PS-1145 (Synonyms: IKK Inhibitor X) |
Catalog No.GC17603
One-Click Copy Product Info
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IKK inhibitor
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 431898-65-6
Sample solution is provided at 25 µL, 10mM.
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 | |
| Synonyms | IKK Inhibitor X | ||
| Chemical Name | 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 | ||
| Formula | C17H11ClN4O | M.Wt | 322.75 |
| Solubility | ≥ 32.3mg/mL in DMSO | Storage | Store at -20°C |
| General tips | Please select the appropriate solvent to prepare the stock solution according to the
solubility of the product in different solvents; once the solution is prepared, please store it in
separate packages to avoid product failure caused by repeated freezing and thawing.Storage method
and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored
at -20°C, please use it within 1 month. To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time. |
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| Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. | ||
| Prepare stock solution | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 3.0984 mL | 15.4919 mL | 30.9837 mL |
| 5 mM | 619.7 μL | 3.0984 mL | 6.1967 mL |
| 10 mM | 309.8 μL | 1.5492 mL | 3.0984 mL |
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Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL saline, mix and clarify.
Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.
Note: 1. Please make sure the liquid is clear before adding the next solvent.
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3. All of the above co-solvents are available for purchase on the GlpBio website.
Quality Control & SDS
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- Purity: >99.50% Appearance: A solid
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- SDS (Safety Data Sheet)
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Average Rating: 5 (Based on Reviews and 38 reference(s) in Google Scholar.)