| Size | Price | |
|---|---|---|
| 500mg | ||
| 1g | ||
| Other Sizes |
| Targets |
PS-1145 targets the IκB kinase (IKK) complex, with an IC₅₀ of 88 nM in cell-free kinase assays. It demonstrates remarkable selectivity for IKKβ (IC₅₀ = 87 ± 5 nM) over IKKα (IC₅₀ > 100 μM), IKKε (IC₅₀ > 100 μM), and NIK (IC₅₀ > 100 μM). The compound effectively inhibits both basal and induced NF-κB activity by preventing IκBα phosphorylation and degradation.
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|---|---|
| ln Vitro |
PS-1145 demonstrates potent anti-proliferative and pro-apoptotic activity across multiple cancer types. In prostate carcinoma cells, PS-1145 induces caspase 3/7-dependent apoptosis, sensitizes cells to TNFα-induced apoptosis, and inhibits cell proliferation and invasion activity. In multiple myeloma cell lines (MM.1S, U266, RPMI8226), PS-1145 (1.5-50 μM for 48 hours) induces 20-50% proliferative inhibition and blocks IL-6 secretion from bone marrow stromal cells (0.4-10 μM, dose-dependent). In nasopharyngeal carcinoma cells, the IC₅₀ values range from 6.7 to 26.5 μM across different cell lines, with PS-1145 specifically inhibiting tumor cell growth without affecting immortalized normal epithelial cells. PS-1145 also suppresses T-cell alloreactivity in vitro and induces apoptosis, though it is less potent than bortezomib. Mechanistically, PS-1145 down-regulates phosphorylated p65 and IκBα, and decreases expression of downstream targets including Bcl-2, cyclin D1, c-myc, slug, twist, sox9, and EGFR.
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| ln Vivo |
In a DMBA-induced skin tumor rat model, PS-1145 (50 mg/kg, intravenous) enhances tumor cell apoptosis by up-regulating p53, activating caspases, and down-regulating NF-κB and VEGF, thereby inducing tumor progression. In nasopharyngeal carcinoma xenograft models, PS-1145 (3 mg/kg) significantly suppresses subcutaneous tumor formation in nude mice, with C666 xenografts showing greater sensitivity than HONE1. Notably, no apparent adverse effects were observed in the animal studies. In a bone marrow transplantation study, PS-1145 (50 mg/kg, i.p.) showed no early toxicity during prolonged treatment and provided more complete protection against lethal graft-versus-host disease compared to bortezomib.
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| Enzyme Assay |
IKK kinase activity was assessed using partially purified IKK complex obtained from unstimulated HeLa S3 cells, pre-activated using the catalytic domain of MEKK1 expressed in Sf9 cells. Kinase activity was measured using a biotinylated IκBα peptide (250 μM, sequence: RHDSGLDSMKD) and phospho-[Ser32]-phosphoantibodies in an ELISA format with appropriate standard curves for quantification. For Ki measurement of PS-1145, the activated IKK complex was first pre-incubated with varying fixed concentrations of the inhibitor (0.1-1 μM) at 25°C for 1 hour. Apparent Km measurement for MgATP was then performed at each discrete inhibitor concentration. ATP-based kinase assays were also performed using recombinant IKKβ, IKKα, IKKε, and NIK to determine selectivity profiles.
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| Cell Assay |
For cell viability assays, cells were seeded in 96-well plates and treated with serial dilutions of PS-1145 for 48-72 hours. MTT dye (5 mg/mL, 10 μL per well) was added for the last 4 hours of culture, followed by addition of 100 μL isopropanol containing 0.04N HCl. Absorbance was measured at 570 nm using a spectrophotometer. For apoptosis analysis, TUNEL assays were performed to detect DNA fragmentation, and caspase-3/7 activity was measured using fluorogenic substrates. For Western blotting, cells were lysed in RIPA buffer, and protein expression of p65, IκBα, Bcl-2, cyclin D1, c-myc, EGFR, and other targets was analyzed using specific antibodies. Colony formation assays (2D CFA) were performed by plating cells in 6-well plates and treating with PS-1145 (32 μM) for 14 days, followed by crystal violet staining.
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| Animal Protocol |
For nasopharyngeal carcinoma xenograft studies, 1 × 10⁶ HONE1 or C666 cells were injected subcutaneously into the right flanks of 24 nude mice. When tumors reached approximately 100 mm³, mice were divided into control and treatment groups (12 mice per group). The treatment group received PS-1145 at 3 mg/kg via intraperitoneal injection. Tumor volumes were measured twice weekly using calipers, and body weights were monitored for toxicity. For skin tumor studies, male Wistar rats with DMBA-induced skin tumors received PS-1145 at 50 mg/kg via intravenous injection. For bone marrow transplantation studies, PS-1145 was administered at 50 mg/kg via intraperitoneal injection.
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| Toxicity/Toxicokinetics |
In nasopharyngeal carcinoma xenograft studies, PS-1145 (3 mg/kg) showed no apparent adverse effects, with mice maintaining normal body weight and gross appearance throughout the treatment period. In bone marrow transplantation studies, PS-1145 (50 mg/kg, i.p.) showed no early toxicity during prolonged treatment, unlike bortezomib which showed significant toxicity. No other specific toxicity data (LD₅₀, organ toxicity, etc.) were reported.
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| References | |
| Additional Infomation |
PS-1145 (IKK Inhibitor X) is a β-carboline-derived small molecule that has been extensively used as a chemical probe to study the biological functions of the IKK/NF-κB pathway. The compound demonstrates remarkable selectivity for IKKβ over other IKK family members and is >1,000-fold selective over a broad panel of other kinases. In cell-based assays, PS-1145 inhibits TNFα-induced IκBα degradation with an IC₅₀ of 186 ± 8 nM. PS-1145-resistant cell lines have been established, with drug resistance associated with increased levels of active NF-κB p65 and changes in KLF4 expression. The compound should be stored as a powder at -20°C (stable for up to 3 years) and is soluble in DMSO (up to 64 mg/mL).
|
| Molecular Formula |
C17H13CL3N4O
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|---|---|
| Molecular Weight |
395.670320272446
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| Exact Mass |
394.015
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| CAS # |
1049743-58-9
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| PubChem CID |
16219884
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| Appearance |
Typically exists as solid at room temperature
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| LogP |
6.004
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| Hydrogen Bond Donor Count |
4
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| Hydrogen Bond Acceptor Count |
3
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| Rotatable Bond Count |
2
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| Heavy Atom Count |
25
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| Complexity |
448
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| Defined Atom Stereocenter Count |
0
|
| SMILES |
ClC1=CC2=C(NC3=CN=CC=C23)C(NC(C4=CN=CC=C4)=O)=C1.Cl.Cl
|
| InChi Key |
QTDCBADLGJZBHP-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C17H11ClN4O.2ClH/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);2*1H
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| Chemical Name |
N-(6-chloro-9H-pyrido[3,4-b]indol-8-yl)pyridine-3-carboxamide;dihydrochloride
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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 |
| 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) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
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|---|---|
| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.5274 mL | 12.6368 mL | 25.2736 mL | |
| 5 mM | 0.5055 mL | 2.5274 mL | 5.0547 mL | |
| 10 mM | 0.2527 mL | 1.2637 mL | 2.5274 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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