TP-0903 is active in models of drug-resistant acute myeloid leukemia. was written by Jeon, Jae Yoon;Buelow, Daelynn R;Garrison, Dominique A;Niu, Mingshan;Eisenmann, Eric D;Huang, Kevin M;Zavorka Thomas, Megan E;Weber, Robert H;Whatcott, Clifford J;Warner, Steve L;Orwick, Shelley J;Carmichael, Bridget;Stahl, Emily;Brinton, Lindsey T;Lapalombella, Rosa;Blachly, James S;Hertlein, Erin;Byrd, John C;Bhatnagar, Bhavana;Baker, Sharyn D. And the article was included in JCI insight in 2020.Application of 1341200-45-0 This article mentions the following:
Effective treatment for AML is challenging due to the presence of clonal heterogeneity and the evolution of polyclonal drug resistance. Here, we report that TP-0903 has potent activity against protein kinases related to STAT, AKT, and ERK signaling, as well as cell cycle regulators in biochemical and cellular assays. In vitro and in vivo, TP-0903 was active in multiple models of drug-resistant FLT3 mutant AML, including those involving the F691L gatekeeper mutation and bone marrow microenvironment-mediated factors. Furthermore, TP-0903 demonstrated preclinical activity in AML models with FLT3-ITD and common co-occurring mutations in IDH2 and NRAS genes. We also showed that TP-0903 had ex vivo activity in primary AML cells with recurrent mutations including MLL-PTD, ASXL1, SRSF2, and WT1, which are associated with poor prognosis or promote clinical resistance to AML-directed therapies. Our preclinical studies demonstrate that TP-0903 is a multikinase inhibitor with potent activity against multiple drug-resistant models of AML that will have an immediate clinical impact in a heterogeneous disease like AML. In the experiment, the researchers used many compounds, for example, 2-((5-Chloro-2-((4-((4-methylpiperazin-1-yl)methyl)phenyl)amino)pyrimidin-4-yl)amino)-N,N-dimethylbenzenesulfonamide (cas: 1341200-45-0Application of 1341200-45-0).
2-((5-Chloro-2-((4-((4-methylpiperazin-1-yl)methyl)phenyl)amino)pyrimidin-4-yl)amino)-N,N-dimethylbenzenesulfonamide (cas: 1341200-45-0) belongs to piperazine derivatives. A form in which piperazine is commonly available industrially is as the hexahydrate, C4H10N2. 6H2O, which melts at 44 °C and boils at 125–130 °C. Although many piperazine derivatives occur naturally, piperazine itself can be synthesized by reacting alcoholic ammonia with 1,2-dichloroethane, by the action of sodium and ethylene glycol on ethylene diamine hydrochloride, or by reduction of pyrazine with sodium in ethanol.Application of 1341200-45-0
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Piperazine – Wikipedia,
Piperazines – an overview | ScienceDirect Topics