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The role of FLT3 in haematopoietic malignancies.
FMS-like receptor tyrosine kinase-3; GI MV cells are leukemic cells with a FLT3 kinase mutation. As shown in Figure 6Athe tumor sizes in the LDD group were dramatically smaller than those of the control group. Pratz K, Levis M.
Separation was done on a reverse-phase C 18 column BEH, 1. While the indirubins had a potent kinase inhibitory activity, their poor solubility in water caused some physiological problems.
Cell viability was assessed as described above, and the combination index CI was calculated with the CompuSyn software version 1. Cyclin D1 levels were detected by western blot.
The turbo ion-spray interface was operated at an ion capillary voltage of 3. A pharmacodynamic study of the FLT3 inhibitor KW yields insight into the basis for clinical lsy. Our group previously reported that indirubin analogues potently inhibit FLT3 kinase [ 21 ].
The LDD treatment induced a significant change in the cell cycle populations. The kinase reactions were incubated for 90 min. Incorporating FLT3 inhibitors into acute myeloid leukemia treatment regimens. At day 21 after drug key, mice were sacrificed, and the tumor weights measured B.
The data were analyzed with the BD Accuri C6 software. Imprinting Control Region; IC Blood samples were collected at the indicated time points after the injection.
23221 synthetic procedures for all the compounds are available in the supporting information Supplementary Figures 2—5. The IC 50 s against other kinase activities were also measured Table 1. The signal was measured on an EnVision multi-label reader.
The ability of LDD to suppress tumor cell growth in vivo and in vitro makes it a promising candidate to treat AML patients as well as to possibly treat other types of cancers also. Goat anti-rabbit IgG ; 1;5, and anti-mouse IgG ; 1: Cells were treated with each compound alone and a combination of two compounds.
Midostaurin is a derivative of staurosporine, a pan-kinase inhibitor. We previously reported that a series of 5-substituted indirubin derivatives are 2322 FLT3 inhibitors [ 21 ], which effectively inhibited the 23212 of acute myeloid leukemic cells.
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Analysis of FLT3-activating mutations in patients with acute myelogenous leukemia: Differentiation of leukemic cells was evaluated with Wright-Giemsa staining. Activating mutation of D within the activation loop of FLT3 in human hematologic malignancies.
Several indirubin analogues were synthesized, and their structure activity relationship was investigated Supplementary Table 1.
The pharmacokinetic properties of LDD were investigated Table 3. In terms of clinical application, pulmonary toxicity and interaction with CYP3A4 inhibitor and inducer are major disadvantages of 232211 drug.
The combination index, CI, was measured using the principle based leey Chou et al. Here, we presented the LDD compound which has great potency in vitro and in vivo for antileukemic activity. This result is consistent with the result of the parallel artificial membrane permeability PAMPA assay.