61032-41-5Relevant academic research and scientific papers
VISUAL DETECTION OF PBD INDUCED DNA CROSSLINKS
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, (2021/04/23)
The present invention relates to the field of oncology, laboratory tools and methods, and especially anti-tumor DNA crosslinking agents. Most patients with advanced solid tumors develop resistance to chemotherapy due to the ability of cancer cells to repair or tolerate sustained DNA damages. The inventors showed that the compounds according to the present invention allow the detection and visualization of alkylated DNA damages induced by PBDs without altering their DNA crosslinking ability. This enables the study of the effect and properties of PBDs. In particular, the present invention relates new derivates of PBD molecules and their synthesis. The present invention also relates to a method for visualizing DNA crosslinking; to a method for assessing the resistance of a tumor to a crosslinking agent and to a method for identifying a molecule or treatment for improving the efficiency of a crosslinking agent.
COMPOSITIONS AND METHODS RELATED TO MOLECULAR CONJUGATION
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Page/Page column 80; 81, (2021/06/11)
The invention relates to activated Michael acceptor (AMA) compounds that can undergo conjugation with biomolecules containing Michael donor moieties, thereby providing plasma-stable antibody-drug conjugates (ADCs). Pharmaceutical compositions of the ADCs are disclosed as well. Also provided herein are a number of applications (e.g., therapeutic applications) in which the compositions are useful.
Structure–activity relationship study of novel quinazoline-based 1,6-naphthyridinones as MET inhibitors with potent antitumor efficacy
Zhuo, Lin-Sheng,Wu, Feng-Xu,Wang, Ming-Shu,Xu, Hong-Chuang,Yang, Fan-Peng,Tian, Yan-Guang,Zhao, Xing-E.,Ming, Zhi-Hui,Zhu, Xiao-Lei,Hao, Ge-Fei,Huang, Wei
, (2020/09/09)
As a privileged scaffold, the quinazoline ring is widely used in the development of EGFR inhibitors, while few quinazoline-based MET inhibitors are reported. In our ongoing efforts to develop new MET-targeted anticancer drug candidates, a series of quinaz
FUSED HETEROCYCLIC BENZODIAZEPINE DERIVATIVES AND USES THEREOF
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Page/Page column 85-86, (2020/05/29)
The present disclosure provides compounds and compositions capable of extending lifespan, and methods of use thereof.
NOVEL BENZODIAZEPINE DERIVATIVES AND USES THEREOF
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Paragraph 0508-0510, (2019/12/24)
The present disclosure provides compounds and compositions capable of extending lifespan, and methods of use thereof.
METHODS OF PREPARING INDOLINOBENZODIAZEPINE DERIVATIVES
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, (2018/11/22)
The invention provides novel methods for preparing indolinobenzodiazepine monomer compounds and their synthetic precursors.
ISOQUINOLIDINOBENZODIAZEPINES
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Paragraph 000469-000471, (2018/04/13)
This disclosure provides novel isoquinolidinobenzodiazepines. These compounds can also be incorporated into antibody-drug conjugates.
ISOQUINOLIDINOBENZODIAZEPINE (IQB)-1(CHLOROMETHYL)-2,3-DIHYDRO-1H-BENZO[E]INDOLE (CBI) DIMERS
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Paragraph 0009; 00114-00118, (2018/04/27)
Provided herein are isoquinolidinobenzodiazepine (IQB)-1(chloromethyl)-2,3-dihydro-1H-benzo[e]indole (CBI) dimers, antibody-drug conjugates comprising them and methods of use for killing cells and treating disease.
Histone lysine methyltransferase structure activity relationships that allow for segregation of G9a inhibition and anti-Plasmodium activity
Sundriyal, Sandeep,Chen, Patty B.,Lubin, Alexandra S.,Lueg, Gregor A.,Li, Fengling,White, Andrew J. P.,Malmquist, Nicholas A.,Vedadi, Masoud,Scherf, Artur,Fuchter, Matthew J.
, p. 1069 - 1092 (2017/07/12)
Plasmodium falciparum HKMTs (PfHKMTs) play a key role in controlling Plasmodium gene expression and represent exciting new anti-malarial epigenetic targets. Using an inhibitor series derived from the diaminoquinazoline HKMT inhibitory chemotype, we have previously identified compounds with highly promising antimalarial activity, including irreversible asexual cycle blood stage-independent cytotoxic activity at nM concentrations, oral efficacy in in vivo models of disease, and the unprecedented ability to reactivate dormant liver stage parasites (hypnozoites). However, future development of this series will need to address host versus parasite selectivity, where inhibitory activity against human G9a is removed from the lead compounds, while maintaining potent anti-Plasmodium activity. Herein, we report an extensive study of the SAR of this series against both G9a and P. falciparum. We have identified key SAR features which demonstrate that high parasite vs. G9a selectivity can be achieved by selecting appropriate substituents at position 2, 4 and 7 of the quinazoline ring. We have also, in turn, discovered that potent G9a inhibitors can be identified by employing a 6-carbon 'Nle mimic' at position 7. Together, this data suggests that while broadly similar, the G9a and potential PfHKMT target(s) binding pockets and/or binding modes of the diaminoquinazoline analogues exhibit clear and exploitable differences. Based on this, we believe this scaffold to have clear potential for development into a novel anti-malarial therapeutic.
PYRROLOBENZODIAZEPINE ANTIBODY DRUG CONJUGATES AND METHODS OF USE
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, (2017/04/23)
The invention provides antibody-drug conjugates comprising an antibody conjugated to a pyrrolobenzodiazepine drug moiety via a disulfide linker, pyrrolobenzodiazepine linker-drug intermediates, and methods of using the antibody-drug conjugates.
