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