Tag: 500-600

Iriyama, Noriyoshi; Miura, Katsuhiro; Uchino, Yoshihito; Takahashi, Hiromichi; Nakagawa, Masaru; Iizuka, Kazuhide; Hamada, Takashi; Koike, Takashi; Kurihara, Kazuya; Nakayama, Tomohiro; Takei, Masami; Hatta, Yoshihiro; Nakamura, Hideki published an article in 2022, the title of the article was Relationship between Carnitine Deficiency and Tyrosine Kinase Inhibitor Use in Patients with Chronic Myeloid Leukemia.HPLC of Formula: 380843-75-4 And the article contains the following content:

Some chemotherapeutic agents cause carnitine deficiency, which causes general fatigue. However, there is no study on carnitine deficiency in patients with chronic myeloid leukemia (CML) during tyrosine kinase inhibitor (TKI) therapy. In this study, we investigated carnitine concentrations in patients with CML receiving TKI therapy. This study included patients with well-controlled CML. Total carnitine and free carnitine concentrations were evaluated using the enzyme cycling method. The brief fatigue inventory (BFI) and cancer fatigue scale (CFS) were used to assess general fatigue developed during TKI therapy. Fifty-five patients on TKI therapy were included. Of these, 12 (21.8%) patients had low free carnitine concentrations Free carnitine concentrations were higher in men than in women. Younger age was closely associated with lower free carnitine concentrations TKI type, TKI dose, treatment response, or therapy duration were not associated with free carnitine concentrations None of the scores (the global fatigue score with the BFI and CFS score) correlated with carnitine concentrations Concentrations of free carnitine in patients in the treatment-free remission group were slightly higher than those in the TKI group, with only 9.1% having a low concentration of free carnitine. Carnitine deficiency is probably not a major cause of general fatigue but may occur in patients with CML receiving TKI therapy. The experimental process involved the reaction of 4-((2,4-Dichloro-5-methoxyphenyl)amino)-6-methoxy-7-(3-(4-methylpiperazin-1-yl)propoxy)quinoline-3-carbonitrile(cas: 380843-75-4).HPLC of Formula: 380843-75-4

The Article related to carnitine tyrosine kinase inhibitor anticancer chronic myeloid leukemia, carnitine deficiency, chronic myeloid leukemia, general fatigue, tyrosine kinase inhibitor, Mammalian Pathological Biochemistry: Oncology and other aspects.HPLC of Formula: 380843-75-4

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

On February 1, 2022, Campbell, Marcia R.; Ruiz-Saenz, Ana; Peterson, Elliott; Agnew, Christopher; Ayaz, Pelin; Garfinkle, Sam; Littlefield, Peter; Steri, Veronica; Oeffinger, Julie; Sampang, Maryjo; Shan, Yibing; Shaw, David E.; Jura, Natalia; Moasser, Mark M. published an article.SDS of cas: 380843-75-4 The title of the article was Targetable HER3 functions driving tumorigenic signaling in HER2-amplified cancers. And the article contained the following:

Effective inactivation of the HER2-HER3 tumor driver has remained elusive because of the challenging attributes of the pseudokinase HER3. We report a structure-function study of constitutive HER2-HER3 signaling to identify opportunities for targeting. The allosteric activation of the HER2 kinase domain (KD) by the HER3 KD is required for tumorigenic signaling and can potentially be targeted by allosteric inhibitors. ATP binding within the catalytically inactive HER3 KD provides structural rigidity that is important for signaling, but this is mimicked, not opposed, by small mol. ATP analogs, reported here in a bosutinib-bound crystal structure. Mutational disruption of ATP binding and mol. dynamics simulation of the apo KD of HER3 identify a conformational coupling of the ATP pocket with a hydrophobic AP-2 pocket, analogus to EGFR, that is critical for tumorigenic signaling and feasible for targeting. The value of these potential target sites is confirmed in tumor growth assays using gene replacement techniques. The experimental process involved the reaction of 4-((2,4-Dichloro-5-methoxyphenyl)amino)-6-methoxy-7-(3-(4-methylpiperazin-1-yl)propoxy)quinoline-3-carbonitrile(cas: 380843-75-4).SDS of cas: 380843-75-4

The Article related to amplified cancer epidermal growth factor receptor tumorigenic signaling, ap-2 pocket, erbb2, erbb3, her2, her3, allosteric inhibitor, bosutinib, breast cancer, Mammalian Pathological Biochemistry: Oncology and other aspects.SDS of cas: 380843-75-4

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

Huang, Jing; Huo, Hongqi; Lu, Rong published an article in 2022, the title of the article was A novel signature of necroptosis-associated genes as a potential prognostic tool for head and neck squamous cell carcinoma.Electric Literature of 380843-75-4 And the article contains the following content:

Head and neck squamous cell carcinoma (HNSCC) arises from squamous cells in the oral cavity, pharynx and larynx. Although HNSCC is sensitive to radiotherapy, patient prognosis is poor. Necroptosis is a novel programmed form of necrotic cell death. The prognostic value of necroptosis-associated gene expression in HNSCC has not been explored. We downloaded mRNA expression data of HNSCC patients from TCGA databases and Gene Expression Omnibus (GEO) databases, and compared gene expression between tumor tissues and adjacent normal tissues to identify differentially expressed genes (DEGs) and necroptosis-related prognostic genes. A model with necroptosis-related genes was established to predict patient prognosis via LASSO method and Kaplan-Meier anal. GSE65858 data set (n = 270) from GEO was used to verify the model’s predictive ability. Gene set enrichment analyses, immune microenvironment anal., principal component anal., and anti-tumor compound IC50 prediction were also performed. We identified 49 DEGs and found 10 DEGs were associated with patient survival (p < 0.05). A risk model of 6-gene signature was constructed using the TCGA training data set and further validated with the GEO data set. Patients in the low-risk group survived longer than those in the high-risk group (p < 0.05) in the GEO validation sets. Functional anal. showed the two patient groups were associated with distinct immunity conditions and IC50. We constructed a prognostic model with 6 necroptosis-associated genes for HNSCC. The model has potential usage to guide treatment because survival was different between the two groups. The experimental process involved the reaction of 4-((2,4-Dichloro-5-methoxyphenyl)amino)-6-methoxy-7-(3-(4-methylpiperazin-1-yl)propoxy)quinoline-3-carbonitrile(cas: 380843-75-4).Electric Literature of 380843-75-4

The Article related to head and neck squamous cell carcinoma necroptosis prognosis, immune, necroptosis, prognosis, risk score, squamous cell carcinoma, tumor, Mammalian Pathological Biochemistry: Oncology and other aspects.Electric Literature of 380843-75-4

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

Bankar, Aniket; Lipton, Jeffrey H. published an article in 2022, the title of the article was Association of creatine kinase elevation with clinical outcomes in chronic myeloid leukemia: a retrospective cohort study.SDS of cas: 380843-75-4 And the article contains the following content:

Implications of creatine kinase (CK) elevation, a frequent complication of tyrosine kinase inhibitor (TKI) treatment for chronic myeloid leukemia (CML), on its key treatment outcomes (overall survival (OS) and event-free survival (EFS)), remain unknown. In this single center, retrospective study on 283 chronic phase CML patients on first-line TKI (median follow-up of 8.8 years), 71.7% patients had hyperCKemia with no difference in incidence between imatinib and second generation TKIs (SG-TKIs). In multivariable Cox regression anal., hyperCKemia was associated with better OS and intermediate- and high-Sokal risk score with worse OS. In multivariable Cox regression for EFS, hyperCKemia and treatment with SG-TKI were associated with improved EFS while intermediate or high Sokal index and higher comorbidities showed worse EFS. Our study provides an evidence on the prognostic value of hyperCKemia in CML and informs clinicians not to change TKI based solely on laboratory elevations of CK. The experimental process involved the reaction of 4-((2,4-Dichloro-5-methoxyphenyl)amino)-6-methoxy-7-(3-(4-methylpiperazin-1-yl)propoxy)quinoline-3-carbonitrile(cas: 380843-75-4).SDS of cas: 380843-75-4

The Article related to creatine kinase chronic myeloid leukemia, chronic myeloid leukemia, creatine kinase, tyrosine kinase inhibitors, Mammalian Pathological Biochemistry: Oncology and other aspects.SDS of cas: 380843-75-4

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

On November 30, 2021, Patrick, Shruti; Gowda, Pruthvi; Lathoria, Kirti; Suri, Vaishali; Sen, Ellora published an article.HPLC of Formula: 380843-75-4 The title of the article was YAP1-mediated regulation of mitochondrial dynamics in IDH1 mutant gliomas. And the article contained the following:

Mutation of the isocitrate dehydrogenase 1 (IDH1) gene leads to the production of oncometabolite D-2-hydroxyglutarate (2-HG) from α-ketoglutarate and is associated with better prognosis in glioma. As Yes-associated protein 1 (YAP1) is an important regulator of tumor progression, its role in glioma expressing IDH1 with an R132H mutation was investigated. Diminished nuclear levels of YAP1 in IDH1 mutant glioma tissues and cell lines were accompanied by decreased levels of mitochondrial transcription factor A (TFAM). Luciferase reporter assays and chromatin immunoprecipitation were used to investigate the functionality of the TEAD2-binding site on the TFAM promoter in mediating its YAP1-dependent expression. YAP1- dependent mitochondrial fragmentation and ROS generation were accompanied by decreased telomerase reverse transcriptase (TERT) levels and increased mitochondrial TERT localization in IDH1 R132H cells. Treatment with the Src kinase inhibitor bosutinib, which prevents extranuclear shuttling of TERT, further elevated ROS in IDH1 R132H cells and triggered apoptosis. Importantly, bosutinib treatment also increased ROS levels and induced apoptosis in IDH1 wild-type cells when YAP1 was concurrently depleted. These findings highlight the involvement of YAP1 in coupling mitochondrial dysfunction with mitochondrial shuttling of TERT to constitute an essential non-canonical function of YAP1 in the regulation of redox homeostasis. The experimental process involved the reaction of 4-((2,4-Dichloro-5-methoxyphenyl)amino)-6-methoxy-7-(3-(4-methylpiperazin-1-yl)propoxy)quinoline-3-carbonitrile(cas: 380843-75-4).HPLC of Formula: 380843-75-4

The Article related to yap mitochondrial dynamic idh mutant glioma, glioma, idh1, mitochondria, tert, tfam, yap1, Mammalian Pathological Biochemistry: Oncology and other aspects.HPLC of Formula: 380843-75-4

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

Fan, Mengtian; Wu, Jinghong; Li, Xian; Jiang, Yingjiu; Wang, Xiaowen; Bie, Mengjun; Weng, Yaguang; Chen, Sicheng; Chen, Bin; An, Liqin; Zhang, Menghao; Huang, Gaigai; Zhu, Mengying; Shi, Qiong published an article in 2021, the title of the article was CX3CL1 promotes tumour cell by inducing tyrosine phosphorylation of cortactin in lung cancer.SDS of cas: 380843-75-4 And the article contains the following content:

It has been reported that chemokine CX3CL1 can regulate various tumors by binding to its unique receptor CX3CR1. However, the effect of CX3CL1-CX3CR1 on the lung adenocarcinoma and lung squamous cell carcinoma is still unclear. Here, we showed that CX3CL1 can further invasion and migration of lung adenocarcinoma A549 and lung squamous cell carcinoma H520. In addition, Western blot and immunofluorescence test indicated CX3CL1 up-regulated the phosphorylation level of cortactin, which is a marker of cell pseudopodium. Meanwhile, the phosphorylation levels of c-Src and c-Abl, which are closely related to the regulation of cortactin phosphorylation, are elevated. Nevertheless, the src/abl inhibitor bosutinib and mutations of cortactin phosphorylation site could inhibit the promotion effect of CX3CL1 on invasion and migration of A549 and H520. Moreover, these results of MTT, Hoechst staining and Western blot suggested that CX3CL1 had no effect on the proliferation and apoptosis of A549 and H520 in vitro. The effects of CX3CL1 were also verified by the s.c. tumor formation in nude mice, which showed that it could promote proliferation and invasion of A549 in vivo. In summary, our results indicated that CX3CL1 furthered invasion and migration in lung cancer cells partly via activating cortactin, and CX3CL1 may be a potential mol. in regulating the migration and invasion of lung cancer. The experimental process involved the reaction of 4-((2,4-Dichloro-5-methoxyphenyl)amino)-6-methoxy-7-(3-(4-methylpiperazin-1-yl)propoxy)quinoline-3-carbonitrile(cas: 380843-75-4).SDS of cas: 380843-75-4

The Article related to lung cancer cx3cl1 tyrosine phosphorylation, cx3cl1, cancer, cortactin, invasion, lung, Mammalian Pathological Biochemistry: Oncology and other aspects.SDS of cas: 380843-75-4

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

Janssen, Lando; Blijlevens, Nicole M. A.; Drissen, Meggie M. C. M.; Bakker, Esmee A.; Nuijten, Malou A. H.; Janssen, Jeroen J. W. M.; Timmers, Silvie; Hopman, Maria T. E. published an article in 2021, the title of the article was Fatigue in chronic myeloid leukemia patients on tyrosine kinase inhibitor therapy: predictors and the relationship with physical activity.COA of Formula: C26H29Cl2N5O3 And the article contains the following content:

Fatigue is a common side effect of tyrosine kinase inhibitor (TKI) therapy in patients with chronic myeloid leukemia (CML). However, the prevalence of TKI-induced fatigue remains uncertain and little is known about predictors of fatigue and its relationship with phys. activity. In this study, 220 CML patients receiving TKI therapy and 110 genderand age-matched controls completed an online questionnaire to assess fatigue severity and fatigue predictors (Part 1). In addition, phys. activity levels were objectively assessed for 7 consecutive days in 138 severely fatigued and non-fatigued CML patients using an activity monitor (Part 2). We demonstrated that the prevalence of severe fatigue was 55.5% in CML patients and 10.9% in controls (P<0.001). We identified five predictors of fatigue in our CML population: age (odds ratio [OR] 0.96, 95% confidence interval [95% CI]: 0.93-0.99), female gender (OR 1.76, 95% CI: 0.92-3.34), Charlson Comorbidity Index (OR 1.91, 95% CI: 1.16-3.13), the use of comedication known to cause fatigue (OR 3.43, 95% CI: 1.58-7.44), and phys. inactivity (OR of moderately active, vigorously active and very vigorously active compared to inactive 0.43 (95% CI: 0.12-1.52), 0.22 (95% CI: 0.06-0.74), and 0.08 (95% CI: 0.02-0.26), resp.). Objective monitoring of activity patterns confirmed that fatigued CML patients performed less phys. activity of both light (P = 0.017) and moderate to vigorous intensity (P = 0.009). In fact, compared to the non-fatigued patients, fatigued CML patients performed 1 h less of phys. activity per day and took 2,000 fewer steps per day. Our findings facilitate the identification of patients at risk of severe fatigue and highlight the importance of setting reduction of fatigue as a treatment goal in CML care. This study was registered at The Netherlands Trial Registry, NTR7308 (Part 1) and NTR7309 (Part 2). The experimental process involved the reaction of 4-((2,4-Dichloro-5-methoxyphenyl)amino)-6-methoxy-7-(3-(4-methylpiperazin-1-yl)propoxy)quinoline-3-carbonitrile(cas: 380843-75-4).COA of Formula: C26H29Cl2N5O3

The Article related to fatigue cml tyrosine kinase inhibitor therapy phys activity, Mammalian Pathological Biochemistry: Oncology and other aspects.COA of Formula: C26H29Cl2N5O3

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

On March 15, 2021, Chakraborty, Goutam; Patail, Nabeela Khan; Hirani, Rahim; Nandakumar, Subhiksha; Mazzu, Ying Z.; Yoshikawa, Yuki; Atiq, Mohammad; Jehane, Lina E.; Stopsack, Konrad H.; Lee, Gwo-Shu Mary; Abida, Wassim; Morris, Michael J.; Mucci, Lorelei A.; Danila, Daniel; Kantoff, Philip W. published an article.HPLC of Formula: 380843-75-4 The title of the article was Attenuation of SRC kinase activity augments PARP inhibitor-mediated synthetic lethality in BRCA2-altered prostate tumors. And the article contained the following:

Alterations in DNA damage repair (DDR) pathway genes occur in 20%-25% of men with metastatic castration-resistant prostate cancer (mCRPC). Although PARP inhibitors (PARPis) have been shown to benefit men with mCRPC harboring DDR defects due to mutations in BRCA1/2 and ATM, addnl. treatments are necessary because the effects are not durable. We performed transcriptomic anal. of publicly available mCRPC cases, comparing BRCA2 null with BRCA2 wild-type. We generated BRCA2-null prostate cancer cells using CRISPR/Cas9 and treated these cells with PARPis and SRC inhibitors. We also assessed the antiproliferative effects of combination treatment in 3D prostate cancer organoids. We observed significant enrichment of the SRC signaling pathway in BRCA2-altered mCRPC. BRCA2-null prostate cancer cell lines had increased SRC phosphorylation and higher sensitivity to SRC inhibitors (e.g., dasatinib, bosutinib, and saracatinib) relative to wild-type cells. Combination treatment with PARPis and SRC inhibitors was antiproliferative and had a synergistic effect in BRCA2-null prostate cancer cells, mCRPC organoids, and Trp53/Rb1-null prostate cancer cells. Inhibition of SRC signaling by dasatinib augmented DNA damage in BRCA2-null prostate cancer cells. Moreover, SRC knockdown increased PARPi sensitivity in BRCA2-null prostate cancer cells. This work suggests that SRC activation may be a potential mechanism of PARPi resistance and that treatment with SRC inhibitors may overcome this resistance. Our preclin. study demonstrates that combining PARPis and SRC inhibitors may be a promising therapeutic strategy for patients with BRCA2-null mCRPC. The experimental process involved the reaction of 4-((2,4-Dichloro-5-methoxyphenyl)amino)-6-methoxy-7-(3-(4-methylpiperazin-1-yl)propoxy)quinoline-3-carbonitrile(cas: 380843-75-4).HPLC of Formula: 380843-75-4

The Article related to human prostate tumor brca src kinase parp inhibitor, Mammalian Pathological Biochemistry: Oncology and other aspects.HPLC of Formula: 380843-75-4

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

Iurlo, Alessandra; Cattaneo, Daniele; Malato, Alessandra; Accurso, Vincenzo; Annunziata, Mario; Gozzini, Antonella; Scortechini, Anna Rita; Bucelli, Cristina; Scalzulli, Emilia; Attolico, Imma; Maggi, Alessandro; Martino, Bruno; Caocci, Giovanni; Abruzzese, Elisabetta; Pregno, Patrizia; Luciano, Luigiana; Breccia, Massimo published an article in 2020, the title of the article was Low-dose ponatinib is a good option in chronic myeloid leukemia patients intolerant to previous TKIs.SDS of cas: 380843-75-4 And the article contains the following content:

Ponatinib is a potent, orally available, third-generation tyrosine kinase inhibitor (TKI) with proven efficacy in both mutated and unmutated BCR-ABL1-pos. chronic myeloid leukemia (CML) patients including the gatekeeper T315I mutation. While its efficacy has been firstly confirmed in the pivotal phase II PACE trial, nevertheless, when used at the recommended starting dose of 45 mg/d ponatinib raised some concerns due to an increased risk of cardiovascular (CV) adverse events (AEs). In fact, when assessed in a hind limb ischemia model, owing to its multikinase inhibitory properties ponatinib may cause endothelial dysfunction. Ponatinib may affect targets such as VEGFR and promote the expression of proatherogenic surface adhesion receptors. Since these effects were found to be dose-related, suggesting a direct relationship between CV AEs and ponatinib dosage, a reduction of the daily dose has been advised for patients who already achieved at least a major cytogenetic response (MCyR). The experimental process involved the reaction of 4-((2,4-Dichloro-5-methoxyphenyl)amino)-6-methoxy-7-(3-(4-methylpiperazin-1-yl)propoxy)quinoline-3-carbonitrile(cas: 380843-75-4).SDS of cas: 380843-75-4

The Article related to ponatinib chronic myeloid leukemia patient tyrosine kinase inhibitor, Pharmacology: Effects Of Neoplasm Inhibitors and Cytotoxic Agents and other aspects.SDS of cas: 380843-75-4

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

On February 18, 2021, Rousselot, Philippe published an article.COA of Formula: C26H29Cl2N5O3 The title of the article was BiTtEn by Src inhibitors. And the article contained the following:

One ongoing study from the GIMEMA reported the sequential use of dasatinib and blinatumomab as first-line induction and consolidation therapy in Ph1 ALL patients. The complete mol. response rate was up to 60%.5 A few studies reported on the clin. efficacy of TKIs given in combination with blinatumomab. Assi et al reported a retrospective anal. of 12 patients (9 patients with Ph1 ALL including 5 overt relapses and 4 pos. MRD plus 3 chronic myeloid leukemia blast crisis patients including 1 overt relapse and 2 pos. MRD) treated with blinatumomab and ponatinib (n = 8), dasatinib (n = 3), or bosutinib (n = 1). The experimental process involved the reaction of 4-((2,4-Dichloro-5-methoxyphenyl)amino)-6-methoxy-7-(3-(4-methylpiperazin-1-yl)propoxy)quinoline-3-carbonitrile(cas: 380843-75-4).COA of Formula: C26H29Cl2N5O3

The Article related to blinatumomab lymphoblastic leukemia tyrosine kinase src inhibitor, Pharmacology: Effects Of Neoplasm Inhibitors and Cytotoxic Agents and other aspects.COA of Formula: C26H29Cl2N5O3

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