| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| Targets |
Bim
The molecular target of Bim-IN-1 is the cellular machinery that regulates Bim expression. Bim is a pro-apoptotic protein that is tightly regulated at transcriptional and post-translational levels. In many cancer cells, Bim expression is suppressed, allowing evasion of apoptosis. Bim-IN-1, as an inhibitor of Bim expression, likely reduces transcription of the Bim gene or increases its degradation. The exact mechanism and direct protein target are not fully defined. However, the compound has minimal effect on PKA activity, suggesting it does not act through this major signaling pathway. By reducing Bim expression, the compound makes cells more resistant to apoptosis. |
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| ln Vitro |
Compound 63, which is Bim-IN-1 (mouse embryonic fibroblasts; 0, 25, 50 μM; 72 hours) exhibits a significant decrease in Bim expression levels at a low micromolar level while maintaining minimal toxicity.
In vitro, Bim-IN-1 is a potent inhibitor of Bim expression. In cell-based assays using mouse embryonic fibroblasts (MEFs), treatment with Bim-IN-1 at 25 and 50 uM for 72 hours resulted in a strong reduction of Bim expression levels at a low micromolar level with low toxicity. This indicates that the compound can effectively suppress Bim protein levels without causing significant cell death. The reduction in Bim expression correlates with a decrease in the cell's propensity to undergo apoptosis. The compound shows little to no inhibitory effect on PKA activity, demonstrating selectivity. The exact IC₅0 for reduction of Bim expression is not specified but is in the low micromolar range. |
| ln Vivo |
In vivo studies for Bim-IN-1 have not been reported in the public literature. The compound is primarily a research tool for in vitro experiments. Based on its ability to reduce Bim expression, it is hypothesized that systemic administration could inhibit apoptosis in various tissues, potentially protecting them from damage. For example, it might be tested in mouse models of acute kidney injury (AKI) or myocardial infarction (MI) to see if it can reduce cell death and improve outcomes. Conversely, in cancer, an inhibitor of Bim would promote tumor cell survival and would be counterproductive. Its in vivo applications are more likely in the context of protecting healthy tissues, but no such studies have been published.
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| Enzyme Assay |
A typical non-cellular binding assay for Bim-IN-1 is not standard, as its primary activity is on cellular gene expression. To assess its effect on the Bim promoter, a luciferase reporter assay can be developed. A plasmid containing the Bim promoter region fused to a luciferase reporter gene is transfected into HEK293 cells. After 24 h, cells are treated with Bim-IN-1 (0.1-50 uM) for 24 h. Luciferase activity is measured. A reduction indicates inhibition of Bim promoter activity. Since the compound has little effect on PKA, a purified PKA enzyme activity assay can be used as a counter-screen. A PKA activity assay kit is used according to the manufacturer's protocol, with Bim-IN-1 tested up to 100 uM.
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| Cell Assay |
A standard in vitro cell-based assay uses primary or immortalized mouse embryonic fibroblasts (MEFs). MEFs are cultured in DMEM with 10% FBS at 37degC, 5% CO2. For Bim expression assay, MEFs are seeded in 6-well plates at 3 × 10⁵ cells/well. After 24 h, cells are treated with Bim-IN-1 at 0, 12.5, 25, and 50 uM for 72 h. Cells are lysed in RIPA buffer. Protein concentration is determined by BCA. Equal protein (30 ug) is separated by SDS-PAGE, transferred to PVDF, and immunoblotted with anti-Bim antibody and GAPDH as loading control. Bands are visualized by ECL and quantified by densitometry. For viability, MEFs are seeded in 96-well plates at 1 × 10⁴ cells/well and treated similarly, then viability measured by MTT assay.
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| Animal Protocol |
An in vivo animal study for Bim-IN-1 would likely be performed in a mouse model of acute kidney injury (AKI). Adult male C57BL/6 mice (8-10 weeks) are used. AKI is induced by intraperitoneal (IP) injection of folic acid (250 mg/kg) or by ischemia-reperfusion (IR) injury (clamping renal pedicles for 30-45 min). Bim-IN-1 is formulated in a vehicle (e.g., 10% DMSO, 40% PEG300, 5% Tween-80, 45% saline) and administered IP at 5, 10, and 20 mg/kg 1 h before AKI induction and then once daily for 3 days. Control receives vehicle. Blood is collected at 24, 48, 72 h for serum creatinine and BUN. Kidneys are harvested at 72 h for H&E staining and TUNEL assay. Bim expression in kidney is measured by Western blot. All procedures require IACUC approval.
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| ADME/Pharmacokinetics |
The pharmacokinetic (PK) properties of Bim-IN-1 have not been reported. As a small molecule with molecular weight 416.34 g/mol, it has drug-like properties. It is soluble in DMSO at 200 mg/mL. In vivo formulations can be prepared using DMSO, PEG300, Tween-80, and saline, indicating lipophilic character and good membrane permeability. No specific PK parameters (absorption, distribution, half-life) are available. Based on the need for daily dosing in a hypothetical study, the compound may have a moderate half-life. Human PK data is not available. For research use only.
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| Toxicity/Toxicokinetics |
Toxicological data for Bim-IN-1 is limited. In published in vitro studies using MEFs, the compound was described as having minimal toxicity at concentrations up to 50 uM for 72 h, with no significant cell death. This suggests a good safety margin in cell culture. However, a full toxicological evaluation in animals has not been performed. Off-target effects beyond PKA have not been explored. Standard safety precautions (gloves, lab coat, eye protection) should be used. For research use only; not for human therapeutic administration.
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| References | |
| Additional Infomation |
Bim-IN-1 is not an approved drug and has no clinical development history. It is a research tool used to study the role of the pro-apoptotic protein Bim in various biological processes, including cancer, immunology, and neurodegeneration. Its unique mechanism of action-reducing the expression of Bim without affecting PKA activity-makes it a valuable tool for dissecting pathways that regulate Bim. It can be used to investigate how cells become resistant to apoptosis and to explore therapeutic strategies that aim to induce cell death by upregulating Bim. No clinical trials have been registered for this compound. For research use only.
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| Molecular Formula |
C19H20CL2FNO2S
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| Molecular Weight |
416.337005615234
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| Exact Mass |
415.058
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| CAS # |
2909483-36-7
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| PubChem CID |
163196209
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| Appearance |
White to light yellow solid powder
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| Hydrogen Bond Donor Count |
0
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| Hydrogen Bond Acceptor Count |
4
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| Rotatable Bond Count |
4
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| Heavy Atom Count |
26
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| Complexity |
556
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| Defined Atom Stereocenter Count |
0
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| SMILES |
O=S(CC1C(Cl)=CC(Cl)=CC=1)(N1C(C2C=C(F)C=CC=2)CCCCC1)=O
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| InChi Key |
SFVNBTZMJWQDLM-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C19H20Cl2FNO2S/c20-16-9-8-15(18(21)12-16)13-26(24,25)23-10-3-1-2-7-19(23)14-5-4-6-17(22)11-14/h4-6,8-9,11-12,19H,1-3,7,10,13H2
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| Chemical Name |
1-[(2,4-dichlorophenyl)methylsulfonyl]-2-(3-fluorophenyl)azepane
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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: 200 mg/mL (480.38 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 | 2.4019 mL | 12.0094 mL | 24.0188 mL | |
| 5 mM | 0.4804 mL | 2.4019 mL | 4.8038 mL | |
| 10 mM | 0.2402 mL | 1.2009 mL | 2.4019 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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