762245-26-1Relevant articles and documents
Design and Synthesis of Isoquinolidinobenzodiazepine Dimers, a Novel Class of Antibody-Drug Conjugate Payload
Smith, Sean W.,Jammalamadaka, Vasu,Borkin, Dmitry,Zhu, Jianyu,Degrado, Sylvia J.,Lu, Jennifer,Huang, Jianqing,Jiang, Ying-Ping,Jain, Nareshkumar,Junutula, Jagath R.
, p. 56 - 60 (2018)
Antibody-drug conjugates (ADCs) represent an important class of emerging cancer therapeutics. Recent ADC development efforts highlighted the use of pyrrolobenzodiazepine (PBD) dimer payload for the treatment of several cancers. We identified the isoquinolidinobenzodiazepine (IQB) payload (D211), a new class of PBD dimer family of DNA damaging payloads. We have successfully synthesized all three IQB stereoisomers, experimentally showed that the purified (S,S)-D211 isomer is functionally more active than (R,R)-D221 and (S,R)-D231 isomers by >50,000-fold and ~200-fold, respectively. We also synthesized a linker-payload (D212) that uses (S,S)-D211 payload with a cathepsin cleavable linker, a hydrophilic PEG8 spacer, and a thiol reactive maleimide. In addition, homogeneous ADCs generated using D212 linker-payload exhibited ideal physicochemical properties, and anti-CD33 ADC displayed a robust target-specific potency on AML cell lines. These results demonstrate that D212 linker-payload described here can be utilized for developing novel ADC therapeutics for targeted cancer therapy.
POLYCYCLIC AMIDES AS CYTOTOXIC AGENTS
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Page/Page column 233-234, (2020/03/29)
The invention relates to a compound of formula (I): or pharmaceutically acceptable salts, solvates, tautomers, stereoisomers or mixtures thereof; wherein the fused ring moiety is a non-alkylating moiety; and wherein the compounds are useful as medicaments, in particular for use as a drug in an antibody-drug conjugate and in the treatment of a proliferative disease, a bacterial infection, a malarial infection and inflammation.
NOVEL BENZODIAZEPINE DERIVATIVES AND USES THEREOF
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, (2019/12/24)
The present disclosure provides compounds and compositions capable of extending lifespan, and methods of use thereof.