benzodiazepines chemistry
Cell Proliferation drug effects
Female
Humans
Leukemia pathology
Molecular Structure
Ovarian Neoplasms pathology
Pyrroles chemical synthesis
Pyrroles chemistry
Anthramycin pharmacology
Antibiotics, Antineoplastic pharmacology
Antibodies pharmacology
Benzodiazepines pharmacology
Leukemia drug therapy
Ovarian Neoplasms drug therapy
Pyrroles pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 1521-3773
- Volume :
- 56
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Angewandte Chemie (International ed. in English)
- Publication Type :
- Academic Journal
- Accession number :
- 27862776
- Full Text :
- https://doi.org/10.1002/anie.201510610