Tag: 516.0587

Single-cell proteomic profiling identifies combined AXL and JAK1 inhibition as a novel therapeutic strategy for lung cancer was written by Taverna, Josephine A.;Hung, Chia-Nung;DeArmond, Daniel T.;Chen, Meizhen;Lin, Chun-Lin;Osmulski, Pawel A.;Gaczynska, Maria E.;Wang, Chiou-Miin;Lucio, Nicholas D.;Chou, Chih-Wei;Chen, Chun-Liang;Nazarullah, Alia;Lampkin, Shellye R.;Qiu, Lianqun;Bearss, David J.;Warner, Steven;Whatcott, Clifford J.;Mouritsen, Lars;Wade, Mark;Weitman, Steven;Mesa, Ruben A.;Kirma, Nameer B.;Chao, Wei-Ting;Huang, Tim H.-M.. And the article was included in Cancer Research in 2020.Reference of 1341200-45-0 This article mentions the following:

Cytometry by time-of-flight (CyTOF) simultaneously measures multiple cellular proteins at the single-cell level and is used to assess intertumor and intratumor heterogeneity. Integrative transcriptome analyses were used to investigate how TP-0903, an AXL kinase inhibitor, influences redundant oncogenic pathways in metastatic lung cancer cells. CyTOF profiling revealed that AXL inhibition suppressed SMAD4/TGF尾 signaling and induced JAK1-STAT3 signaling to compensate for the loss of AXL. Interestingly, high JAK1-STAT3 was associated with increased levels of AXL in treatment-naive tumors. Tumors with high AXL, TGF尾, and JAK1 signaling concomitantly displayed CD133-mediated cancer stemness and hybrid epithelial-to-mesenchymal transition features in advanced-stage patients, suggesting greater potential for distant dissemination. Diffusion pseudotime anal. revealed cell-fate trajectories among four different categories that were linked to clinicopathol. features for each patient. Patient-derived organoids (PDO) obtained from tumors with high AXL and JAK1 were sensitive to TP-0903 and ruxolitinib (JAK inhibitor) treatments, supporting the CyTOF findings. This study shows that single-cell proteomic profiling of treatment-naive lung tumors, coupled with ex vivo testing of PDOs, identifies continuous AXL, TGF尾, and JAK1-STAT3 signal activation in select tumors that may be targeted by combined AXL-JAK1 inhibition. 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: 1341200-45-0Reference 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. Simple N-substituted piperazines have been found in many drug molecules. Piperazine and its salts did not induce point mutations in a bacterial test. A series of mutagenicity studies in cells, both in vitro and in vivo, has been completed and showed no evidence of mutagenic effect.Reference of 1341200-45-0

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

TP-0903 inhibits neuroblastoma cell growth and enhances the sensitivity to conventional chemotherapy was written by Aveic, Sanja;Corallo, Diana;Porcu, Elena;Pantile, Marcella;Boso, Daniele;Zanon, Carlo;Viola, Giampietro;Sidarovich, Viktoryia;Mariotto, Elena;Quattrone, Alessandro;Basso, Giuseppe;Tonini, Gian Paolo. And the article was included in European Journal of Pharmacology in 2018.Related Products of 1341200-45-0 This article mentions the following:

Neuroblastoma (NB) is an embryonal tumor with low cure rate for patients classified as high-risk. This class of NB tumors shows a very complex genomic background and requires aggressive treatment strategies. In this work we evaluated the efficacy of the novel multi-kinase inhibitor TP-0903 in impairing NB cells’ growth, proliferation and motility. In vitro studies were performed using cell lines with different mol. background, and in vivo studies were done using the zebrafish exptl. model. Our results confirmed a strong cytotoxicity of TP-0903 already at the sub-micro molar concentrations The observed cytotoxicity of TP-0903 was irreversible and the resulting apoptosis was caspase dependent. In addition, TP-0903 impaired colony formation and neurosphere creation. Depending on the mol. background of the selected NB cell lines, TP-0903 influenced either their capacity to migrate, to complete their cell cycle or both. Likewise, TP-0903 reduced NB cells intravasation in vitro and in vivo. Importantly, TP-0903 showed remarkable pharmacol. efficacy not only as a mono-treatment, but also in combination with conventional chemotherapy drugs (ATRA, cisplatin, and VP16) in different types of NB cells. In conclusion, the multi-kinase activity of TP-0903 allowed the impairment of several biol. processes required for expansion of NB cells, making them more vulnerable to the conventional chemotherapeutics. Altogether, our results support the eligibility of TP-0903 for further (pre)clin. assessments in NB. 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: 1341200-45-0Related Products 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. Piperazine is a fairly basic compound and is an amine solvent. Outside the body, piperazine has a remarkable power to dissolve uric acid and producing a soluble urate, but in clinical experience it has not proved equally successful. Related Products of 1341200-45-0

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

TP-0903 inhibits neuroblastoma cell growth and enhances the sensitivity to conventional chemotherapy was written by Aveic, Sanja;Corallo, Diana;Porcu, Elena;Pantile, Marcella;Boso, Daniele;Zanon, Carlo;Viola, Giampietro;Sidarovich, Viktoryia;Mariotto, Elena;Quattrone, Alessandro;Basso, Giuseppe;Tonini, Gian Paolo. And the article was included in European Journal of Pharmacology in 2018.Related Products of 1341200-45-0 This article mentions the following:

Neuroblastoma (NB) is an embryonal tumor with low cure rate for patients classified as high-risk. This class of NB tumors shows a very complex genomic background and requires aggressive treatment strategies. In this work we evaluated the efficacy of the novel multi-kinase inhibitor TP-0903 in impairing NB cells’ growth, proliferation and motility. In vitro studies were performed using cell lines with different mol. background, and in vivo studies were done using the zebrafish exptl. model. Our results confirmed a strong cytotoxicity of TP-0903 already at the sub-micro molar concentrations The observed cytotoxicity of TP-0903 was irreversible and the resulting apoptosis was caspase dependent. In addition, TP-0903 impaired colony formation and neurosphere creation. Depending on the mol. background of the selected NB cell lines, TP-0903 influenced either their capacity to migrate, to complete their cell cycle or both. Likewise, TP-0903 reduced NB cells intravasation in vitro and in vivo. Importantly, TP-0903 showed remarkable pharmacol. efficacy not only as a mono-treatment, but also in combination with conventional chemotherapy drugs (ATRA, cisplatin, and VP16) in different types of NB cells. In conclusion, the multi-kinase activity of TP-0903 allowed the impairment of several biol. processes required for expansion of NB cells, making them more vulnerable to the conventional chemotherapeutics. Altogether, our results support the eligibility of TP-0903 for further (pre)clin. assessments in NB. 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: 1341200-45-0Related Products 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. Piperazine is a fairly basic compound and is an amine solvent. Outside the body, piperazine has a remarkable power to dissolve uric acid and producing a soluble urate, but in clinical experience it has not proved equally successful. Related Products of 1341200-45-0

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

Single-cell proteomic profiling identifies combined AXL and JAK1 inhibition as a novel therapeutic strategy for lung cancer was written by Taverna, Josephine A.;Hung, Chia-Nung;DeArmond, Daniel T.;Chen, Meizhen;Lin, Chun-Lin;Osmulski, Pawel A.;Gaczynska, Maria E.;Wang, Chiou-Miin;Lucio, Nicholas D.;Chou, Chih-Wei;Chen, Chun-Liang;Nazarullah, Alia;Lampkin, Shellye R.;Qiu, Lianqun;Bearss, David J.;Warner, Steven;Whatcott, Clifford J.;Mouritsen, Lars;Wade, Mark;Weitman, Steven;Mesa, Ruben A.;Kirma, Nameer B.;Chao, Wei-Ting;Huang, Tim H.-M.. And the article was included in Cancer Research in 2020.Reference of 1341200-45-0 This article mentions the following:

Cytometry by time-of-flight (CyTOF) simultaneously measures multiple cellular proteins at the single-cell level and is used to assess intertumor and intratumor heterogeneity. Integrative transcriptome analyses were used to investigate how TP-0903, an AXL kinase inhibitor, influences redundant oncogenic pathways in metastatic lung cancer cells. CyTOF profiling revealed that AXL inhibition suppressed SMAD4/TGFβ signaling and induced JAK1-STAT3 signaling to compensate for the loss of AXL. Interestingly, high JAK1-STAT3 was associated with increased levels of AXL in treatment-naive tumors. Tumors with high AXL, TGFβ, and JAK1 signaling concomitantly displayed CD133-mediated cancer stemness and hybrid epithelial-to-mesenchymal transition features in advanced-stage patients, suggesting greater potential for distant dissemination. Diffusion pseudotime anal. revealed cell-fate trajectories among four different categories that were linked to clinicopathol. features for each patient. Patient-derived organoids (PDO) obtained from tumors with high AXL and JAK1 were sensitive to TP-0903 and ruxolitinib (JAK inhibitor) treatments, supporting the CyTOF findings. This study shows that single-cell proteomic profiling of treatment-naive lung tumors, coupled with ex vivo testing of PDOs, identifies continuous AXL, TGFβ, and JAK1-STAT3 signal activation in select tumors that may be targeted by combined AXL-JAK1 inhibition. 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: 1341200-45-0Reference 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. Simple N-substituted piperazines have been found in many drug molecules. Piperazine and its salts did not induce point mutations in a bacterial test. A series of mutagenicity studies in cells, both in vitro and in vivo, has been completed and showed no evidence of mutagenic effect.Reference of 1341200-45-0

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

TP-0903 inhibits neuroblastoma cell growth and enhances the sensitivity to conventional chemotherapy was written by Aveic, Sanja;Corallo, Diana;Porcu, Elena;Pantile, Marcella;Boso, Daniele;Zanon, Carlo;Viola, Giampietro;Sidarovich, Viktoryia;Mariotto, Elena;Quattrone, Alessandro;Basso, Giuseppe;Tonini, Gian Paolo. And the article was included in European Journal of Pharmacology in 2018.Related Products of 1341200-45-0 This article mentions the following:

Neuroblastoma (NB) is an embryonal tumor with low cure rate for patients classified as high-risk. This class of NB tumors shows a very complex genomic background and requires aggressive treatment strategies. In this work we evaluated the efficacy of the novel multi-kinase inhibitor TP-0903 in impairing NB cells’ growth, proliferation and motility. In vitro studies were performed using cell lines with different mol. background, and in vivo studies were done using the zebrafish exptl. model. Our results confirmed a strong cytotoxicity of TP-0903 already at the sub-micro molar concentrations The observed cytotoxicity of TP-0903 was irreversible and the resulting apoptosis was caspase dependent. In addition, TP-0903 impaired colony formation and neurosphere creation. Depending on the mol. background of the selected NB cell lines, TP-0903 influenced either their capacity to migrate, to complete their cell cycle or both. Likewise, TP-0903 reduced NB cells intravasation in vitro and in vivo. Importantly, TP-0903 showed remarkable pharmacol. efficacy not only as a mono-treatment, but also in combination with conventional chemotherapy drugs (ATRA, cisplatin, and VP16) in different types of NB cells. In conclusion, the multi-kinase activity of TP-0903 allowed the impairment of several biol. processes required for expansion of NB cells, making them more vulnerable to the conventional chemotherapeutics. Altogether, our results support the eligibility of TP-0903 for further (pre)clin. assessments in NB. 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: 1341200-45-0Related Products 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. Piperazine is a fairly basic compound and is an amine solvent. Outside the body, piperazine has a remarkable power to dissolve uric acid and producing a soluble urate, but in clinical experience it has not proved equally successful. Related Products of 1341200-45-0

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