2488-22-4Relevant articles and documents
Effect of Linker Stereochemistry on the Activity of Indolinobenzodiazepine Containing Antibody-Drug Conjugates (ADCs)
Reid, Emily E.,Archer, Katie E.,Shizuka, Manami,Wilhelm, Alan,Yoder, Nicholas C.,Bai, Chen,Fishkin, Nathan E.,Harris, Luke,Maloney, Erin K.,Salomon, Paulin,Hong, Erica,Wu, Rui,Ab, Olga,Jin, Shan,Lai, Katharine C.,Sikka, Surina,Chari, Ravi V. J.,Miller, Michael L.
, p. 1193 - 1197 (2019)
Antibody-drug conjugates (ADCs) that incorporate potent indolinobenzodiazepine DNA alkylators as the payload component are currently undergoing clinical evaluation. In one ADC design, the payload molecules are linked to the antibody through a peptidase-labile l-Ala-l-Ala linker. In order to determine the role of amino acid stereochemistry on antitumor activity and tolerability, we incorporated l- and d-alanyl groups in the dipeptide, synthesized all four diastereomers, and prepared and tested the corresponding ADCs. Results of our preclinical evaluation showed that the l-Ala-l-Ala configuration provided the ADC with the highest therapeutic index (antitumor activity vs toxicity).
CYTOTOXIC BIS-BENZODIAZEPINE DERIVATIVES AND CONJUGATES THEREOF WITH CELL-BINDING AGENTS FOR INHIBITING ABNORMAL CELL GROWTH OR FOR TREATING PROLIFERATIVE DISEASES
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Paragraph 00289, (2020/10/20)
The invention relates to benzodiazepine derivatives with antiproliferative activity and more specifically to benzodiazepine compounds of formulae (I), (II), (TI) and (T2). The invention also provides conjugates of the benzodiazepine compounds linked to a
CYTOTOXIC BENZODIAZEPINE DERIVATIVES AND CONJUGATES THEREOF
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Page/Page column 124;, (2018/11/22)
The invention relates to novel benzodiazepine derivatives with antiproliferative activity and more specifically to novel benzodiazepine compounds of formulae (I) and (II). The invention also provides conjugates of the benzodiazepine compounds linked to a
