Discovery of novel drug sensitivities in T-PLL by high-throughput ex vivo drug testing and mutation profiling was written by Andersson, E. I.;Putzer, S.;Yadav, B.;Dufva, O.;Khan, S.;He, L.;Sellner, L.;Schrader, A.;Crispatzu, G.;Oles, M.;Zhang, H.;Adnan-Awad, S.;Lagstrom, S.;Bellanger, D.;Mpindi, J. P.;Eldfors, S.;Pemovska, T.;Pietarinen, P.;Lauhio, A.;Tomska, K.;Cuesta-Mateos, C.;Faber, E.;Koschmieder, S.;Brummendorf, T. H.;Kytola, S.;Savolainen, E.-R.;Siitonen, T.;Ellonen, P.;Kallioniemi, O.;Wennerberg, K.;Ding, W.;Stern, M.-H.;Huber, W.;Anders, S.;Tang, J.;Aittokallio, T.;Zenz, T.;Herling, M.;Mustjoki, S.. And the article was included in Leukemia in 2018.Electric Literature of C24H27N5O2 The following contents are mentioned in the article:
T-cell prolymphocytic leukemia (T-PLL) is a rare and aggressive neoplasm of mature T-cells with an urgent need for rationally designed therapies to address its notoriously chemo-refractory behavior. The median survival of T-PLL patients is <2 years and clin. trials are difficult to execute. Here we systematically explored the diversity of drug responses in T-PLL patient samples using an ex vivo drug sensitivity and resistance testing platform and correlated the findings with somatic mutations and gene expression profiles. Intriguingly, all T-PLL samples were sensitive to the cyclin-dependent kinase inhibitor SNS-032, which overcame stromal-cell-mediated protection and elicited robust p53-activation and apoptosis. Across all patients, the most effective classes of compounds were histone deacetylase, phosphoinositide-3 kinase/AKT/mammalian target of rapamycin, heat-shock protein 90 and BH3-family protein inhibitors as well as p53 activators, indicating previously unexplored, novel targeted approaches for treating T-PLL. Although Janus-activated kinase-signal transducer and activator of transcription factor (JAK-STAT) pathway mutations were common in T-PLL (71% of patients), JAK-STAT inhibitor responses were not directly linked to those or other T-PLL-specific lesions. Overall, we found that genetic markers do not readily translate into novel effective therapeutic vulnerabilities. In conclusion, novel classes of compounds with high efficacy in T-PLL were discovered with the comprehensive ex vivo drug screening platform warranting further studies of synergisms and clin. testing. 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. Pyrimidines are isomeric with two other forms of diazines: pyridazine, with the nitrogen atoms in the 1 and 2 positions; and pyrazine, with the nitrogen atoms in the 1 and 4 positions. A Cu-catalyzed and 4-HO-TEMPO-mediated [3 + 3] annulation of commercially available amidines with saturated ketones enables an efficient and facile synthesis of structurally important pyrimidines via a cascade reaction of oxidative dehydrogenation/annulation/oxidative aromatization.Electric Literature of C24H27N5O2
Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia