PS-1145
(Synonyms: IKK Inhibitor X) 目录号 : GC17603
An IKKβ inhibitor
Cas No.:431898-65-6
Sample solution is provided at 25 µL, 10mM.
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IC50: 88 nM
PS-1145 is an IkappaB kinase (IKK) inhibitor.
The IκB kinase is an enzyme complex involved in propagating the cellular response to inflammation. This enzyme complex is reported to be part of the upstream NF-κB signal transduction cascade.
In vitro: Previous study found that PS-1145 could block TNFalpha-induced NF-kappaB activation in a dose- and time-dependent manner in MM cells, which up-regulated IkappaBalpha protein, enhanced blockade of NF-kappaB activation. In addition, PS-1145 blocked the protective effect of IL-6 against Dex-induced apotosis and TNFalpha-induced ICAM-1 expression was also inhibited by PS-1145. Moreover, PS-1145 inhibited both IL-6 secretion from BMSCs triggered by MM cell adhesion and proliferation of MM cells adherent to BMSCs. However, PS-1145 could only partially inhibit MM cell proliferation. Importantly, it was found that TNFalpha induced MM cell toxicity in the presence of PS-1145 [1]
In vivo: Animal study showed that the intravenous application of PS-1145 could promote direct apoptosis in DMBA-induced skin tumor in male Wistar rats via blocking NF-κB and VEGF activities [2].
Clinical trial: Up to now, PS-1145 is still in the preclinical development stage.
References:
[1] Hideshima T,Chauhan D,Richardson P,Mitsiades C,Mitsiades N,Hayashi T,Munshi N,Dang L,Castro A,Palombella V,Adams J,Anderson KC. NF-kappa B as a therapeutic target in multiple myeloma. J Biol Chem.2002 May 10;277(19):16639-47.
[2] Rajmani RS,Gandham RK,Gupta SK,et al. Administration of IκB-kinase inhibitor PS1145 enhances apoptosis in DMBA-induced tumor in male Wistar rats. Cell Biol Int.2015 Nov;39(11):1317-28.
Cell experiment: | The inhibitory effect of PS-1145 on MM growth is assessed by measuring MTT dye absorbance of the cells. MM.1S cells are cultured for 48 h with 0.2 and 1 ng/mL TNFα, in the absence or presence of 2.5 μM, 5 μM, and 10 μM PS-1145. Cell viability is assessed by MTT assay. Cells from 48 h cultures are pulsed with 10 μL of 5 mg/mL MTT to each well for the last 4 h of 48-h cultures, followed by 100 μL of isopropanol containing 0.04N HCl. Absorbance is measured at 570 nm using a spectrophotometer[1]. |
Animal experiment: | Mice[2]C57BL/6 (B6), B10.BR, and B6.SJL mice are used. Mice receive regular mouse chow and acidified tap water ad libitum. Bortezomib is administered intravenously to animals at a dose of 1 mg/kg, whereas PS-1145 is given intraperitoneally at a dose of 50 mg/kg. The first dose of each agent is administered before conditioning with total body irradiation (TBI).Rats[3]Weight-matched male Wistar rats (320-350 g) are used. Four groups of rats (n=6/group) consume the HFD for a 9-day study period. Animals in each group receive two consecutive icv injections three times/wk. Immediately prior to icv injection of IL-4 (100 ng) or vehicle, all animals receive a pretreatment icv injection of either the IKKβ inhibitor PS1145 (10 μg) or its vehicle (saline). Food intake and body weight are measured daily. Body composition analysis is conducted as above on days 0 and 8. On day 9, animals are euthanized and samples collected. |
References: [1]. Hideshima T, et al. NF-kappa B as a therapeutic target in multiple myeloma. J Biol Chem. 2002 May 10;277(19):16639-47. | |
| Cas No. | 431898-65-6 | SDF | |
| 别名 | IKK Inhibitor X | ||
| 化学名 | N-(6-chloro-9H-pyrido[3,4-b]indol-8-yl)nicotinamide | ||
| Canonical SMILES | ClC1=CC(C2=CC=NC=C2N3)=C3C(NC(C4=CN=CC=C4)=O)=C1 | ||
| 分子式 | C17H11ClN4O | 分子量 | 322.75 |
| 溶解度 | ≥ 32.3mg/mL in DMSO | 储存条件 | Store at -20°C |
| 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。 |
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| 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 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 3.0984 mL | 15.4919 mL | 30.9837 mL |
| 5 mM | 0.6197 mL | 3.0984 mL | 6.1967 mL |
| 10 mM | 0.3098 mL | 1.5492 mL | 3.0984 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。
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Quality Control & SDS
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- Purity: >99.50%
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