Use of pyrrolobenzodiazepines and related covalent-binding DNA-interactive molecules as ADC payloads: Is mechanism related to systemic toxicity?

TY - JOUR

T1 - Use of pyrrolobenzodiazepines and related covalent-binding DNA-interactive molecules as ADC payloads

T2 - Is mechanism related to systemic toxicity?

AU - Jackson, Paul J.M.

AU - Kay, Syafiq

AU - Pysz, Ilona

AU - Thurston, David E.

PY - 2018/12

Y1 - 2018/12

N2 - Antibody-drug conjugates (ADCs) consist of monoclonal antibodies (mAbs) or antibody fragments conjugated to biologically active molecules (usually highly cytotoxic small molecules) through chemical linkers. Although no ADCs containing covalent-binding DNA-interactive payloads have yet been approved (although two containing the DNA-cleaving payload calicheamicin have), of those in clinical trials systemic toxicities are beginning to emerge. This article discusses the observed toxicities in relation to the structures and mechanisms of action of payload type.

AB - Antibody-drug conjugates (ADCs) consist of monoclonal antibodies (mAbs) or antibody fragments conjugated to biologically active molecules (usually highly cytotoxic small molecules) through chemical linkers. Although no ADCs containing covalent-binding DNA-interactive payloads have yet been approved (although two containing the DNA-cleaving payload calicheamicin have), of those in clinical trials systemic toxicities are beginning to emerge. This article discusses the observed toxicities in relation to the structures and mechanisms of action of payload type.

UR - http://www.scopus.com/inward/record.url?scp=85057871725&partnerID=8YFLogxK

U2 - 10.1016/j.ddtec.2018.10.004

DO - 10.1016/j.ddtec.2018.10.004

M3 - Review article

C2 - 30553523

AN - SCOPUS:85057871725

VL - 30

SP - 71

EP - 83

JO - Drug Discovery Today: Technologies

JF - Drug Discovery Today: Technologies

ER -