Tag: 500-600

On June 30, 2021, Mizuno, Takahito; Sakai, Takamasa; Tanabe, Kouichi; Kozaki, Koji; Umemura, Takumi; Higashikawa, Mariko; Kimura, Tomoki; Yamada, Tetsuya; Goto, Nobuyuki; Ohtsu, Fumiko published an article.Category: piperazines The title of the article was Identification of target small molecule tyrosine kinase inhibitors that need monitoring and clinical application of protocol for early detection of cancer therapeutics-related cardiac dysfunction using signal detection: An investigation of real world data. And the article contained the following:

Purpose: In order to detect cancer therapeutics-related cardiac dysfunction (CTRCD) early, we identified which drugs were to be monitored using signal detection and the package insert, and created and applied a protocol to address this. Methods: Adverse event data recorded in the Japanese Adverse Drug Event Report (JADER) database between Apr. 2004 and Jan. 2018 were used. We applied our findings clin. by creating a protocol to detect CTRCD early. All cases at Tosei General Hospital where the target tyrosine kinase inhibitors were administered from when they were first released in Nov. 2019 were included. We compared the results from before and after we began the protocol to clarify its effects. Results: We found that CTRCD was not described in the serious side-effect section of the package inserts for Bosutinib, Alectinib, and Osimertinib even though CTRCD signals were detected for them. Therefore, it is possible that we may have previously overlooked CTRCD. When we applied our protocol using Osimertinib as the target drug, we were able to detect CTRCD early in 5/21 (24%) patients. Conclusions: It was clarified that the drug identification method used in this study for early detection of adverse events leads to early detection of adverse events when applied clin. 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 cancer cardiac dysfunction tyrosine kinase inhibitor therapeutics side effect, cancer therapeutics-related cardiac dysfunction, japanese adverse drug event report database, osimertinib, small molecule tyrosine kinase inhibitors and other aspects.Category: piperazines

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

Saydam, Guray; Ali, Ridvan; Demir, Ahmet Muzaffer; Eskazan, Ahmet Emre; Guvenc, Birol; Haznedaroglu, Ibrahim Celalettin; Ozcan, Mehmet Ali; Salim, Ozan; Sonmez, Mehmet; Tuglular, Ayse Tulin; Turgut, Mehmet; Unal, Ali; Aver, Birkan; Bozkurt, Sirac; Ozdengulsun, Begum; Ilhan, Osman published an article in 2022, the title of the article was The effect of comorbidities on the choice of tyrosine kinase inhibitors in patients with chronic myeloid leukemia.HPLC of Formula: 380843-75-4 And the article contains the following content:

A review. Tyrosine kinase inhibitors (TKIs) approved for chronic myeloid leukemia known to have similar efficacies but different safety profiles. Therefore, the choice of patient-specific treatments is driven by factors such as tolerability and adverse event profile of TKIs. This review article examines the most up-to-date data and provides practical recommendations for clin. approaches. Nilotinib and ponatinib should be avoided in patients with cardiovascular risk factors, dasatinib in patients with lung damage and bosutinib and nilotinib in patients with liver disease. Considering that certain comorbidities predispose some patients to developing severe adverse events when receiving TKIs, the first- and second-line treatment of chronic myeloid leukemia should be tailored to each patient’s individual condition. 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 review chronic myeloid leukemia comorbidity tki nilotinib ponatinib dasatinib, adverse event, chronic myeloid leukemia, comorbidity, drug toxicity, interactions (drug–drug), safety, tolerability, tyrosine kinase inhibitor and other aspects.HPLC of Formula: 380843-75-4

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

On April 30, 2022, Kumar, Veerandra; Singh, Priyanka; Gupta, Sonu Kumar; Ali, Villayat; Verma, Malkhey published an article.Formula: C26H29Cl2N5O3 The title of the article was Transport and metabolism of tyrosine kinase inhibitors associated with chronic myeloid leukemia therapy: a review. And the article contained the following:

A review. Imatinib, nilotinib, dasatinib, bosutinib, ponatinib, and asciminib are FDA-approved tyrosine kinase inhibitors (TKIs) for chronic myeloid leukemia (CML), each of which has a specific pharmacol. profile. Asciminib has been recently (2021) approved for patients resistant to former TKIs, and because the binding site of this drug (the myristoyl pocket in the ABL1 kinase) is different from that of other TKIs (ATP-binding sites), it is, therefore, effective against T315I mutation of BCR-ABL oncoprotein. All TKIs have a different pharmacol. profile due to different chem. structures. Imatinib is the only TKI whose absorption depends on both influx (OCT1 and OATP1A2) and efflux (ABCB1 and ABCG2) transporters, whereas the others rely only on efflux transporters. The efflux of dasatinib is also regulated by ABCC4 and ABCC6 transporters. Nilotinib and ponatinib are transported passively, as no role of transporters has been found in their case. A phenomenon common to all in the metabolic aspect is that the CYP3A4 isoform of CYP450 primarily metabolizes TKIs. Not only does CYP3A4, flavin-containing monooxygenase 3 (FMO3), and uridine 5′-diphospho-glucuronosyltransferase (UGT) also metabolize dasatinib, and similarly, by glucuronidation process, asciminib gets metabolized by UGT enzymes (UGT1A3, UGT1A4, UGT2B7, and UGT2B17). Addnl., the side effects of TKIs are categorized as hematol. (thrombocytopenia, neutropenia, anemia, and cardiac dysfunction) and non-hematol. (diarrhea, nausea, vomiting, pleural effusion, and skin rash). However, few toxicities are drug-specific, like degradation of biomols. by ponatinib-glutathione (P-GSH) conjugates and clin. pancreatitis (dose-limited toxicity and manageable by dosage alterations) are related to ponatinib and asciminib, resp. This review focuses on the pharmacokinetics of approved TKIs related to CML therapy to comprehend their specificity, tolerability, and off-target effects, which could help clinicians to make a patient-specific selection of CML drugs by considering concomitant diseases and risk factors to the patients. 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 review tyrosine kinase inhibitor metabolism chronic myeloid leukemia therapy, atp-binding cassette (abc) transporters, bcr-abl oncoprotein, cytochrome p450 (cyp450), multidrug resistance, pharmacokinetics, t315i mutation and other aspects.Formula: C26H29Cl2N5O3

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

On April 30, 2020, Wenzel, Tim; Buech, Thomas; Urban, Nicole; Weirauch, Ulrike; Schierle, Katrin; Aigner, Achim; Schaefer, Michael; Kalwa, Hermann published an article.Computed Properties of 380843-75-4 The title of the article was Restoration of MARCK enhances chemosensitivity in cancer. And the article contained the following:

Increased ATP-binding-cassette (ABC) transporter activity is a major cause of chemotherapy resistance in cancer. The ABC transporter family member ABCB1 is often overexpressed in colorectal cancer (CRC). Phosphatidylinositol-4,5-bisphosphat (PI(4,5)P2)-dependent pathways are involved in the regulation of ABCB1 function. The protein Myristoylated Alanine-Rich C-Kinase Substrate (MARCKS) is a pivotal regulator of PI(4,5)P2 and inactivated in many CRC cancers via genetic deletion or hyperphosphorylation. Therefore, MARCKS may critically impact ABCB1. CRC samples as well as CRC cell lines were tested for a connection between MARCKS and ABCB1 via immunofluorescence and Western-blot anal. ABCB1 function was studied via calcein influx assay under treatment with known ABCB1 inhibitors (verapamil, tariquidar) as well as the kinase inhibitor bosutinib. ABCB1 internalization and MARCKS translocation was analyzed via confocal microscopy exploiting the endocytosis inhibitors chlorpromazine and dynasore. Abundance of PI(4,5)P2 was monitored by intramol. fluorescence resonance energy transfer (FRET). Reproductive cell survival was studied via colorimetric WST-1 and clonogenic assays in combination with exposure to the chemotherapeutics doxorubicin and 5-fuorouracil (5-FU). We found increased ABCB1 expression in MARCKS neg. CRC patient tumor samples and established CRC cell lines. Mechanistically, the reconstitution of MARCKS function via recombinant expression or the pharmacol. inhibition of MARCKS phosphorylation led to a substantial decrease in ABCB1 activity. In CRC cells, bosutinib treatment resulted in a MARCKS translocation from the cytosol to the plasma membrane, while simultaneously, ABCB1 was relocated to intracellular compartments. Inhibition of MARCKS phosphorylation via bosutinib rendered cells more sensitive to the chemotherapeutics doxorubicin and 5-FU. Cells devoid of MARCKS function showed incomplete ABCB1 internalization, leading to higher ABCB1 activity enhancing chemoresistance. Vice versa our data suggest the prevention of MARCKS inhibition by reversing hyperphosphorylation or genomic restoration after deletion as two promising approaches to overcome tumor cell resistance towards chemotherapeutic ABCB1 substrates. 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 cancer chemosensitivity marck abc, atp-binding-cassette (abc) transporter, chemotherapy resistance, colorectal cancer, myristoylated alanine-rich c-kinase substrate, p-glycoprotein 1, phosphatidylinositol-4,5-bisphosphat and other aspects.Computed Properties of 380843-75-4

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