From Anthramycin to Pyrrolobenzodiazepine (PBD)-Containing Antibody-Drug Conjugates (ADCs).

Autor: Mantaj J; Institute of Pharmaceutical Science, King's College London, Britannia House, 7 Trinity Street, London SE1 1DB, and Femtogenix Ltd, Britannia House, 7 Trinity Street, London, SE1 1DB, UK., Jackson PJ; Institute of Pharmaceutical Science, King's College London, Britannia House, 7 Trinity Street, London SE1 1DB, and Femtogenix Ltd, Britannia House, 7 Trinity Street, London, SE1 1DB, UK., Rahman KM; Institute of Pharmaceutical Science, King's College London, Britannia House, 7 Trinity Street, London SE1 1DB, and Femtogenix Ltd, Britannia House, 7 Trinity Street, London, SE1 1DB, UK., Thurston DE; Professor of Drug Discovery, King's College London, Faculty of Life Sciences & Medicine, Institute of Pharmaceutical Science, Britannia House, 7 Trinity Street, London, SE1 1DB, UK.; Femtogenix Ltd, Britannia House, 7 Trinity Street, London, SE1 1DB, UK.
Jazyk: angličtina
Zdroj: 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.
DOI: 10.1002/anie.201510610
Abstrakt: 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 2 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.
(© 2016 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA.)
Databáze: MEDLINE
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