Category: 380843-75-4

On October 31, 2021, Baggio, Diva; Tan, Sean; Porch, Kylie; Shortt, Jake; Ko, Brian published an article.Application of 380843-75-4 The title of the article was Prediction of cardiovascular events in patients with chronic myeloid leukaemia using baseline risk factors and coronary artery calcium scoring. And the article contained the following:

A standardised method for cardiovascular risk stratification in chronic myeloid leukemia patients treated with tyrosine kinase inhibitors is lacking. We report an algorithm for risk stratification applicable to all patients commencing tyrosine kinase inhibitor therapy based on age, prior cardiovascular disease and Framingham Risk Score, incorporating coronary artery calcium scoring in patients at intermediate Framingham Risk Score risk. Of 88 patients retrospectively studied, major adverse cardiovascular event rates in our study-defined low-, intermediate- and high-risk categories were 0%, 10% and 19% resp. Of nine patients down-classified from intermediate to low risk on the basis of coronary artery calcium scoring, none went on to experience a major adverse cardiovascular event. 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).Application of 380843-75-4

The Article related to chronic myeloid leukemia coronary artery calcium algorithm bosutinib, calcium scoring, cardio-oncology, chronic myeloid leukaemia, coronary artery, tyrosine kinase inhibitor and other aspects.Application of 380843-75-4

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

On June 30, 2020, Bruemmendorf, Tim H.; Gambacorti-Passerini, Carlo; Bushmakin, Andrew G.; Cappelleri, Joseph C.; Viqueira, Andrea; Reisman, Arlene; Isfort, Susanne; Mamolo, Carla published an article.Formula: C26H29Cl2N5O3 The title of the article was Relationship between molecular response and quality of life with bosutinib or imatinib for chronic myeloid leukemia. And the article contained the following:

Abstract: Patients with newly diagnosed chronic phase chronic myeloid leukemia (CP CML) can be effectively treated with tyrosine kinase inhibitors (TKIs) and achieve a lifespan similar to the general population. The success of TKIs, however, requires long-term and sometimes lifelong treatment; thus, patient-assessed health-related quality of life (HRQoL) has become an increasingly important parameter for treatment selection. Bosutinib is a TKI approved for CP CML in newly diagnosed adults and in those resistant or intolerant to prior therapy. In the Bosutinib Trial in First-Line Chronic Myelogenous Leukemia Treatment (BFORE), bosutinib demonstrated a significantly higher major mol. response rate compared with imatinib, with maintenance of HRQoL (measured by the Functional Assessment of Cancer Therapy-Leukemia (FACT-Leu) questionnaire), after 12 mo of first-line treatment. We examined relationships between mol. response (MR) and HRQoL. MR values were represented by a log-reduction scale (MRLR; a continuous variable). A repeated-measures longitudinal model was used to estimate the relationships between MRLR as a predictor and each FACT-Leu domain as an outcome. Effect sizes were calculated to determine strength of effects and allow comparisons across domains. The majority of FACT-Leu domains (with the exception of social well-being and phys. well-being) demonstrated a significant relationship with MRLR (p < 0.05). Our results showed variable impact of clin. improvement on different dimensions of HRQoL. For patients who achieved MR5, emotional well-being and leukemia-specific domains showed the greatest improvement, with medium differences in effect sizes, whereas social well-being and phys. well-being had the weakest relationship with MR. 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).Formula: C26H29Cl2N5O3

The Article related to bosutinib imatinib antileukemic agent diagnosis chronic myeloid leukemia, bosutinib, chronic myeloid leukemia, health-related quality of life, imatinib, molecular response and other aspects.Formula: C26H29Cl2N5O3

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

On May 31, 2020, Chow, Amanda; McCrea, Liam; Kimball, Elizabeth; Schaub, Julie; Quigley, Harry; Pitha, Ian published an article.Product Details of 380843-75-4 The title of the article was Dasatinib inhibits peripapillary scleral myofibroblast differentiation. And the article contained the following:

Scleral fibroblast activation occurs in glaucomatous and myopic eyes. Here we perform an unbiased screen to identify kinase inhibitors that reduce fibroblast activation to diverse stimuli in vitro and to in vivo intraocular pressure (IOP) elevation. Primary cultures of peripapillary scleral (PPS) fibroblasts from two human donors were screened using a library of 80 kinase inhibitors to identify compounds that inhibit TGFbeta-induced extracellular matrix (ECM) synthesis. Inhibition of myofibroblast differentiation was verified by alpha smooth muscle actin (aSMA) immunoblot and collagen contraction assay. Three kinase inhibitors were verified to reduce TGFbeta-induced aSMA expression and cellular contractility (rottlerin, PP2, tyrphostin 9). The effect of three Src inhibitors, bosutinib, dasatinib, and SU-6656, on myofibroblast differentiation was evaluated, with only dasatinib significantly inhibiting TGFbeta-induced ECM synthesis, aSMA expression, and cellular contractility at nanomolar dosages. Subconjunctival injection of dasatinib reduced IOP-induced scleral fibroblast proliferation compared to control (4.9 ± 11.1 ng/sclera with 0.1 muM vs. 88.7 ± 38.6 ng/sclera in control, P < 0.0001). Dasatinib inhibits scleral myofibroblast differentiation and there is pharmacol. evidence that this inhibition is not solely due to Src-kinase inhibition. 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).Product Details of 380843-75-4

The Article related to glaucoma peripapillary scleral myofibroblast differentiation dasatinib, fibroblast, fibrosis, glaucoma, kinase inhibitor, peripapillary sclera, scleral remodeling, src kinase and other aspects.Product Details of 380843-75-4

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

On September 30, 2021, Kikuya, Megumi; Furuichi, Kenta; Hirao, Takuya; Endo, Satoshi; Toyooka, Naoki; Ito, Kousei; Aoki, Shigeki published an article.Computed Properties of 380843-75-4 The title of the article was Aldo-keto reductase inhibitors increase the anticancer effects of tyrosine kinase inhibitors in chronic myelogenous leukemia. And the article contained the following:

Tyrosine kinase inhibitors (TKIs) are widely utilized in clin. practice to treat carcinomas, but secondary tumor resistance during chronic treatment can be problematic. AKR1B1 and AKR1B10 of the aldo-keto reductase (AKR) superfamily are highly expressed in cancer cells and are believed to be involved in drug resistance. The aim of this study was to understand how TKI treatment of chronic myelogenous leukemia (CML) cells changes their glucose metabolism and if inhibition of AKRs can sensitize CML cells to TKIs. K562 cells were treated with the TKIs imatinib, nilotinib, or bosutinib, and the effects on glucose metabolism, cell death, glutathione levels, and AKR levels were assessed. To assess glucose dependence, cells were cultured in normal and low-glucose media. Pretreatment with AKR inhibitors, including epalrestat, were used to determine AKR-dependence. Treatment with TKIs increased intracellular glucose, AKR1B1/10 levels, glutathione oxidation, and nuclear translocation of nuclear factor erythroid 2-related factor 2, but with minimal cell death. These effects were dependent on intracellular glucose accumulation. Pretreatment with epalrestat, or a selective inhibitor of AKR1B10, exacerbated TKI-induced cell death, suggesting that especially AKR1B10 was involved in protection against TKIs. Thus, by disrupting cell protective mechanisms, AKR inhibitors may render CML more susceptible to TKI treatments. 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).Computed Properties of 380843-75-4

The Article related to anticancer aldoketo reductase tyrosine kinase inhibitor chronic myelogenous leukemia, akr1b1/10, chronic myelogenous leukemia, epalrestat, glucose, tyrosine kinase inhibitor and other aspects.Computed Properties of 380843-75-4

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

On October 31, 2021, Baggio, Diva; Tan, Sean; Porch, Kylie; Shortt, Jake; Ko, Brian published an article.Application of 380843-75-4 The title of the article was Prediction of cardiovascular events in patients with chronic myeloid leukaemia using baseline risk factors and coronary artery calcium scoring. And the article contained the following:

A standardised method for cardiovascular risk stratification in chronic myeloid leukemia patients treated with tyrosine kinase inhibitors is lacking. We report an algorithm for risk stratification applicable to all patients commencing tyrosine kinase inhibitor therapy based on age, prior cardiovascular disease and Framingham Risk Score, incorporating coronary artery calcium scoring in patients at intermediate Framingham Risk Score risk. Of 88 patients retrospectively studied, major adverse cardiovascular event rates in our study-defined low-, intermediate- and high-risk categories were 0%, 10% and 19% resp. Of nine patients down-classified from intermediate to low risk on the basis of coronary artery calcium scoring, none went on to experience a major adverse cardiovascular event. 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).Application of 380843-75-4

The Article related to chronic myeloid leukemia coronary artery calcium algorithm bosutinib, calcium scoring, cardio-oncology, chronic myeloid leukaemia, coronary artery, tyrosine kinase inhibitor and other aspects.Application of 380843-75-4

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

On June 30, 2020, Bruemmendorf, Tim H.; Gambacorti-Passerini, Carlo; Bushmakin, Andrew G.; Cappelleri, Joseph C.; Viqueira, Andrea; Reisman, Arlene; Isfort, Susanne; Mamolo, Carla published an article.Formula: C26H29Cl2N5O3 The title of the article was Relationship between molecular response and quality of life with bosutinib or imatinib for chronic myeloid leukemia. And the article contained the following:

Abstract: Patients with newly diagnosed chronic phase chronic myeloid leukemia (CP CML) can be effectively treated with tyrosine kinase inhibitors (TKIs) and achieve a lifespan similar to the general population. The success of TKIs, however, requires long-term and sometimes lifelong treatment; thus, patient-assessed health-related quality of life (HRQoL) has become an increasingly important parameter for treatment selection. Bosutinib is a TKI approved for CP CML in newly diagnosed adults and in those resistant or intolerant to prior therapy. In the Bosutinib Trial in First-Line Chronic Myelogenous Leukemia Treatment (BFORE), bosutinib demonstrated a significantly higher major mol. response rate compared with imatinib, with maintenance of HRQoL (measured by the Functional Assessment of Cancer Therapy-Leukemia (FACT-Leu) questionnaire), after 12 mo of first-line treatment. We examined relationships between mol. response (MR) and HRQoL. MR values were represented by a log-reduction scale (MRLR; a continuous variable). A repeated-measures longitudinal model was used to estimate the relationships between MRLR as a predictor and each FACT-Leu domain as an outcome. Effect sizes were calculated to determine strength of effects and allow comparisons across domains. The majority of FACT-Leu domains (with the exception of social well-being and phys. well-being) demonstrated a significant relationship with MRLR (p < 0.05). Our results showed variable impact of clin. improvement on different dimensions of HRQoL. For patients who achieved MR5, emotional well-being and leukemia-specific domains showed the greatest improvement, with medium differences in effect sizes, whereas social well-being and phys. well-being had the weakest relationship with MR. 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).Formula: C26H29Cl2N5O3

The Article related to bosutinib imatinib antileukemic agent diagnosis chronic myeloid leukemia, bosutinib, chronic myeloid leukemia, health-related quality of life, imatinib, molecular response and other aspects.Formula: C26H29Cl2N5O3

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

On July 31, 2022, Szeto, Andy H.; Bucci, Tyler; Deal, Allison; Zhu, Anqi; Ahmad, Majd; Cass, Amanda S.; Sketch, Margaret R.; Kemper, Ryan; Zeidner, Joshua F.; Foster, Matthew C.; Muluneh, Benyam; Crona, Daniel J. 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 Response to Tyrosine Kinase Inhibitors in Real-World Patients With Chronic Myeloid Leukemia. And the article contained the following:

Tyrosine kinase inhibitors (TKIs) are the front-line therapy for chronic myeloid leukemia (CML), where phase 3 clin. trials have demonstrated their safety and efficacy. However, trial patients may not be representative of real-world patients (RWPs). To evaluate RWP clin. factors associated with effectiveness and safety in CML patients treated with TKIs. Patients with CML treated with at least 30 days of imatinib, dasatinib, nilotinib, or bosutinib between 2014 and 2018 were included. Patients were stratified into categories based on the number of factors that would have precluded enrollment into pivotal TKI phase 3 trials (0, 1, ≥2). End points included complete hematol. response (CHR), early mol. response (EMR), major mol. response (MMR), adverse event (AE)-induced dose decreases, treatment interruptions, and treatment discontinuations. Final analyses included 174 patients. Patients with ≥2 factors had a higher risk of dose decreases (relative risk = 1.54; 95% CI = 1.02-2.34; P = 0.02) and a shorter time to dose decrease (hazard ratio = 2.43; 95% CI = 1.23-4.97; P = 0.006) compared with patients with 0 factors. Significant differences were observed in CHR at 1 mo and MMR at 3 mo between patients with 0 and ≥2 factors (P = 0.03 and P = 0.04, resp.). Approx. 60% of our RWPs would have been excluded from the pivotal phase 3 TKI trials. These data suggest that RWPs require more precise dosing to achieve CML clin. milestones and to mitigate AEs, but findings should be validated prospectively. 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 imatinib dasatinib anticancer agent chronic myeloid leukemia adult, adverse drug events, bosutinib, chronic myeloid leukemia, dasatinib, effectiveness, imatinib, nilotinib, real-world patients, tyrosine kinase inhibitors 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

Deb, Suryyani; Boknaes, Niklas; Sjoestroem, Clara; Tharmakulanathan, Anjana; Lotfi, Kourosh; Ramstroem, Sofia published an article in 2020, the title of the article was Varying effects of tyrosine kinase inhibitors on platelet function-A need for individualized CML treatment to minimize the risk for hemostatic and thrombotic complications?.Category: piperazines And the article contains the following content:

Since their introduction, tyrosine kinase inhibitors (TKIs, eg, imatinib, nilotinib, dasatinib, bosutinib, ponatinib) have revolutionized the treatment of chronic myeloid leukemia (CML). However, long-term treatment with TKIs is associated with serious adverse events including both bleeding and thromboembolism. Exptl. studies have shown that TKIs can cause platelet dysfunction. Herein, we present the first side-by-side investigation comparing the effects of currently used TKIs on platelet function and thrombin generation when used in clin. relevant concentrations A flow cytometry multiparameter protocol was used to study a range of significant platelet activation events (fibrinogen receptor activation, alpha granule, and lysosomal exocytosis, procoagulant membrane exposure, and mitochondrial permeability changes). In addition, thrombin generation was measured in the presence of TKIs to assess the effects on global hemostasis. Results show that dasatinib generally inhibited platelet function, while bosutinib, nilotinib, and ponatinib showed less consistent effects. In addition to these general trends for each TKI, we observed a large degree of interindividual variability in the effects of the different TKIs. Interindividual variation was also observed when blood from CML patients was studied ex vivo with whole blood platelet aggregometry, free oscillation rheometry (FOR), and flow cytometry. Based on the donor responses in the side-by-side TKI study, a TKI sensitivity map was developed. We propose that such a sensitivity map could potentially become a valuable tool to help in decision-making regarding the choice of suitable TKIs for a CML patient with a history of bleeding or atherothrombotic disease. 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 bosutinib nilotinib anticancer tyrosine kinase inhibitor platelet myeloid leukemia, chronic myeloid/myelogenous leukemia, coagulation, hemostasis, personalized medicine, platelets, tyrosine kinase inhibitors and other aspects.Category: piperazines

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

On August 31, 2022, Yokoyama, Yuta; Nozawa, Eiji; Morita, Miho; Ishikawa, Emi; Mori, Takehiko; Sakurai, Masatoshi; Kikuchi, Taku; Matsuki, Eri; Yamazaki, Rie; Kataoka, Keisuke; Jibiki, Aya; Kawazoe, Hitoshi; Suzuki, Sayo; Nakamura, Tomonori published an article.Category: piperazines The title of the article was Simultaneous quantification of dasatinib, nilotinib, bosutinib, and ponatinib using high-performance liquid chromatography-Photodiode array detection. And the article contained the following:

Dasatinib, nilotinib, and bosutinib, second-generation tyrosine kinase inhibitors (TKIs), and ponatinib, a third-generation TKI, are approved pharmaceuticals used in the treatment of chronic myeloid leukemia (CML). Although liquid chromatog.-tandem mass spectrometry assays for simultaneous quantification of the four TKIs in human serum have been reported in the literature, a high-performance liquid chromatog. (HPLC) assay that simultaneously quantifies these compounds has not yet been developed. This study aims to establish and validate an efficient HPLC anal. method using a photodiode array (PDA) detector for the simultaneous quantification of the four TKIs. Calibration standards were prepared by serial dilution of serum samples containing the four TKIs, followed by solid-phase extraction The four TKIs were eluted in order within 10 min using a binary HPLC gradient system. The calibration ranges were 2-500 ng/mL for dasatinib, 100-5000 ng/mL for nilotinib, and 10-500 ng/mL for bosutinib and ponatinib. Intra-day and inter-day precision and accuracy values were found to be in accordance with the U. S. Food and Drug Administration guidelines. The recovery rates were 92.9%-96.0%, 80.7%-86.1%, 91.6%-99.0%, and 86.4%-92.6% for dasatinib, nilotinib, bosutinib, and ponatinib, resp. To the best of our knowledge, this is the first report of an HPLC-PDA anal. method that allows efficient simultaneous quantification of the four TKIs in the serum of patients with CML. We believe that the method developed herein can improve the efficiency of therapeutic drug monitoring in patients with CML in clin. practice. 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 photodiode dasatinib nilotinib bosutinib ponatinib high performance liquid chromatog, chronic myeloid leukemia, high-performance liquid chromatography, photodiode array detector, tyrosine kinase inhibitor and other aspects.Category: piperazines

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

On May 31, 2022, Robin, J. B.; Theron, A.; Quittet, P.; Exbrayat, C.; Gaillard, J. B.; Lavabre-Bertrand, T.; David, S.; Saad, A.; Jourdan, E.; Cartron, G. published an article.Application of 380843-75-4 The title of the article was Discontinuation of tyrosine kinase inhibitor in chronic myeloid leukemia: a retrospective cohort in East Occitania. And the article contained the following:

Tyrosine kinase inhibitor (TKI) discontinuation in chronic phase chronic myeloid leukemia (CML) patients has been examined in a real-life setting in the east occitania region of France. We have collected sex, age, prognostic scores, pre-TKI treatment, TKI length and response, relapse data from patients who had stopped TKI in prolonged complete mol. remission (CMR), and analyzed relapse risk factors. Sixty consecutive patients were included from Jan. 2010 to Dec. 2016. Sixteen received pre-TKI treatment. Fifty-three received a first-generation TKI, and seven had a second-generation TKI in first-line therapy. The median TKI time to achieve CMR was 20.5 mo [5-137]. The median TKI length before discontinuation treatment was 73 mo [12-158]. Twenty-two patients (37%) relapsed with a median time to relapse of 6 mo [3-27]. An intermediate or high Sokal score was the only relapse risk factor (HR = 3.32, p < 0.05) associated with relapse after TKI discontinuation. TKI discontinuation was possible without relapse for half of the patients in chronic phase CML. In a real-life cohort, a high-risk Sokal score at diagnosis appears to be an adverse prognosis feature for TKI discontinuation. 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).Application of 380843-75-4

The Article related to chronic myeloid leukemia recurrence tyrosine kinase inhibitor discontinuation france, chronic myeloid leukemia, complete molecular response, molecular recurrence-free remission, tyrosine kinase inhibitor and other aspects.Application of 380843-75-4

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