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Screening for the Potent FMS-Like Tyrosine Kinase 3 (FLT3) Inhibitors from Vietnamese Traditional Herbal Medicines
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| Author:
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HOANG THANH CHI, BUI THI KIM LY
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| Abstract:
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One of the most attractive therapeutic targets found in Acute Myeloid Leukemia (AML) is FMS-like tyrosine
kinase 3 (FLT3). Latest issues with AML diseases are the therapeutic effectiveness of most of these FLT3
inhibitors in patients that tend to be unimpressive, primarily due to their potency and/or adverse effects arising
from their low target selectivity. The discovery and development of novel target FLT3 inhibitors is therefore
also needed. No study has been performed on the screening and detection of FLT3 inhibitors from traditional
Vietnamese herbal medicine. This research may therefore help to increase awareness and recognize novel
potent FLT3 inhibitors, as well as provide new hope for the treatment of AML patients with FLT3
abnormalities, especially in Vietnam. Soxhlet extraction method were used for obtaining ethanol crude extract
of 81 traditional Vietnamese herbal medicine. A protein substrate called glutathione S transferase (GST) fusion
protein is generated, carrying a peptide sequence derived from the human FLT3 (GST-FLT3S)
autophosphorylation site and FLT3-WT/ITD/D835E/D835H were constructed, cloned, expressed and purified.
Western blot was used to track the phosphorylation signal of potent FLT3 inhibitors. GST-FLT3S was inducing
the kinase activity of FLT3-WT/ITD/D835E/D835H in the buffer. Screening results showed that some
medicinal herbs had successfully inhibited the phosphorylation signal caused by the interaction between
isolated GST-FLT3S and FLT3-WT, including the following medicinal materials: Paraboea treubii, Stemona
tuberosa, Milletia pulchra, Oldenlandia diffusa, Jasminum subtriplinerve, Polygonum multiflorum, Lonicera japonica,
Gynura procumbens, Callisia fragrans, Plantago major, Ophiopogon japonicus, Sansevieria cylindrica, Curcuma
aromatica, Aloe vera, Wedelia chinensis, Asparagus cochinchinensis Usticia gendarussa, Ardisia crenata, Cleistocalyx
operculatus, Paramignya trimera, Lantana camara, Vernonia amygdalina.
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| Keyword:
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FMS-like tyrosine kinase 3 (FLT3), Acute myeloid leukemia (AML), traditional Vietnamese herbal medicine.
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| EOI:
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-
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| DOI:
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https://doi.org/10.31838/ijpr/2021.13.02.353
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| Download:
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Request For Article
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