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Purity: ≥98%
PS-1145 (PS1145) is a novel, potent and specific IKK (IκB kinase) inhibitor with anticancer activity. With an IC50 of 88 NM, it inhibits IKK. In rats with DMBA-induced skin tumors, PS 1145 has excellent in vivo antitumor efficacy.
| Targets |
IKK (IC50 = 88 nM)
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| ln Vitro |
PS-1145 inhibits IkappaBalpha phosphorylation, which prevents TNFalpha from activating NF-kappaB, and it also prevents IL-6 from protecting against Dex-induced apotosis. Additionally, PS-1145 reduces IL-6 secretion from BMSCs stimulated by MM cell adhesion as well as paracrine MM cell growth. [1] By activating CD3 and CD28 coreceptors in human primary CD4(+) T cells, PS-1145 prevents cell proliferation and hinders the activation of NF-κB and AP-1 transcription factors. [2]
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| ln Vivo |
PS-1145 (50 mg/kg, i.v.) promotes tumor cell apoptosis in male Wistar rats with DMBA-induced skin tumors by up-regulating p53, activating caspases, and down-regulating NF-κB and VEGF factor, and this promotes the growth of the tumor. [3]
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| Enzyme Assay |
PS-1145 is dissolved in DMSO and kept at −20 °C until use. By measuring Km, ATP against changing fixed inhibitor concentrations, the Ki value of PS-1145 against the IKK complex is calculated. In a nutshell, the catalytic domain of MEKK1 expressed in sf9 is used to pre-activate the partially purified IKK complex obtained from unstimulated HeLa S3 cells. An ELISA format is used to measure kinase activity using a biotinylated IκBα peptide (250 μM, RHDSGLDSMKD,Km,peptide = 30 M,K m, ATP = 10 μM) and phospho-[Ser32]-phosphoantibodies.
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| Cell Assay |
By measuring the cells' MTT dye absorbance, the inhibitory effect of PS-1145 on MM growth is determined. For the final 4 hours of 48-h cultures, cells from 48-h cultures are pulsed with 10 μL of 5 mg/ml MTT to each well, and then 100 l of isopropanol containing 0.04N HCl. Using a spectrophotometer, absorbance is measured at 570 nm.
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| Animal Protocol |
Mice: The mice used are C57BL/6 (B6), B10.BR, and B6.SJL. Regular mouse food and acidified tap water are freely given to mice. PS-1145 is given intraperitoneally at a dose of 50 mg/kg, whereas animals receive bortezomib intravenously at a dose of 1 mg/kg. Before conditioning with total body irradiation (TBI), the first dose of each agent is given.
Rats: Male Wistar rats weighing between 320 and 350 g are employed. For a 9-day research period, the HFD is consumed by four groups of rats (n=6/group). Three times per week, each group's animals receive two consecutive icv injections. All animals receive a pretreatment icv injection of either the IKK inhibitor PS1145 (10 g) or its vehicle (saline) just before receiving an icv injection of IL-4 (100 ng) or vehicle. Daily measurements of food intake and body weight are taken. On days 0 and 8, body composition analysis is performed as described above. Animals are put to death and samples are taken on day nine. |
| References | |
| Additional Infomation |
N-(6-chloro-9H-pyrido[3,4-b]indol-8-yl)-3-pyridinecarboxamide is a member of beta-carbolines.
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| Molecular Formula |
C17H11CLN4O
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|---|---|---|
| Molecular Weight |
322.75
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| Exact Mass |
322.062
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| Elemental Analysis |
C, 63.26; H, 3.44; Cl, 10.98; N, 17.36; O, 4.96
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| CAS # |
431898-65-6
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| Related CAS # |
PS-1145 dihydrochloride;1049743-58-9
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| PubChem CID |
9949093
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| Appearance |
Yellow solid powder
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| Density |
1.5±0.1 g/cm3
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| Boiling Point |
511.0±50.0 °C at 760 mmHg
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| Flash Point |
262.9±30.1 °C
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| Vapour Pressure |
0.0±1.3 mmHg at 25°C
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| Index of Refraction |
1.810
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| LogP |
3.53
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
3
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| Rotatable Bond Count |
2
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| Heavy Atom Count |
23
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| Complexity |
448
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| Defined Atom Stereocenter Count |
0
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| SMILES |
ClC1C([H])=C(C2=C(C=1[H])C1C([H])=C([H])N=C([H])C=1N2[H])N([H])C(C1=C([H])N=C([H])C([H])=C1[H])=O
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| InChi Key |
JZRMBDHPALEPDM-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C17H11ClN4O/c18-11-6-13-12-3-5-20-9-15(12)21-16(13)14(7-11)22-17(23)10-2-1-4-19-8-10/h1-9,21H,(H,22,23)
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| Chemical Name |
N-(6-chloro-9H-pyrido[3,4-b]indol-8-yl)pyridine-3-carboxamide
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| Synonyms |
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
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| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: 2.08 mg/mL (6.44 mM) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), suspension solution; with sonication.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.08 mg/mL (6.44 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 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 |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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