Nocodazole (Oncodazole) 是快速可逆的microtubule抑制剂。 Nocodazole与β-微管蛋白结合并破坏微管组装/拆卸动力学,从而防止有丝分裂并诱导肿瘤细胞凋亡。Nocodazole 抑制Bcr-Abl,增强CRISPR/Cas9的活性。
生物活性 | Nocodazole (Oncodazole) is a rapidly-reversible inhibitor ofmicrotubule. Nocodazole binds to β-tubulin and disrupts microtubule assembly/disassembly dynamics, which prevents mitosis and inducesapoptosisin tumor cells. Nocodazole inhibitsBcr-Abl, and activatesCRISPR/Cas9. |
IC50& Target[1] | Abl 91 nM (Kd) | ABL(E255K) 120 nM (Kd) | ABL(T315I) 170 nM (Kd) | BRAF 1.8 μM (Kd) | BRAF(V600E) 1.1 μM (Kd) | c-KIT 1.6 μM (Kd) | MEK1 1.7 μM (Kd) | MEK2 1.6 μM (Kd) | MET 1.7 μM (Kd) | PI3Kγ 1.5 μM (Kd) | Microtubule/Tubulin | CRISPR/Cas9 |
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体外研究 (In Vitro) | Nocodazole exhibits good affinity toward c-KIT, with a Kdvalue of 1.6 μM in highly malignant human cancer cells. Nocodazole displays good binding affinity toward the components of the mitogen-activated protein kinase (MAPK) pathway, such as BRAF (Kd=1.8 μM), BRAF(V600E) (Kd=1.1 μM), MEK1 (Kd=1.7 μM), and MEK2 (Kd=1.6 μM)[1]. Nocodazole has the highest affinity for αβIVand the lowest affinity for αβIII[2]. Nocodazole (1 nM) induces apoptosis of COLO 205 cancer cells[3]. Nocodazole (≥ 30 μg/mL) significantly increases the percentage of annexin-V-binding cells without significantly modifying average forward scatter of human erythrocytes[4]. In CHO cells, the addition of 1 nM Nocodazole, a concentration that suppresses microtubule dynamics, slows migration and increases the frequency and duration of resting states, but the directionality of the cells is maintained. In contrast to the effects of the low drug concentration, the addition of 70 nM Nocodazole, a concentration that eliminates the microtubule network, causes cells to move much more randomly, i.e., the directionality of the cells toward the wound is lost[6].
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体内研究 (In Vivo) | Nocodazole (5 mg/kg/three times per week, i.p.) has antitumor effects in athymic mice bearing COLO 205 tumor xenografts. Nocodazole (1 nM) + R-41400 dramatically increase the levels of p21/CIP1 and p27/KIP1 protein in the tumor tissues[3].
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运输条件 | Room temperature in continental US; may vary elsewhere. |
储存方式 | Powder | -20°C | 3 years | | 4°C | 2 years | In solvent | -80°C | 6 months | | -20°C | 1 month |
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溶解性数据 | In Vitro: DMSO : 20 mg/mL(66.37 mM;Need ultrasonic) 配制储备液 1 mM | 3.3187 mL | 16.5937 mL | 33.1873 mL | 5 mM | 0.6637 mL | 3.3187 mL | 6.6375 mL | 10 mM | 0.3319 mL | 1.6594 mL | 3.3187 mL |
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