Systematic identification of biomarker-driven drug combinations to overcome resistance was written by Rees, Matthew G.;Brenan, Lisa;do Carmo, Mariana;Duggan, Patrick;Bajrami, Besnik;Arciprete, Michael;Boghossian, Andrew;Vaimberg, Emma;Ferrara, Steven J.;Lewis, Timothy A.;Rosenberg, Danny;Sangpo, Tenzin;Roth, Jennifer A.;Kaushik, Virendar K.;Piccioni, Federica;Doench, John G.;Root, David E.;Johannessen, Cory M.. And the article was included in Nature Chemical Biology in 2022.Electric Literature of C24H27N5O2 The following contents are mentioned in the article:
The ability to understand and predict variable responses to therapeutic agents may improve outcomes in patients with cancer. We hypothesized that the basal gene-transcription state of cancer cell lines, coupled with cell viability profiles of small mols., might be leveraged to nominate specific mechanisms of intrinsic resistance and to predict drug combinations that overcome resistance. We analyzed 564,424 sensitivity profiles to identify candidate gene-compound pairs, and validated nine such relationships. We determined the mechanism of a novel relationship, in which expression of the serine hydrolase enzymes monoacylglycerol lipase (MGLL) or carboxylesterase 1 (CES1) confers resistance to the histone lysine demethylase inhibitor GSK-J4 by direct enzymic modification. Insensitive cell lines could be sensitized to GSK-J4 by inhibition or gene knockout. These anal. and mechanistic studies highlight the potential of integrating gene-expression features with small-mol. response to identify patient populations that are likely to benefit from treatment, to nominate rational candidates for combinations and to provide insights into mechanisms of action. This study involved multiple reactions and reactants, such as Ethyl 3-((6-(4,5-dihydro-1H-benzo[d]azepin-3(2H)-yl)-2-(pyridin-2-yl)pyrimidin-4-yl)amino)propanoate (cas: 1373423-53-0Electric Literature of C24H27N5O2).
Ethyl 3-((6-(4,5-dihydro-1H-benzo[d]azepin-3(2H)-yl)-2-(pyridin-2-yl)pyrimidin-4-yl)amino)propanoate (cas: 1373423-53-0) belongs to pyrimidine derivatives. The pyrimidine ring system has wide occurrence in nature as substituted and ring fused compounds and derivatives. Drugs having the pyrimidine motif have manifested to exhibit gratifying biological activity like anticancer, antiviral, anti-inflammatory, antibacterial, and antihypertensive activities.Electric Literature of C24H27N5O2
Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia