74536-29-1Relevant articles and documents
PYRROLOBENZODIAZEPINE DIMER PRECURSOR AND LIGAND-LINKER CONJUGATE COMPOUND THEREOF
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Paragraph 0251; 0255, (2020/02/18)
The present invention relates to a pyrrolobenzodiazepine dimer prodrug and a ligand-linker conjugate compound thereof, a composition containing these, and therapeutic use thereof particularly as an anticancer drug. The stability of the compounds themselves and the stability thereof in plasma are excellent and the compounds are advantageous in terms of manifestation of toxicity, and thus the compounds are industrially useful in that it is possible to target proliferative diseases such as cancer, to perform a specific treatment, to maximize the drug efficacy, and to minimize the occurrence of side effects.
Utilization of alternate substrates by the first three modules of the epothilone synthetase assembly line
Schneider, Tanya L.,Walsh, Christopher T.,O'Connor, Sarah E.
, p. 11272 - 11273 (2007/10/03)
The epothilones, a family of macrolactone natural products produced by the myxobacterial species Sorangium cellulosum, are of current clinical interest as antitumor agents. Inspection of the structure of the epothilones suggests a hybrid polyketide/nonribosomal peptide biosynthetic origin, and the recent sequencing of the epothilone biosynthetic gene cluster has validated this proposal. Here we have examined unnatural substrates with the first two enzymes of the biosynthetic pathway, EpoA and EpoB, to investigate the enzymatic construction of alternate heterocyclic structures and the subsequent elongation of these products by the third enzyme of the pathway, EpoC. The epothilone biosynthetic machinery can utilize serine to install an oxazole in place of a thiazole in the epothilone structure and will tolerate functionalized donor groups from the EpoA-ACP domain to produce epothilone fragments modified at the C21 position. These studies with the early enzymes of the epothilone biosynthesis cluster suggest that combinatorial biosynthesis may be a viable means for producing a variety of epothilone analogues that incorporate diversity into the heterocycle starter unit. Copyright
Tripeptide aldehyde inhibitors of human rhinovirus 3C protease: Design, synthesis, biological evaluation, and cocrystal structure solution of P1 glutamine isosteric replacements
Webber, Stephen E.,Okano, Koji,Little, Thomas L.,Reich, Siegfried H.,Xin, Yue,Fuhrman, Sheila A.,Matthews, David A.,Love, Robert A.,Hendrickson, Thomas F.,Patick, Amy K.,Meador III, James W.,Ferre, Rose Ann,Brown, Edward L.,Ford, Clifford E.,Binford, Susan L.,Worland, Stephen T.
, p. 2786 - 2805 (2007/10/03)
The investigation of tripeptide aldehydes as reversible covalent inhibitors of human rhinovirus (HRV) 3C protease (3CP) is reported. Molecular models based on the apo crystal structure of HRV-14 3CP and other trypsin- like serine proteases were constructe