| 产品描述： | KHS101 is a novel inhibitor of transforming acidic coiled-coil protein 3 (TACC3). It is a selective inducer of neuronal differentiation |
| 靶点： |
Microtubule Associated;MicrotubuleAssociated |
| 体外研究： |
KHS101 increased neuronal differentiation of adherently cultured rat NPCs in a dose-dependent fashion (EC50 ∼ 1 μM). KHS101-induced neuron formation (40–60% TuJ1+ cells at 1.5–5 μM KHS101) was also observed under neurosphere-forming conditions in secondary neurospheres derived from both the hippocampus and the subventricular zone (SVZ) of adult rats. SMMC-7721 and SK-Hep-1 cells were cultured with different KHS101 concentrations (40 μM and 20 μM, respectively) to determine the IC50 values. The number and size of spheres were significantly decreased after treatment with KHS101 compared with the control (DMSO) treatment. Sphere formation was dependent on the KHS101 concentration. Bmi1, c-Myc, and Nanog were all decreased in the presence of KHS101. Compared with the control (DMSO), KHS101 decreases the expression of p-AKT, p-GSK3β and β-catenin, as well as the expression of the downstream markers c-Myc and cyclin D1. |
| 体内研究： |
The doses of 6 mg/kg KHS101 (i.v. and s.c.) resulted in reasonable plasma concentrations (>1.5 μM) with a plasma half-life of 1.1–1.4 h, and relative bioavailability of 69% following s.c. dosing. Most importantly, the distribution of KHS101 to the brain was extensive as demonstrated by a brain-to-plasma AUC(0–3h) ratio of ∼8 (dosing: 3 mg/kg KHS101, i.v.) . |
| 细胞实验： |
Rat NPCs were derived and cultured as described previously by others. After hippocampal cell isolation, the number of dissociated cells was determined and ～5 × 10^5 cells were plated in 60-mm uncoated plates. After overnight incubation (37 °C, 5% CO2, and 95% humidity), the medium was changed and the cells were expanded and maintained in an undifferentiated state on polyornithine- (10 μg/mL in water) and laminin-coated (5 μg/mL in PBS;) dishes in DMEM/F12 supplemented with N2 and basic fibroblast growth factor (bFGF, 20 ng/mL;). For KHS101 and shRNA-induction experiments, early passage cells (passaged no more than six times after hippocampal isolation) were trypsinized and plated at a density of ～1,000 cells/cm2 into N2 medium (DMEM/F12 supplemented with N2) containing KHS analogs (e.g., KHS101, KHS92, and NP; SI Text) at different concentrations (0.5–5 μM) or DMSO (0.1%), RA (1–2 μM), BDNF (100 ng/mL), and/or BMP4 (50–100 ng/mL) for 4 d |
| 动物实验： |
Rat NPCs were derived and cultured as described previously by others. After hippocampal cell isolation, the number of dissociated cells was determined and ～5 × 10^5 cells were plated in 60-mm uncoated plates. After overnight incubation (37 °C, 5% CO2, and 95% humidity), the medium was changed and the cells were expanded and maintained in an undifferentiated state on polyornithine- (10 μg/mL in water) and laminin-coated (5 μg/mL in PBS;) dishes in DMEM/F12 supplemented with N2 and basic fibroblast growth factor (bFGF, 20 ng/mL;). For KHS101 and shRNA-induction experiments, early passage cells (passaged no more than six times after hippocampal isolation) were trypsinized and plated at a density of ～1,000 cells/cm2 into N2 medium (DMEM/F12 supplemented with N2) containing KHS analogs (e.g., KHS101, KHS92, and NP; SI Text) at different concentrations (0.5–5 μM) or DMSO (0.1%), RA (1–2 μM), BDNF (100 ng/mL), and/or BMP4 (50–100 ng/mL) for 4 d |
| 参考文献： |
1. Zhou DS, et al. TACC3 promotes stemness and is a potential therapeutic target in hepatocellular carcinoma. Oncotarget. 2015 Sep 15;6(27):24163-77. 2. Wurdak H, et al. A small molecule accelerates neuronal differentiation in the adult rat. Proc Natl Acad Sci U S A. 2010 Sep 21;107(38):16542-7. |
| 溶解性： |
Soluble in DMSO、Ethanol |
| 保存条件： |
-20℃ |
| 配置溶液浓度参考： |
|
1mg |
5mg |
10mg |
| 1 mM |
2.946 ml |
14.729 ml |
29.459 ml |
| 5 mM |
0.589 ml |
2.946 ml |
5.892 ml |
| 10 mM |
0.295 ml |
1.473 ml |
2.946 ml |
| 50 mM |
0.059 ml |
0.295 ml |
0.589 ml |
|
| 注意： |
部分产品我司仅能提供部分信息，我司不保证所提供信息的权威性，仅供客户参考交流研究之用。 |
上海工商
危险品化学品经营许可证（不带存储）
营业执照(三证合一)
北京