Tag: 516.0587

Autophagy inhibition improves the cytotoxic effects of receptor tyrosine kinase inhibitors was written by Aveic, Sanja;Pantile, Marcella;Polo, Pierfrancesco;Sidarovich, Viktoryia;De Mariano, Marilena;Quattrone, Alessandro;Longo, Luca;Tonini, Gian Paolo. And the article was included in Cancer Cell International in 2018.Application of 1341200-45-0 This article mentions the following:

Autophagy activation is among the possible obstacles for good efficacy of the therapy with RTKi. Under different treatment conditions we measured autophagic flux using immunoblot and immunofluorescence assays. Death induction was validated by trypan blue exclusion assay and FACS anal. (calcein-AM/propidium iodide). The NB cell lines SH-SY5Y and Kelly were used for the in vitro study. In order to define whether autophagy might be a limiting factor for the efficacy of RTKi in NB cells, we firstly checked its activation following the treatment with several RTKi. Next, we investigated the possibility to increase their therapeutic efficiency by combining RTKi with autophagy blocking agents in vitro. We exploited the effectiveness of three RTKi either alone or in combination with autophagy inhibitors (Chloroquine-CQ and Spautin-1). We demonstrated that autophagy induction was drug-dependent, and that its inhibition increased the anti-tumor activity of a single RTKi unevenly. We observed that the combined use of blocking agents which impair late autophagy events, such as CQ, and RTKi can be more effective with respect to the use of RTKi alone. In the present report, we assessed the conditions under which autophagy is activated during the use of different RTKi currently in the pre-clin. evaluation for NB. We summarized the achievements of combined RTK/autophagy inhibitors treatment as a promising approach to enhance the efficacy of RTKi in impairing tumor cells viability. 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. The piperazine scaffold is often found in biologically active compounds in different therapeutic areas. These therapeutic areas include antifungals, antidepressants, antivirals, and serotonin receptor (5-HT) antagonists/agonists. Piperazines are very broad chemical group, covering a wide range of drugs from antidepressants to antihistamines. The connecting property of all these chemicals is the presence of a piperazine functional group.Application of 1341200-45-0

Referemce:
Piperazine – Wikipedia,
Piperazines – an overview | ScienceDirect Topics

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

Referemce:
Piperazine – Wikipedia,
Piperazines – an overview | ScienceDirect Topics