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| Targets |
Protein kinase C delta (PKCdelta), a member of the novel PKC subfamily involved in cell proliferation, differentiation, and apoptosis. BJE6-106 is a potent and selective PKCdelta inhibitor with an IC50 of 0.05 microM and targets selectivity over classical PKC isozyme PKCalpha (IC50 = 50 microM), representing a 1000-fold selectivity. By inhibiting PKCdelta, the compound induces caspase-dependent apoptosis and activates the MKK4-JNK-H2AX signaling pathway.
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| ln Vitro |
BJE6-106 (B106) (0.2 μM, 0.5 μM; 24-72 hours) reduces cell survival in melanoma cell lines carrying NRAS mutations [1]. BJE6-106 (B106) (0.2 μM, 0.5 μM; 6-24 hours) causes caspase-dependent apoptosis and enhances caspase 3/7 activity. The effect of B106 is stronger than that of Rottlerin (10-fold) in SBcl2 cells [1]. BJE6-106 (B106) (0.5 μM; 2-10 hours) triggers the MKK4-JNK-H2AX pathway by triggering MKK4, JNK and H2AX activation at separate periods in SBcl2 cells [1].
In vitro, BJE6-106 (0.2 microM, 0.5 microM; 24-72 hours) suppresses cell survival in melanoma cell lines with NRAS mutations including SBe12, FM6, SKMEL2, WM1366, WM1361A, and WM852. The compound (0.2 microM, 0.5 microM; 6-24 hours) triggers caspase-dependent apoptosis and increases caspase 3/7 activity. The effect of B106 is 10-fold greater than rottlerin in SBe12 cells. BJE6-106 (0.5 microM; 2-10 hours) activates the MKK4-JNK-H2AX pathway by inducing MKK4, JNK, and H2AX activation at different times in SBe12 cells. |
| ln Vivo |
In vivo studies of BJE6-106 have demonstrated anti-tumor effects including inhibition of growth and metastasis in preclinical studies. The compound has tumor-specific effects and has been investigated for its therapeutic potential in cancers where PKC dysregulation plays a significant role. BJE6-106 induces apoptosis by inhibiting growth factor signaling pathways required for cell proliferation. Ongoing research aims to evaluate BJE6-106 as a therapeutic option for cancer, focusing on NRAS-mutant melanoma and other PKCdelta-dependent malignancies.
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| Enzyme Assay |
In vitro PKCdelta kinase inhibition assays for BJE6-106 measure inhibition of PKCdelta enzymatic activity. The assay uses recombinant human PKCdelta enzyme and a peptide substrate (e.g., histone H1 or a specific PKC substrate peptide) in the presence of ATP and phospholipid cofactors (phosphatidylserine, diacylglycerol). The compound is serially diluted in assay buffer and pre-incubated with the enzyme for 15-30 minutes. The reaction is initiated by adding ATP and substrate, and after incubation at 30degC, phosphorylation is detected using radiometric (33P-ATP), fluorescence, or luminescence-based methods. IC50 values are calculated from dose-response curves.
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| Cell Assay |
Cell Viability Assay[1]
Cell Types: Melanoma cell lines with NRAS mutations: SBcl2, FM6, SKMEL2, WM1366, WM1361A, and WM852 Cell Tested Concentrations: 0.2 μM, 0.5 μM Incubation Duration: 24 hrs (hours), 48 hrs (hours), or 72 hrs (hours) Experimental Results: Inhibition of cell survival in melanoma cell lines. Apoptosis analysis[1] Cell Types: SBcl2 Cell Tested Concentrations: 0.2 μM, 0.5 μM Incubation Duration: 6 hrs (hours), 12 hrs (hours) or 24 hrs (hours) Experimental Results: Induction of caspase 3/7 activation. Western Blot Analysis[1] Cell Types: SBcl2 Cell Tested Concentrations: 0.2 μM, 0.5 μM Incubation Duration: 2 hrs (hours), 5 hrs (hours), 10 hrs (hours) Experimental Results: Increased phosphorylation of MKK4, JNK and H2AX. In vitro cell-based assays for BJE6-106 use melanoma cell lines with NRAS mutations including SBe12, FM6, SKMEL2, WM1366, WM1361A, and WM852. Cells are cultured in appropriate media and treated with BJE6-106 at concentrations of 0.2 microM and 0.5 microM for 24-72 hours. Cell viability is measured using MTT or CellTiter-Glo assays. Apoptosis is evaluated using Annexin V/PI staining or caspase-3/7 activity assays. MKK4, JNK, and H2AX activation is assessed by Western blotting using phospho-specific antibodies at various time points (2-10 hours). |
| Animal Protocol |
In vivo animal studies for BJE6-106 are conducted in murine xenograft models of melanoma and other cancers. Immunodeficient mice are implanted subcutaneously with NRAS-mutant melanoma cells. When tumors reach a certain size, animals are randomized to receive vehicle control or BJE6-106 at various doses via intraperitoneal or oral administration. Tumor volumes are measured with calipers every 2-3 days, and tumor growth inhibition and metastasis suppression are evaluated. Tumor tissues are collected for histology and biomarker analysis including apoptosis markers and PKCdelta signaling pathway components.
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| ADME/Pharmacokinetics |
Pharmacokinetic properties of BJE6-106 are characteristic of small-molecule kinase inhibitors. With a molecular weight of 381.47 and a molecular formula of C26H23NO2, the compound is soluble in DMSO at 50 mg/mL. It is stored as a powder at -20degC for up to 3 years or in solution at -80degC for up to 6 months. In vivo formulations typically use 10% DMSO + 90% (20% SBE-beta-CD in saline) or 10% DMSO + 90% corn oil. Standard pharmacokinetic parameters can be determined in preclinical species.
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| Toxicity/Toxicokinetics |
BJE6-106 is intended for research use only and is not for human therapeutic use. Standard safety precautions for handling chemical compounds apply. The compound is not approved for clinical use. Preclinical toxicity studies are ongoing to evaluate its safety profile.
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| References | |
| Additional Infomation |
BJE6-106 is a research-grade potent and selective third-generation PKCdelta inhibitor. It has an IC50 of 0.05 microM for PKCdelta and exhibits 1000-fold selectivity over PKCalpha (IC50 = 50 microM). The compound induces caspase-dependent apoptosis and activates the MKK4-JNK-H2AX pathway. It has tumor-specific effects and is used for researching NRAS-mutant melanoma. Purity is typically ≥99%. Not approved for clinical use.
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| Molecular Formula |
C26H23NO2
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| Molecular Weight |
381.4663
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| Exact Mass |
381.172
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| CAS # |
1564249-38-2
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| PubChem CID |
85471521
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| Appearance |
White to off-white solid powder
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| LogP |
5.6
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| Hydrogen Bond Donor Count |
0
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| Hydrogen Bond Acceptor Count |
2
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| Rotatable Bond Count |
4
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| Heavy Atom Count |
29
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| Complexity |
606
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| Defined Atom Stereocenter Count |
0
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| SMILES |
O1C2C(C([H])=O)=C([H])C(=C([H])C=2C([H])=C([H])C1(C([H])([H])[H])C([H])([H])[H])C([H])([H])C([H])([H])N1C2=C([H])C([H])=C([H])C([H])=C2C2=C([H])C([H])=C([H])C([H])=C12
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| InChi Key |
QLDDENZBVHBRKN-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C26H23NO2/c1-26(2)13-11-19-15-18(16-20(17-28)25(19)29-26)12-14-27-23-9-5-3-7-21(23)22-8-4-6-10-24(22)27/h3-11,13,15-17H,12,14H2,1-2H3
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| Chemical Name |
6-(2-carbazol-9-ylethyl)-2,2-dimethylchromene-8-carbaldehyde
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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 : ~50 mg/mL (~131.07 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: 2.5 mg/mL (6.55 mM) in 10% DMSO + 90% (20% SBE-β-CD in 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 25.0 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. Solubility in Formulation 2: ≥ 2.5 mg/mL (6.55 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 25.0 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 | 2.6214 mL | 13.1072 mL | 26.2144 mL | |
| 5 mM | 0.5243 mL | 2.6214 mL | 5.2429 mL | |
| 10 mM | 0.2621 mL | 1.3107 mL | 2.6214 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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