Latest Research News on Imatinib: Dec – 2019

Overriding Imatinib Resistance with a Novel ABL Kinase Inhibitor

Resistance to the ABL enzyme matter imatinib (STI571 or Gleevec) in chronic chronic myelocytic leukemia (CML) happens through choice for neoplasm cells harboring BCR-ABL enzyme domain purpose mutations that interfere with drug binding. Crystallographic studies predict that almost all imatinib-resistant mutants ought to stay sensitive to inhibitors that bind ABL with less demanding conformational needs. BMS-354825 is AN orally bioavailable ABL enzyme matter with two-log hyperbolic efficiency relative to imatinib that retains activity against fourteen of fifteen imatinib-resistant BCR-ABL mutants. BMS-354825 prolongs survival of mice with BCR-ABL–driven unwellness and inhibits proliferation of BCR-ABL–positive bone marrow antecedent cells from patients with imatinib-sensitive and imatinib-resistant CML. [1]

Clinical Pharmacokinetics of Imatinib

Imatinib may be a potent and selective substance of the macromolecule amino acid enzyme Bcr-Abl, platelet-derived protein receptors (PDGFRα and PDGFRβ) and KIT. Imatinib is approved for the treatment of chronic myeloid cancer (CML) and epithelial duct stromal growth (GIST), that have dysregulated activity of associate imatinib-sensitive enzyme because the underlying pathogenetic feature. [2]

Dasatinib in Imatinib-Resistant Philadelphia Chromosome–Positive Leukemias

BACKGROUND: The BCR-ABL amino acid enzyme matter imatinib is effective in city chromosome–positive (Ph-positive) leukemias, however relapse happens, principally as a results of the outgrowth of leukemic subclones with imatinib-resistant BCR-ABL mutations. we tend to evaluated dasatinib, a BCR-ABL matter that targets most imatinib-resistant BCR-ABL mutations, in patients with chronic myelogenous malignant neoplastic disease (CML) or Ph-positive acute lymphocytic leukemia (ALL).

METHODS: Patients with varied parts of CML or with Ph-positive ALL World Health Organization couldn’t tolerate or were proof against imatinib were listed in an exceedingly phase one dose-escalation study. Dasatinib (15 to 240 mg per day) was administered orally in four-week treatment cycles, once or doubly daily. [3]

Hyaluronan abrogates imatinib-induced senescence in chronic myeloid leukemia cell lines

Hyaluronan (HA) is that the main glycosaminoglycan of the animate thing matrix. CD44 is that the most significant HA receptor, and each are related to poor prognosis in cancer. Chronic cancer of the blood|chronic myelocytic leukemia|myelocytic leukemia|granulocytic leukemia|chronic leukemia} (CML) is characterised by the presence of a constitutively activated aminoalkanoic acid enzyme (Breakpoint Cluster Region – Abelson murine leukemia infective agent gene homolog1, BCR-ABL). it’s primarily treated with BCR-ABL inhibitors, like imatinib. However, the choice of resistant cells results in treatment failure. The aim of this work was to work out the capability of HA (high molecular weight) to counteract the result of imatinib in human CML cell lines (K562 and Kv562). [4]

Protective Potential of Grape Seed Proanthocyandins Extract against Glivec (Imatinib Mesylate) Induced Liver Toxicity and Oxidative Stress in Male Rats

Objectives: Glivec (Imatinib mesylate) AN antineoplastic therapy agent utilized in the treatment of the many forms of cancer. this study examines the hepatoprotective potential of grape seed proanthocyandins extract (GSPE) against Glivec evoked aerophilic stress and toxicity in male unusual person rats.

Materials and Methods: a complete of forty male unusual person rats were equally divided into four clusters; group one was management, cluster a pair of was GSPE cluster (rats received orally GSPE by abdomen tube  for four week), cluster three was Glivec cluster (rats were injected intraperitoneally with Glivec  for four weeks) and cluster four was rats treated with GSPE and Glivec for four weeks. [5]

Reference

[1] Shah, N.P., Tran, C., Lee, F.Y., Chen, P., Norris, D. and Sawyers, C.L., 2004. Overriding imatinib resistance with a novel ABL kinase inhibitor. Science, 305(5682), (Web Link)

[2] Peng, B., Lloyd, P. and Schran, H., 2005. Clinical pharmacokinetics of imatinib. Clinical pharmacokinetics, 44(9), (Web Link)

[3] Talpaz, M., Shah, N.P., Kantarjian, H., Donato, N., Nicoll, J., Paquette, R., Cortes, J., O’Brien, S., Nicaise, C., Bleickardt, E. and Blackwood-Chirchir, M.A., 2006. Dasatinib in imatinib-resistant Philadelphia chromosome–positive leukemias. New England Journal of Medicine, 354(24), (Web Link)

[4] Hyaluronan abrogates imatinib-induced senescence in chronic myeloid leukemia cell lines
Silvina Lompardía, Mariángeles Díaz, Matías Pibuel, Daniela Papademetrio, Daniela Poodts, Cintia Mihalez, Élida Álvarez & Silvia Hajos
Scientific Reports volume 9, (Web Link)

[5] Al-Rasheed, N. M., El-Masry, T. A., Tousson, E., Hassan, H. M. and Al-Ghadeer, A. (2017) “Protective Potential of Grape Seed Proanthocyandins Extract against Glivec (Imatinib Mesylate) Induced Liver Toxicity and Oxidative Stress in Male Rats”, Annual Research & Review in Biology, 20(6), (Web Link)