Tag: 500-600

Fu, Yuna; Wang, Jianhua; Wang, Yan; Sun, Heng published an article in 2022, the title of the article was Investigating the Effect of Tyrosine Kinase Inhibitors on the Interaction between Human Serum Albumin by Atomic Force Microscopy.Category: piperazines And the article contains the following content:

It is important for elucidating the regulation mechanism of life activities, as well as for the prevention, diagnosis, and drug design of diseases, to study protein-protein interactions (PPIs). Here, we investigated the interactions of human serum albumin (HSA) in the presence of tyrosine kinase inhibitors (TKIs: imatinib, nilotinib, dasatinib, bosutinib, and ponatinib) using at. force microscopy (AFM). The distribution of rupture events including the specific interaction force Fi and the non-specific interaction force F0 between HSA pairs was analyzed. Based on the force measurements, Fi and F0 between HSA pairs in the control experiment were calculated to be 47 ± 1.5 and 116.1 ± 1.3 pN. However, Fi was significantly decreased in TKIs, while F0 was slightly decreased. By measuring the rupture forces at various loading rates and according to the Bell equation, the kinetic parameters of the complexes were investigated in greater detail. Mol. docking was used as a complementary means by which to explore the force of this effect. The whole measurements indicated that TKIs influenced PPIs in a variety of ways, among which hydrogen bonding and hydrophobic interactions were the most important. In conclusion, these outcomes give us a better insight into the mechanisms of PPIs when there are exogenous compounds present as well as in different liquid environments. 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).Category: piperazines

The Article related to tyrosine kinase inhibitor serum albumin atomic force microscopy, atomic force microscopy, human serum albumin, protein–protein interactions, tyrosine kinase inhibitors, Placeholder for records without volume info and other aspects.Category: piperazines

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

Kazim, Noor; Yen, Andrew published an article in 2021, the title of the article was Evidence of off-target effects of bosutinib that promote retinoic acid-induced differentiation of non-APL AML cells.Safety of 4-((2,4-Dichloro-5-methoxyphenyl)amino)-6-methoxy-7-(3-(4-methylpiperazin-1-yl)propoxy)quinoline-3-carbonitrile And the article contains the following content:

In the present study, we determined the effects of the Src family kinase (SFK) inhibitor, Bosutinib, and the engineered loss of the Lyn SFK on all-trans retinoic acid-induced leukemic cell differentiation. Retinoic acid (RA) is an embryonic morphogen and dietary factor that demonstrates chemotherapeutic efficacy in inducing differentiation of a non-APL AML cell model, the HL-60 human myeloblastic (FAB-M2) leukemia cell line, via activation of a novel signalsome containing an ensemble of signaling mols. that drive differentiation. Bosutinib is an inhibitor of SFKs used to treat myeloid leukemias where prominent high expression of SFKs, in particular Lyn, has been observed Using either Bosutinib or loss of Lyn expression due to shRNA promoted RA-induced phenotypic differentiation, G0 arrest, and respiratory burst (functional differentiation) of HL-60 cells. Signaling events putatively seminal to RA-induced differentiation, the expression of Fgr, Cbl, Slp-76 and Vav, and the phosphorylation of c-Raf (pS259), Vav (p-tyr), and Slp76 (p-tyr) were not inhibited by Bosutinib or loss of Lyn. Nor was RA-induced upregulation of p-tyr phosphorylation of p47phox, a member of the NADPH complex that produces ROS, a putative phosphorylation dependent signaling regulator. Surprisingly, Bosutinib still works in the absence of Lyn to enhance RA-induced differentiation and neither compromised RA-induced expression, nor phosphorylation of signaling mols. that drive differentiation. These findings suggested there is a novel, off-target, Lyn-independent effect of Bosutinib that is of therapeutic significance to differentiation 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).Safety of 4-((2,4-Dichloro-5-methoxyphenyl)amino)-6-methoxy-7-(3-(4-methylpiperazin-1-yl)propoxy)quinoline-3-carbonitrile

The Article related to bosutinib retinoic acid phosphorylation, acute myeloid leukemia (aml), lyn, bosutinib, cell differentiation, retinoic acid (ra), src family kinase (sfk) inhibitor, Placeholder for records without volume info and other aspects.Safety of 4-((2,4-Dichloro-5-methoxyphenyl)amino)-6-methoxy-7-(3-(4-methylpiperazin-1-yl)propoxy)quinoline-3-carbonitrile

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

On December 31, 2021, Smith, Stephanie M.; Sabnis, Himalee S.; Lewis, Rebecca Williamson; Effinger, Karen E.; Bergsagel, John; Patterson, Briana; Mertens, Ann; Sakamoto, Kathleen M.; Schapira, Lidia; Castellino, Sharon M. published an article.SDS of cas: 380843-75-4 The title of the article was Patterns of surveillance for late effects of BCR-ABL tyrosine kinase inhibitors in survivors of pediatric Philadelphia chromosome positive leukemias. And the article contained the following:

Targeted anticancer therapies such as BCR-ABL tyrosine kinase inhibitors (TKIs) have improved outcomes for chronic myeloid leukemia (CML) and Philadelphia chromosome-pos. acute lymphoblastic leukemia (Ph + ALL). However, little is known about long-term risks of TKIs in children. Exposure-based survivorship guidelines do not include TKIs, thus surveillance practices may be variable. We retrospectively examined surveillance for cardiac and endocrine late effects in children receiving TKIs for Ph + leukemias, diagnosed at < 21 years between 2000 and 2018. Frequency of echocardiogram (ECHO), ECG (ECG), TSH (TSH), dual-energy x-ray absorptiometry (DXA), and bone age testing were abstracted. Descriptive statistics were stratified by leukemia type. 66 Patients (CML n = 44; Ph + ALL n = 22) met inclusion criteria. Among patients with CML, ≥1 evaluation was done: ECHO (50.0%), ECG (48.8%), TSH (43.9%), DXA (2.6%), bone age (7.4%). Among patients with Ph + ALL, ≥1 evaluation was done: ECHO (86.4%), ECG (68.2%), TSH (59.1%), DXA (63.6%), bone age (44.4%). Over a median 6.3 and 5.7 years of observation, resp., 2% of patients with CML and 57% with Ph + ALL attended a survivorship clinic. Despite common exposure to TKIs in survivors of Ph + leukemias, patterns of surveillance for late effects differed in CML and Ph + ALL, with the latter receiving more surveillance likely due to concomitant chemotherapy exposures. Targeted therapies such as TKIs are revolutionizing cancer treatment, but surveillance for late effects and referral to survivorship clinics are variable despite the chronicity of exposure. Evidence based guidelines and longer follow-up are needed. 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 tyrosine kinase inhibitor pediatric philadelphia chromosome leukemia, bcr-abl leukemia, cml, late-effects, ph + all, surveillance, tyrosine kinase inhibitors, Placeholder for records without volume info and other aspects.SDS of cas: 380843-75-4

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

On February 29, 2020, Okano, Hideyuki; Yasuda, Daisuke; Fujimori, Koki; Morimoto, Satoru; Takahashi, Shinichi published an article.Quality Control of 4-((2,4-Dichloro-5-methoxyphenyl)amino)-6-methoxy-7-(3-(4-methylpiperazin-1-yl)propoxy)quinoline-3-carbonitrile The title of the article was Ropinirole, a New ALS Drug Candidate Developed Using iPSCs. And the article contained the following:

A review. Induced pluripotent stem cells (iPSCs) are increasingly used in the study of disease mechanisms and the development of effective disease-modifying therapies for neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS). Recently, three candidate anti-ALS drugs-ropinirole (ROPI), retigabine, and bosutinib-have been identified in iPSC-based drug screens and are now being evaluated in clin. trials for safety and effectiveness. We review the preclin. data, clin. research design, and rationale for ROPI as an anti-ALS drug candidate compared with those of the other two drugs. We also discuss the use of iPSCs for understanding and monitoring treatment response as well as for new insights into the development of new drugs and therapeutic interventions for major neurodegenerative diseases. 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).Quality Control of 4-((2,4-Dichloro-5-methoxyphenyl)amino)-6-methoxy-7-(3-(4-methylpiperazin-1-yl)propoxy)quinoline-3-carbonitrile

The Article related to ropinirole als drug candidate ipscs review, amyotrophic lateral sclerosis, disease modeling, drug repositioning, induced pluripotent stem cells, ropinirole, Placeholder for records without volume info and other aspects.Quality Control of 4-((2,4-Dichloro-5-methoxyphenyl)amino)-6-methoxy-7-(3-(4-methylpiperazin-1-yl)propoxy)quinoline-3-carbonitrile

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

Saussele, Susanne; Kohlbrenner, Katharina; Vogelmann, Tobias; Schubert, Tino published an article in 2022, the title of the article was Incidence, Prevalence, and Real-World Treatment Patterns in Chronic Myeloid Leukemia: Results from a Population-Representative German Claims Data Analysis.COA of Formula: C26H29Cl2N5O3 And the article contains the following content:

Real-world data on usage of 1st-, 2nd-, and 3rd-generation tyrosine kinase inhibitor (TKI) in chronic myeloid leukemia (CML) are scarce. This study therefore aimed to analyze the use of different TKIs used in 1st- and 2nd-line treatment and the frequency of TKI switches in CML. This observational study was based on the InGef research database, an anonymized representative claims dataset in Germany (n = 4 million). An incidence and prevalence patient CML cohort was followed for 5 and 3 years. Analyses regarding incidence, prevalence, and therapy distribution were performed descriptively. 151 Patients were included in the incidence and 636 patients in the prevalence cohort. This resulted in an incidence of 1.8 (95% confidence interval [CI]: 1.34-2.20) and a prevalence of 14.9 (95% CI: 13.70-16.03) per 100,000 inhabitants. For the incidence cohort, data on 1st-line therapy were available for 124 patients and distributed across imatinib (N = 52), nilotinib (N = 44), dasatinib (N = 12), chemotherapies as hydroxycarbamide (N = 11), and ponatinib/bosutinib (N = 5). Twenty-six percent of patients switched TKI therapy at least once in 3 years. In the prevalence cohort, 423 patients (66.5%) had claims on existing or newly emerged cardiovascular diseases (CDs). No significant differences (p = 0.32) between TKIs in patients with CD were found. Every fourth patient switched TKI therapy within the first 3 years after treatment initiation. Switches were more likely when hints of disease progression or intolerability were observable in the database. 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 human disease progression chronic myeloid leukemia, chronic myeloid leukemia, chronic myeloid leukemia, claims data analysis, real-world evidence, tki, Placeholder for records without volume info and other aspects.COA of Formula: C26H29Cl2N5O3

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

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