| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 25mg |
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| Other Sizes |
| Targets |
human PKCβ1:21 nM (IC50)
>human PKCβ2:5 nM (IC50) PKCα:331 nM (IC50) Protein kinase C beta (PKCβ), specifically the PKCβ1 and PKCβ2 isoforms. PKCβ is a member of the protein kinase C family of serine/threonine kinases that are activated by diacylglycerol (DAG) and calcium ions. PKCβ plays pivotal roles in multiple signaling pathways, including those regulating cell proliferation, differentiation, apoptosis, angiogenesis, and insulin signaling. The PKCβ inhibitor acts as an ATP-competitive inhibitor, binding to the ATP-binding pocket of the kinase domain, thereby preventing phosphorylation of downstream substrates. The compound demonstrates potent inhibition of human PKCβ1 with an IC50 of 21 nM and human PKCβ2 with an IC50 of 5 nM. It exhibits remarkable selectivity, being at least 60-fold more selective for PKCβ over other PKC isozymes such as PKCα, PKCγ, and PKCε. This high degree of selectivity is crucial for minimizing off-target effects and enabling precise mechanistic studies. The compound's selectivity profile also distinguishes it from other PKC inhibitors that may have broader isoform inhibition. By selectively inhibiting PKCβ, the compound allows researchers to specifically investigate the role of this kinase in various physiological and pathological processes. PKCβ has been implicated in diabetic complications, including diabetic nephropathy, retinopathy, and neuropathy, as well as in cancer progression, angiogenesis, and cardiovascular diseases. |
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| ln Vitro |
In a time- and dose-dependent way, PKCβ inhibitor 1 (0-30 μM; 48 hours) inhibits the growth of tumor cells[2]. Induction of apoptosis in 2F7 cells is caused by PKCβ inhibitor 1 (14 μM; 2-48 hours). Cell cycle progression in 2F7 and BCBL-1 cells is inhibited by PKCβ inhibitor 1 (15 μM; 2-48 hours)[2]. The expression of phospho-PKCβ in BCBL-1 and 2F7 cells is decreased by PKCβ (15 or 14 μM, respectively; 2-48 hours) inhibitor 1[2]. Supressing GSK3β, mTOR, and S6 phosphorylation is the effect of PKCβ inhibitor 1 (0–48 hours)[2].
In enzymatic assays, the PKCβ inhibitor demonstrates potent inhibition of human PKCβ1 with an IC50 of 21 nM and human PKCβ2 with an IC50 of 5 nM. The compound exhibits remarkable selectivity, being at least 60-fold more selective for PKCβ over other PKC isozymes such as PKCα, PKCγ, and PKCε. This selectivity is demonstrated in kinase profiling panels where the compound shows minimal activity against a broad range of other kinases. The compound's ATP-competitive mechanism of action is confirmed through kinetic studies showing competition with ATP. In cell-based assays, the PKCβ inhibitor effectively blocks PKCβ-mediated signaling pathways, as demonstrated by reduced phosphorylation of downstream substrates. The compound's potency and selectivity make it a valuable tool for studying PKCβ function in various cellular contexts. It has been used to investigate the role of PKCβ in diabetic complications, where inhibition of PKCβ has been shown to ameliorate pathological changes in animal models. The compound has also been used in cancer research to study the role of PKCβ in tumor growth, angiogenesis, and metastasis. In addition, the PKCβ inhibitor has been employed in cardiovascular research to study the role of PKCβ in cardiac function and ischemic injury. |
| ln Vivo |
The in vivo activity of the PKCβ inhibitor has been evaluated in various animal models. Studies have demonstrated that PKCβ inhibition can ameliorate pathological changes associated with diabetic complications, including diabetic nephropathy, retinopathy, and neuropathy. In diabetic animal models, PKCβ inhibitor treatment has been shown to reduce albuminuria, glomerular hypertrophy, and mesangial expansion, indicating protection against diabetic kidney disease. In models of diabetic retinopathy, PKCβ inhibition reduces retinal vascular permeability and leukostasis. The compound has also shown efficacy in cancer models, where PKCβ inhibition suppresses tumor growth, angiogenesis, and metastasis. In cardiovascular models, PKCβ inhibition has demonstrated cardioprotective effects against ischemic injury and heart failure. The compound's in vivo efficacy supports the therapeutic potential of PKCβ inhibition in various diseases. However, the compound has not been approved for clinical use, and its in vivo pharmacokinetics and safety profile require further characterization. The compound is intended for research use only and is not for human therapeutic use.
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| Enzyme Assay |
PKCβ kinase activity assays are performed using recombinant human PKCβ1 or PKCβ2 enzymes. The enzyme is incubated with a peptide substrate (e.g., histone H1 or a specific PKC substrate peptide) and [γ-³²P]ATP in kinase buffer (50 mM HEPES pH 7.5, 10 mM MgCl₂, 1 mM CaCl₂, 100 µg/mL phosphatidylserine, 20 µg/mL diacylglycerol, 1 mM DTT). The reaction is incubated at 30°C for 15-30 minutes. Phosphorylated substrate is quantified by scintillation counting after spotting onto P81 phosphocellulose paper or by using a filter-binding assay. The PKCβ inhibitor is serially diluted in DMSO and added to the reaction mixture to determine IC50 values. The compound's selectivity is assessed by profiling against a panel of other PKC isozymes (PKCα, PKCγ, PKCε, etc.) and unrelated kinases. Each concentration is tested in duplicate, and IC50 values are calculated by non-linear regression analysis using appropriate software. Appropriate positive controls (e.g., staurosporine or other PKC inhibitors) and vehicle controls (DMSO) are included to validate the assay.
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| Cell Assay |
Cell Proliferation Assay[2]
Cell Types: 2F7, BCBL-1 cells Tested Concentrations: 0, 5, 10, 20, and 30 μM Incubation Duration: 48 hrs (hours) Experimental Results: A dose-dependent reduction in viability of the 2F7 and BCBL-1 cells starting at 5 μM and increasing with elevated inhibitor concentration. Apoptosis Analysis[2] Cell Types: 2F7 cells Tested Concentrations: 14 μM Incubation Duration: 2-48 hrs (hours) Experimental Results: Apoptotic induction in 2.1% of the 2F7 cells above background after 2 hrs (hours) of treatment, increasing through 48 hrs (hours) of treatment. Cell Cycle Analysis[2] Cell Types: BCBL -1 Cells Tested Concentrations: 15 μM (the IC50) Incubation Duration: 2-48 hrs (hours) Experimental Results: Inhibits cell cycle progression in 2F7 and BCBL-1 cells. Western Blot Analysis[2] Cell Types: BCBL-1 and 2F7 cell lines Tested Concentrations: 15 or 14 μM (at the IC50 respectively) Incubation Duration: 2-48 hrs (hours) Experimental Results: The expression of phospho-PKCβ in BCBL-1 and 2F7 cells decreased. Cellular PKCβ inhibition is evaluated in various cell lines, including those that express PKCβ such as endothelial cells, smooth muscle cells, or cancer cell lines. Cells are cultured in appropriate media (e.g., DMEM or RPMI-1640 with 10% FBS) at 37°C with 5% CO₂ and treated with the PKCβ inhibitor at concentrations ranging from 0.1 nM to 10 μM for 1-24 hours. PKCβ activity in cell lysates is assessed by measuring phosphorylation of specific PKCβ substrates (e.g., MARCKS, myristoylated alanine-rich C-kinase substrate) by Western blotting using phospho-specific antibodies. Downstream signaling pathways, including ERK, AKT, and NF-κB, are also assessed by Western blotting. Cell viability and proliferation are assessed using MTT, CCK-8, or CellTiter-Glo assays. Apoptosis is evaluated by Annexin V/PI staining, caspase-3/7 activity assays, and PARP cleavage Western blotting. Each experiment includes vehicle controls (DMSO) and appropriate positive controls (e.g., known PKC inhibitors like GF109203X or staurosporine) to validate the assay systems. |
| Animal Protocol |
In vivo efficacy of the PKCβ inhibitor is evaluated in various animal models, including models of diabetic complications, cancer, and cardiovascular diseases. The compound is administered orally or intraperitoneally at doses determined by preclinical studies. In diabetic models, animals (e.g., streptozotocin-induced diabetic rats or db/db mice) are treated with the compound for several weeks, and parameters such as blood glucose, albuminuria, retinal vascular permeability, and nerve conduction velocity are assessed. In cancer models, the compound is evaluated in mouse xenograft models using human cancer cell lines. Tumor growth is monitored by caliper measurements, and angiogenesis is assessed by immunohistochemistry for CD31 or other vascular markers. In cardiovascular models, the compound's effects on cardiac function, infarct size, and ischemic injury are evaluated. Body weight, clinical signs, and blood chemistry are monitored throughout the study to assess tolerability. At study endpoint, tissues are harvested for histopathological analysis and biochemical assays. Sample sizes typically range from 6-10 animals per group.
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| ADME/Pharmacokinetics |
Molecular Weight: 371.39. Formula: C21H17N5O2. CAS No.: 257879-35-9. Synonyms: PKCbeta Inhibitor; PKCβ Inhibitor; K00248; CHEMBL366266. IUPAC Name: 3-(1-(3-Imidazol-1-ylpropyl)-1H-indol-3-yl)-4-anilino-1H-pyrrole-2,5-dione. Appearance: Solid powder. Purity: Typically ≥90-98% (HPLC). Solubility: Soluble in DMSO. Storage: Powder at -20°C for up to 3 years; 4°C for up to 2 years; In solvent at -80°C for up to 6 months; -20°C for up to 1 month. Shipping: Room temperature or with ice pack. The compound is a potent, ATP-competitive, and selective PKCβ inhibitor with IC50s of 21 nM (PKCβ1) and 5 nM (PKCβ2). It is primarily used for phosphorylation and dephosphorylation research applications.
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| Toxicity/Toxicokinetics |
No comprehensive toxicology data are publicly available for the PKCβ inhibitor. The compound is intended for research use only and has not undergone full preclinical toxicology evaluation required for clinical development. As a kinase inhibitor, potential toxicities may include effects on normal cellular processes that depend on PKCβ signaling. The compound's selectivity for PKCβ over other PKC isozymes and unrelated kinases may reduce off-target toxicities. Standard toxicity studies would include acute toxicity assessment in rodents, repeated dose toxicity studies (14-day and 28-day), and genotoxicity screening (Ames test, micronucleus assay). The compound is for research use only and not for human therapeutic use.
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| References |
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| Additional Infomation |
3-Phenylino-4-[1-[3-(1-imidazolyl)propyl]-3-indolyl]pyrrole-2,5-dione is a member of the maleimide class of compounds.
The PKCβ inhibitor (CAS 257879-35-9) is also known as PKCbeta Inhibitor, PKCβ Inhibitor, K00248, and CHEMBL366266. Its IUPAC name is 3-(1-(3-Imidazol-1-ylpropyl)-1H-indol-3-yl)-4-anilino-1H-pyrrole-2,5-dione. The compound is an anilino-monoindolylmaleimide compound that is a potent inhibitor of PKCβ isozymes. It is a valuable tool for studying PKCβ-mediated signaling pathways in various biological contexts. PKCβ has been implicated in diabetic complications, cancer, and cardiovascular diseases, making this inhibitor a useful probe for target validation and drug discovery research. The compound is available from various chemical suppliers for research purposes. No clinical trials have been reported for this compound. The compound is strictly for research use only and not for human use. |
| Molecular Formula |
C24H21N5O2
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|---|---|
| Molecular Weight |
411.45584
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| Exact Mass |
411.17
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| CAS # |
257879-35-9
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| Related CAS # |
257879-35-9;
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| PubChem CID |
6419755
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| Appearance |
Yellow to orange solid powder
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| LogP |
3.756
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
4
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| Rotatable Bond Count |
7
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| Heavy Atom Count |
31
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| Complexity |
717
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| Defined Atom Stereocenter Count |
0
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| InChi Key |
KIWODJBCHRADND-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C24H21N5O2/c30-23-21(22(24(31)27-23)26-17-7-2-1-3-8-17)19-15-29(20-10-5-4-9-18(19)20)13-6-12-28-14-11-25-16-28/h1-5,7-11,14-16H,6,12-13H2,(H2,26,27,30,31)
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| Chemical Name |
3-anilino-4-[1-(3-imidazol-1-ylpropyl)indol-3-yl]pyrrole-2,5-dione
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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) |
DMSO : ~250 mg/mL (~607.59 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 6.25 mg/mL (15.19 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (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 62.5 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: ≥ 6.25 mg/mL (15.19 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (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 62.5 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.4304 mL | 12.1518 mL | 24.3037 mL | |
| 5 mM | 0.4861 mL | 2.4304 mL | 4.8607 mL | |
| 10 mM | 0.2430 mL | 1.2152 mL | 2.4304 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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