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| 5mg |
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| Targets |
BRD7389 targets the RSK (ribosomal S6 kinase) family kinases, specifically RSK1, RSK2, and RSK3. RSK kinases are downstream effectors of the ERK/MAPK signaling pathway, playing important roles in cell proliferation, survival, and differentiation. BRD7389 inhibits RSK1 with an IC50 of 1.5 μM, RSK2 with an IC50 of 2.4 μM, and RSK3 with an IC50 of 1.2 μM. By inhibiting RSK kinases, the compound modulates downstream signaling pathways involved in insulin expression and cell proliferation. The compound shows specificity for RSK family kinases over other kinases.
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| ln Vitro |
After three days of treatment, BRD7389 (0.425-6.8 μM) increases insulin expression in mouse alpha cells. Insulin (Ins2) mRNA is dose-dependently upregulated by BRD7389, reaching a peak value of 0.85 μM; insulin gene expression can be more effectively induced by BRD7389 administration for five days, increasing by around 50-fold at a concentration of 0.85 μM [1]. In mouse alpha cell lines, BRD7389 (0.85–6.8μM) dramatically increases Pdx1 mRNA expression [1]. In primary human islet cells, BRD7389 also upregulates the expression of genes unique to beta cells [1]. While BRD7389 (1 μM) had little influence on basal levels of proliferation, it entirely eliminated carbachol-stimulated cell proliferation when administered 30 minutes before carbachol treatment for 48 hours [2].
In vitro studies demonstrate that BRD7389 is a specific RSK family kinase inhibitor. The compound inhibits RSK1, RSK2, and RSK3 with IC50 values of 1.5 μM, 2.4 μM, and 1.2 μM, respectively. BRD7389 induces insulin expression in pancreatic α-cells. In human primary islet cultures, BRD7389 treatments result in a decrease of overall cell counts over time due to apoptosis induction, while insulin-positive cell population remains more or less unaffected. The compound increases the endocrine cell content and function of donor human pancreatic islets in culture. In SNU-407 colon cancer cells, BRD7389 blocks muscarinic acetylcholine receptor-stimulated RSK activation and subsequent proliferation. |
| ln Vivo |
In vivo data for BRD7389 is limited in the available literature. Based on its mechanism as an RSK family kinase inhibitor that induces insulin expression, the compound may have potential for studying diabetes and islet cell biology. The compound's effects on pancreatic islet function suggest potential for investigating beta-cell regeneration and diabetes. Further in vivo studies in animal models of diabetes and cancer are warranted.
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| Enzyme Assay |
The in vitro kinase assay for BRD7389 involves measuring RSK kinase activity using recombinant RSK1, RSK2, or RSK3 and a peptide substrate. Kinase, substrate, and varying concentrations of BRD7389 (0.1-100 μM) are incubated with ATP for 30-60 minutes. Phosphorylated substrate is detected using scintillation proximity assay, ELISA, or mobility shift assay. IC50 values are calculated from dose-response curves. Selectivity is assessed by testing against a panel of kinases. Cell-based assays measure RSK phosphorylation of downstream targets (e.g., CREB) by Western blot or ELISA in cells treated with BRD7389.
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| Cell Assay |
RT-PCR[1]
Cell Types: Mouse alpha cell line Tested Concentrations: 0.425, 0.85, 1.7, 3.4, 6.8 μM Incubation Duration: 3 days and 5 days Experimental Results: Pdx1 expression was up-regulated. Cell proliferation assay [2] Cell Types: SNU-407 colon cancer cells Tested Concentrations: 1 μM Incubation Duration: Added 30 minutes before carbachol treatment (48 hrs (hours)) Experimental Results: Almost complete blockade of carbachol (1 mM) stimulated Cell Proliferation. In vitro cellular assays for BRD7389 typically use pancreatic α-cells or islet cultures, as well as cancer cell lines. Cells are cultured in appropriate media and treated with the compound at concentrations of 0.1-100 μM for 1-7 days. Insulin expression is measured by ELISA, immunofluorescence, or qPCR. Endocrine cell content and function are assessed by hormone secretion assays. Cell proliferation is assessed by BrdU incorporation or cell counting. Cell viability is assessed using MTT or CCK-8 assays. RSK activation is assessed by Western blot of phosphorylated RSK and downstream targets. Apoptosis is evaluated using caspase-3/7 activity assays. |
| Animal Protocol |
In vivo animal studies for BRD7389 would typically involve mouse models of diabetes or cancer. Diabetic mice are treated with the compound via oral gavage or intraperitoneal injection at doses of 1-50 mg/kg daily for 2-4 weeks. Blood glucose and insulin levels are measured. Pancreatic islet function is assessed by glucose tolerance tests and insulin secretion assays. Pancreatic histology is performed to evaluate islet cell composition. For cancer studies, tumor-bearing mice are treated with the compound and tumor growth is monitored. RSK inhibition in tissues is confirmed by Western blot.
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| ADME/Pharmacokinetics |
Pharmacokinetic properties of BRD7389 are not extensively reported. The compound has a molecular weight of 366.42 and molecular formula of C24H18N2O2. It is soluble in DMSO and other organic solvents. The compound should be stored at -80°C for long-term preservation and at -20°C for short-term storage. Based on its physicochemical properties, the compound is expected to have reasonable membrane permeability. Further studies on oral bioavailability, plasma half-life, and tissue distribution are needed.
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| Toxicity/Toxicokinetics |
Toxicological data for BRD7389 is not extensively reported. As an RSK inhibitor that induces apoptosis in some cell types, the compound may have cytotoxic effects. The compound is for research use only and not for human therapeutic applications. Standard safety precautions should be followed when handling. For detailed toxicity information, specialized toxicological studies would need to be performed.
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| References |
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| Additional Infomation |
LSM-4550 belongs to the anthracene class of compounds.
BRD7389 is a research-grade compound with CAS number 376382-11-5. Its molecular formula is C24H18N2O2 and molecular weight is 366.42. The compound is a specific RSK family kinase inhibitor with IC50 values of 1.5 μM (RSK1), 2.4 μM (RSK2), and 1.2 μM (RSK3). It induces insulin expression in pancreatic α-cells and increases endocrine cell content and function of human pancreatic islets. It blocks RSK activation and proliferation in colon cancer cells. This compound has not advanced to clinical trials and is not FDA-approved. It is strictly for research purposes only. |
| Molecular Formula |
C24H18N2O2
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| Molecular Weight |
366.42
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| Exact Mass |
366.137
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| CAS # |
376382-11-5
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| PubChem CID |
1080352
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| Appearance |
Light yellow to yellow solid powder
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| LogP |
4.879
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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 |
4
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| Heavy Atom Count |
28
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| Complexity |
664
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| Defined Atom Stereocenter Count |
0
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| InChi Key |
XASCINRGTHLHGM-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C24H18N2O2/c27-23-17-10-5-4-9-16(17)21-20-18(23)11-6-12-19(20)26-24(28)22(21)25-14-13-15-7-2-1-3-8-15/h1-12,25H,13-14H2,(H,26,28)
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| Chemical Name |
16-(2-phenylethylamino)-14-azatetracyclo[7.7.1.02,7.013,17]heptadeca-1(16),2,4,6,9(17),10,12-heptaene-8,15-dione
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| Synonyms |
BRD 7389; BRD-7389; BRD7389
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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 Note: This product requires protection from light (avoid light exposure) during transportation and storage. |
| 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 : ~20.83 mg/mL (~56.85 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 | 2.7291 mL | 13.6455 mL | 27.2911 mL | |
| 5 mM | 0.5458 mL | 2.7291 mL | 5.4582 mL | |
| 10 mM | 0.2729 mL | 1.3646 mL | 2.7291 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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