| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 50mg |
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| 100mg |
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| Other Sizes |
| Targets |
MKK4 (IC₅₀ = 4 nM);
MKK7 (IC₅₀ = 181 nM)[1]
The primary targets of BSJ-04-122 are MKK4 (MAP kinase kinase 4, also known as MEK4) and MKK7 (MAP kinase kinase 7, also known as MEK7). These are dual-specificity kinases that function as upstream activators of the JNK (c-Jun N-terminal kinase) signaling pathway. MKK4 and MKK7 phosphorylate JNK at threonine and tyrosine residues, leading to JNK activation. BSJ-04-122 is a covalent inhibitor, meaning it forms an irreversible bond with its targets, resulting in sustained inhibition. By inhibiting both MKK4 and MKK7, BSJ-04-122 effectively blocks JNK activation. |
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| ln Vitro |
MKK4 and MKK7 are inhibited by BSJ-04-122, with IC50 values of 4 nM and 181 nM, respectively[1]. JNK phosphorylation is significantly reduced by BSJ-04-122 (1, 5, 10 μM; 6 h) [1]. When coupled with JNK-IN-8, BSJ-04-122 (0, 1.25, 2.5, 5, 10, 20 μM; 72 h) demonstrated increased antiproliferative effects [1].
Kinase activity inhibition: BSJ-04-122 covalently binds to the Cys247 residue of MKK4, dose-dependently inhibiting MKK4 and MKK7 kinase activities (IC₅₀: 4 nM for MKK4, 181 nM for MKK7). It directly blocks JNK phosphorylation by suppressing MKK4/7-mediated activation [1] Antiproliferative activity: In MDA-MB-231 triple-negative breast cancer cells, BSJ-04-122 (1-100 μM) exhibits concentration-dependent antiproliferative effects after 72-hour treatment. Its inhibitory effect is significantly enhanced when combined with JNK-IN-8, indicating a synergistic mechanism [1] Signal pathway regulation: Western blot analysis shows that BSJ-04-122 (1-10 μM) reduces the phosphorylation level of JNK at T183/Y185 in MDA-MB-231 cells after 6-hour treatment, confirming inhibition of the MKK4/7-JNK pathway [1] BSJ-04-122 inhibits MKK4 and MKK7 with IC50 values of 4 nM and 181 nM, respectively. At concentrations of 1, 5, and 10 μM for 6 hours, it significantly reduces the phosphorylation level of JNK, confirming its ability to inhibit the MKK4/7-JNK signaling axis. When combined with JNK-IN-8, BSJ-04-122 demonstrates enhanced anti-proliferative effects in cancer cells, suggesting a synergistic effect of dual MKK4/7 and JNK inhibition. The compound is supplied as a solid with a purity of 98.09% and is soluble in DMSO at 55.5 mg/mL (176.9 mM). |
| ln Vivo |
In vivo, BSJ-04-122 is used in cancer research to study the role of the MKK4/7-JNK signaling pathway in tumor growth and progression. By covalently inhibiting MKK4 and MKK7, the compound blocks JNK activation and may reduce tumor cell proliferation and survival. Its efficacy would be assessed in animal models of cancer, with endpoints including tumor growth inhibition, analysis of JNK pathway signaling, and evaluation of anti-proliferative effects. The compound's covalent mechanism of action provides sustained target inhibition.
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| Enzyme Assay |
MKK4/7 kinase activity assay: Recombinant MKK4 or MKK7 proteins are incubated with ATP and substrates (JNK or p38 MAPK) in reaction buffer, followed by addition of BSJ-04-122 at different concentrations (0.1-1000 nM). Substrate phosphorylation levels are detected (via radiolabeling or fluorescence labeling) to evaluate inhibitory effects. Results show BSJ-04-122 has significantly higher inhibitory activity against MKK4 than MKK7 [1].
In vitro enzyme activity assays for BSJ-04-122 typically involve measuring its ability to inhibit MKK4 and MKK7 kinase activity. Recombinant MKK4 and MKK7 enzymes are incubated with their substrate (JNK) in the presence of ATP and increasing concentrations of BSJ-04-122. Kinase activity is measured by detecting phosphorylation of JNK, and the IC50 values are determined from the dose-response curves. The reported IC50 values are 4 nM for MKK4 and 181 nM for MKK7. The covalent nature of the inhibition can be confirmed by pre-incubation and washout experiments. |
| Cell Assay |
Western Blot Analysis[1]
Cell Types: MDA-MB-231 cells Tested Concentrations: 1, 5, 10 μM Incubation Duration: 6 h Experimental Results: Dramatically diminished levels of T183/Y185 pJNK at 5 μM. Cell Proliferation Assay[1] Cell Types: MDA-MB-231 cells Tested Concentrations: 1-100 μM; 0, 1.25, 2.5, 5, 10, 20 μM Incubation Duration: 72 h Experimental Results: demonstrated antiproliferative effects when combined with JNK-IN-8 in MDA-MB-231 cells. Cell proliferation assay: MDA-MB-231 cells are seeded in 96-well plates and treated with BSJ-04-122 (0-100 μM) alone or in combination with JNK-IN-8. After 72-hour incubation, cell viability is measured by MTT assay. Both single-agent and combined treatments significantly reduce cell viability, with the combination showing stronger effects [1] Apoptosis detection: Annexin V-FITC/PI double staining assay reveals that BSJ-04-122 (5-20 μM) increases the proportion of early apoptotic cells in MDA-MB-231 cells after 48-hour treatment, accompanied by elevated Caspase-3/7 activity, indicating an apoptosis-inducing mechanism [1] Cellular assays for BSJ-04-122 involve treating cancer cell lines with the compound and measuring its effects on JNK phosphorylation and cell proliferation. At 1, 5, and 10 μM for 6 hours, BSJ-04-122 significantly reduces JNK phosphorylation levels. When combined with JNK-IN-8 at concentrations of 0, 1.25, 2.5, 5, 10, and 20 μM for 72 hours, BSJ-04-122 exhibits enhanced anti-proliferative effects. Cell viability is assessed using standard assays such as MTT or CellTiter-Glo. |
| Animal Protocol |
In vivo efficacy of BSJ-04-122 would be evaluated in mouse xenograft models of cancer. The compound could be administered orally or via injection, depending on its pharmacokinetic properties. Efficacy endpoints would include tumor growth inhibition, analysis of JNK pathway signaling in tumor tissue, and evaluation of anti-proliferative and pro-apoptotic effects. Its covalent mechanism of action provides sustained target inhibition, which may translate to durable antitumor activity.
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| ADME/Pharmacokinetics |
BSJ-04-122 has a molecular weight of 313.74 and a molecular formula of C15H12ClN5O. It is a covalent MKK4/7 dual inhibitor. The compound is supplied as a solid with a purity of 98.09% and is soluble in DMSO at 55.5 mg/mL (176.9 mM). For in vivo studies, it can be formulated in 10% DMSO + 40% PEG300 + 5% Tween 80 + 45% Saline at 5 mg/mL. The compound should be stored as a powder at -20°C for up to 3 years and in solvent at -80°C for up to 1 year.
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| Toxicity/Toxicokinetics |
No specific toxicity data is available for BSJ-04-122 in the provided literature. As a research compound, its safety profile would be an important consideration for in vivo applications. Potential toxicities could be related to its effects on the JNK signaling pathway, which plays roles in various cellular processes including stress responses, apoptosis, and inflammation. Standard preclinical safety studies would be required to evaluate its safety for potential therapeutic applications. The compound is for research use only and is not intended for human therapeutic use.
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| References | |
| Additional Infomation |
Mechanism of action: BSJ-04-122 irreversibly inhibits the MKK4/7-JNK/p38 MAPK signaling pathway by covalently binding to Cys247 residues of MKK4, thereby blocking tumor cell proliferation and inducing apoptosis [1]. Potential indications: In vitro experiments showed that BSJ-04-122 has significant inhibitory activity against malignant tumor cells such as triple-negative breast cancer and glioma, indicating its potential application value in anticancer treatment [1]. Innovation: As the first reported covalent dual inhibitor of MKK4/7, BSJ-04-122 provides a new chemical framework and mechanism of action for the development of anticancer drugs targeting the MAPK pathway [1].
BSJ-04-122 is a covalent dual inhibitor of MKK4 and MKK7, with IC50 values of 4 nM and 181 nM, respectively. It has a molecular formula of C15H12ClN5O and a molecular weight of 313.74. At concentrations of 1, 5, and 10 μM for 6 hours, BSJ-04-122 significantly reduces JNK phosphorylation. When combined with JNK-IN-8, it exhibits enhanced anti-proliferative effects in cancer cells. BSJ-04-122 is used in cancer research. Its covalent mechanism of action provides sustained inhibition of the MKK4/7-JNK signaling pathway. |
| Molecular Formula |
C15H12CLN5O
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|---|---|
| Molecular Weight |
313.741681098938
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| Exact Mass |
313.073
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| CAS # |
2513289-74-0
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| PubChem CID |
166642484
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| Appearance |
White to off-white solid powder
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| LogP |
2.9
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
4
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| Rotatable Bond Count |
4
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| Heavy Atom Count |
22
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| Complexity |
421
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| Defined Atom Stereocenter Count |
0
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| SMILES |
ClC1=CNC2C1=C(N=CN=2)NC1C=CC=CC=1NC(C=C)=O
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| InChi Key |
LWXOPXNDPRPGMJ-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C15H12ClN5O/c1-2-12(22)20-10-5-3-4-6-11(10)21-15-13-9(16)7-17-14(13)18-8-19-15/h2-8H,1H2,(H,20,22)(H2,17,18,19,21)
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| Chemical Name |
N-[2-[(5-chloro-7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino]phenyl]prop-2-enamide
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| Synonyms |
BSJ-04-122; 2513289-74-0; SCHEMBL27051832; N-(2-((5-Chloro-7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino)phenyl)acrylamide
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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: 100 mg/mL (318.74 mM)
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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 | 3.1874 mL | 15.9368 mL | 31.8735 mL | |
| 5 mM | 0.6375 mL | 3.1874 mL | 6.3747 mL | |
| 10 mM | 0.3187 mL | 1.5937 mL | 3.1874 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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