KHS 101 hydrochloride
目录号 : GC13582
neuronal differentiation inducer
Cas No.:1784282-12-7
Sample solution is provided at 25 µL, 10mM.
KHS101 hydrochloride could selectively induce a neuronal differentiation phenotype and interacts with transforming acidic coiled-coil-containing protein 3 (TACC3).
KHS101 increases 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) is also observed under neurosphere-forming conditions in secondary neurospheres derived from both the hippocampus and the subventricular zone (SVZ) of adult rats. Moreover, hippocampal NPCs treated with KHS101 and cultured adherently on microelectrode arrays for 12 d exhibit neuronal morphologies as well as spontaneous spiking activity, hence indicating the presence of functional, maturing neurons[1]. KHS101 markedly attenuates tumor cell growth as compared to the cells treated with the vehicle [dimethyl sulfoxide (DMSO)]. TACC3 is a known target of KHS101 in rodent neural progenitor cells. KHS101 has been shown to cause cellular destabilization of TACC3, hence reducing endogenous TACC3 protein levels over time [2].
Tumor cell proliferation is markedly reduced in KHS101-treated tumors (about twofold). KHS101-treated tumors show signs of elevated cell death (reduced cellularity/increased pyknosis) compared with tumors treated with vehicle control. KHS101 treatment markedly reduces both frontal-to-caudal tumor expansion and corpus callosum invasion of vimentin-positive GBM1 cells. It is also found that the survival of animals carrying GBMX1 tumors (established 2 or 6 weeks before treatment) is markedly increased by the KHS101 treatment regimen for 10 weeks. None of the mice have to be removed from the study because of adverse side effects of the treatment. An additional experiment using a continuous KHS101 treatment regimen until the experimental endpoints also shows a marked increase in the survival of GBMX1-bearing animals. Histological endpoint analysis of KHS101- and vehicle-treated animals confirms a significantly decreased tumor size in KHS101-treated mice[2].
References:
[1]. 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.
[2]. Polson ES, et al. KHS101 disrupts energy metabolism in human glioblastoma cells and reduces tumor growth in mice. Sci Transl Med. 2018 Aug 15;10(454). pii: eaar2718.
Animal experiment: | Rats[2]Xenograft tumors in rats are allowed to establish for 6 weeks after injection of GBM1 cells (1×105 cells) into the forebrain striatum and treated with vehicle or KHS101 for 10 days [6 mg/kg, subcutaneously (sc), twice daily]. To examine whether the observed mitochondrial/redox anomaly is associated with reduced tumor progression, the KHS101 dosing regimen from previous neurogenesis work in rats is adapted using a 10-week tumor treatment strategy (6 mg/kg, sc, twice a day, and biweekly treatment alternating five and three treatment days per week)[2]. |
References: [1]. 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. | |
| Cas No. | 1784282-12-7 | SDF | |
| 化学名 | (E)-6-(isobutylimino)-N-((2-phenylthiazol-4-yl)methyl)-1,6-dihydropyrimidin-2-amine hydrochloride | ||
| Canonical SMILES | CC(C/N=C(N1)\C=CN=C1NCC2=CSC(C3=CC=CC=C3)=N2)C.Cl | ||
| 分子式 | C18H21N5S.HCl | 分子量 | 375.92 |
| 溶解度 | <18.8mg/ml in DMSO; <18.8mg/ml in ethanol | 储存条件 | Desiccate at RT |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
||
| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
 |
1 mg | 5 mg | 10 mg |
| 1 mM | 2.6601 mL | 13.3007 mL | 26.6014 mL |
| 5 mM | 0.532 mL | 2.6601 mL | 5.3203 mL |
| 10 mM | 0.266 mL | 1.3301 mL | 2.6601 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Quality Control & SDS
- View current batch:
- Purity: >99.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet