Protein Kinase Inhibitors as Therapeutic Drugs in AML: Advances and Challenges

Abstract

Acute myeloid leukemia (AML) is a malignant blood disorder and the cure rate has been remarkably improved over the past decade. However, recurrent or refractory leukemia remains the major problem of the AML and no clearly effective therapy has been established so far. Traditional treatments such as chemotherapy and hematopoietic stem cell transplantation are both far dissatisfying the patients partly for their individual variety. Besides, conventional treatments usually have many side effects to result in poor prognosis. Therefore, an urgent need is necessary to update therapies of AML. To date, protein kinase inhibitors as new drugs offer hope for AML treatment and many of them are on clinical trials. Here, this review will provide a brief summary of protein kinase inhibitors investigated in AML thus far, mainly including tyrosine protein kinase inhibitors and serine/threonine kinase inhibitors. We also presented the sketch of signal pathways involving protein kinase inhibitors, as well as discussed the clinical applications and the challenges of inhibitors in AML treatment.

Estimating genotoxic effects of anticancer drugs using cytokinesis-block micronucleus assay on human lymphocytes

“…Использование ингибиторов протеинкиназ представляет собой новый и перспективный подход к терапии рака с высокой специфичностью к опухолевым клеткам и меньшей токсичностью для нормальных клеток [22][23][24][25]. Однако результаты исследований генотоксических эффектов действия таких препаратов пока неоднозначны [26].…”

GC / MS characterization and computational kinome‐wide screening of pomegranate fruit extract identifies key phytochemicals interacting to CDK kinases implicated in acute myeloid leukemia cells

“…It is also characterized by immature myeloid lines of blood cells and bone marrow failure (Nepstad et al, 2020). Several targeted kinase inhibitors have been proposed as a therapeutic drug for treating AML cancers (Ling et al, 2017). While these inhibitors show promising effects in controlling AML proliferation, chief disadvantages include huge off‐target side effects of such chemotherapy agents that lead to severe cytotoxicity (Kawase et al, 2019).…”

Glasdegib Dimaleate: Synthesis, Characterization and Comparison of Its Properties with Monomaleate Analogue

“…In recent years, several new therapies for the treatment of AML have appeared. These therapies involve kinase inhibitors (FLT3 inhibitors), IDH1/IDH2 inhibitors, BCL-2 inhibitors, hedgehog inhibitors and others [2][3][4][5][6][7][8][9][10][11][12][13][14][15]. Glasdegib (Figure 1), 1-((2R,4R)-2-(1H-benzo[d]imidazol-2-yl)-1-methylpiperidin-4-yl)-3-(4-cyanophenyl)urea (previously also known as PF-04449913), was developed by Pfizer for the treatment of AML [16][17][18][19].…”