161948-58-9Relevant academic research and scientific papers
Rad51/BRCA2 disruptors inhibit homologous recombination and synergize with olaparib in pancreatic cancer cells
Roberti, Marinella,Schipani, Fabrizio,Bagnolini, Greta,Milano, Domenico,Giacomini, Elisa,Falchi, Federico,Balboni, Andrea,Manerba, Marcella,Farabegoli, Fulvia,De Franco, Francesca,Robertson, Janet,Minucci, Saverio,Pallavicini, Isabella,Di Stefano, Giuseppina,Girotto, Stefania,Pellicciari, Roberto,Cavalli, Andrea
, p. 80 - 92 (2019)
Olaparib is a PARP inhibitor (PARPi). For patients bearing BRCA1 or BRCA2 mutations, olaparib is approved to treat ovarian cancer and in clinical trials to treat breast and pancreatic cancers. In BRCA2-defective patients, PARPi inhibits DNA single-strand break repair, while BRCA2 mutations hamper double-strand break repair. Recently, we identified a series of triazole derivatives that mimic BRCA2 mutations by disrupting the Rad51-BRCA2 interaction and thus double-strand break repair. Here, we have computationally designed, synthesized, and tested over 40 novel derivatives. Additionally, we designed and conducted novel biological assays to characterize how they disrupt the Rad51-BRCA2 interaction and inhibit double-strand break repair. These compounds synergized with olaparib to target pancreatic cancer cells with functional BRCA2. This supports the idea that small organic molecules can mimic genetic mutations to improve the profile of anticancer drugs for precision medicine. Moreover, this paradigm could be exploited in other genetic pathways to discover innovative anticancer targets and drug candidates.
Substituted Benzo-Pyrido-Triazolo-Diazepine Compounds
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Page/Page column 99-100, (2011/10/13)
The present invention relates to substituted benzo-pyrido-triazolo-diazepine compounds and methods of synthesizing these compounds. The present invention also relates to pharmaceutical compositions containing substituted benzo-pyrido-triazolo-diazepine compounds and methods of treating cell proliferative disorders, such as cancer, by administering these compounds or pharmaceutical compositions to subjects in need thereof.
Certain diacyl hydrazine derivatives
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, (2008/06/13)
The invention concerns acid derivatives of formula I and pharmaceutically acceptable metabolically labile esters or amides thereof, and pharmaceutically acceptable salts thereof, in which R1, R2, R3, X1, Q, X2 and G have the meanings given in the specification. The invention also concerns processes for the preparation of the acid derivatives of formula I, pharmaceutical compositions containing them and their use as inhibitors of the binding of fibrinogen to glycoprotein IIb/IIIa.
