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https://www.selleckchem.com/products/upadacitinib.html A new series of N-(3,4,5-trimethoxyphenyl)-1H-pyrazolo[3,4-b]pyridin-3-amine derivatives as tubulin polymerization inhibitors were synthesized, and evaluated for the anti-proliferative activities. A structure-activity relationship study revealed that the free amino moiety of 1H-pyrazolo[3,4-b]pyridin-3-amine played an essential role in the anti-proliferative activities. Especially, compound 15c displayed the strongest anti-proliferation against MCF-7 cells with IC50 value of 0.067 ± 0.003 μM, and high selectivity over the normal human embryonic lung WI-38 cells with IC50 value of 23.41 ± 1.53 μM. Further mechanistic studies revealed that 15c showed strong anti-tubulin polymerization activity, changed the morphology of tubulin, and arrested the cell cycle at the G2/M transition in MCF-7 cells. Molecular docking analysis suggested that 15c well occupied the colchicine-binding pocket of tubulin. Additionally, 15c demonstrated anti-angiogenic activities with blocking the migration, invasion and tube formation, disrupting the newly formed tube, and regulating both MMP-9 and TIMP-1 in HUVEC cells. In summary, our results highlight that compound 15c is a potential antitumor compound that are worthy of further development.Drought and heavy metal stress undesirably disturb soil fertility and plant growth. Heavy metals pose severe biological toxic effects. Biochar, a carbon rich source application ameliorates this stress by increasing the plant growth, biomass, nutrient uptake and improves gaseous exchange in drought stress. Application of biochar reduces drought stress by increasing water holding capacity of soil through modification of soil physio-chemical properties that in turn increases water availability to plants and also enhances mineral uptake and regulation of stomatal conductance. Biochar mediates the retention of moisture, nutrients, inhibits harmful bacteria, absorbs heavy metals, pesticides, prevents soil er

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