| Size | Price | Stock | Qty |
|---|---|---|---|
| 5mg |
|
||
| 10mg |
|
||
| 50mg | |||
| 100mg | |||
| Other Sizes |
| Targets |
MCL-1 and BCL-2. The compound is a BH3-mimetic, meaning it binds to the hydrophobic groove of these anti-apoptotic proteins, blocking their ability to bind and neutralize pro-apoptotic effectors like BAX and BAK.
|
|---|---|
| ln Vitro |
In in vitro biochemical assays, MCL-1/BCL-2-IN-3 demonstrates potent inhibitory activity. It has an IC₅0 value of 5.95 microM against MCL-1 and an IC₅0 value of 4.78 microM against BCL-2. These values indicate it is a dual inhibitor with slightly higher potency against MCL-1 in this setting. This dual inhibition strategy is important for overcoming resistance, as cancers often upregulate one or both proteins to survive.
|
| ln Vivo |
Specific in vivo activity data for this compound is not provided in the search results. However, as a dual inhibitor of MCL-1 and BCL-2, it is designed to induce robust apoptosis in cancer cells. Researchers could use this compound in mouse xenograft models of B-cell malignancies (e.g., lymphoma or leukemia) where both BCL-2 and MCL-1 are expressed. It would be tested for its ability to reduce tumor growth and regress tumors.
|
| Enzyme Assay |
A non-cellular binding assay is used to determine the IC₅0 values. A typical method is a fluorescence polarization (FP) assay. A fluorescently-labeled BIM BH3 peptide is incubated with either purified MCL-1 or BCL-2 protein. The binding of the BH3 peptide to the protein causes a change in fluorescence polarization. Varying concentrations of MCL-1/BCL-2-IN-3 are added. The compound competes with the BH3 peptide for binding to the protein, leading to a decrease in fluorescence polarization. The IC₅0 is calculated from the displacement curve.
|
| Cell Assay |
An in vitro cell-based assay is used to measure the functional consequence of target inhibition: apoptosis. Cancer cell lines known to depend on BCL-2 and/or MCL-1 for survival (e.g., H929 multiple myeloma cells) are treated with a range of concentrations of MCL-1/BCL-2-IN-3 for 24-48 hours. Apoptosis is then quantified using a standard assay such as an Annexin V-FITC/PI double staining protocol analyzed by flow cytometry. The IC₅0 for inducing cell death can be calculated.
|
| Animal Protocol |
Specific in vivo protocols are not provided. A standard efficacy study for an oncology compound involves using a subcutaneous xenograft mouse model. For example, NOD/SCID mice are injected with a B-cell lymphoma cell line (e.g., DOHH2). When tumors reach a measurable size (e.g., 150 mm3), the compound is typically administered daily via intraperitoneal (IP) injection. Tumor volume is measured with calipers every few days. At the end of the study, tumors are excised and lysed for analysis of cleaved PARP or caspase-3 by Western blot to confirm pharmacodynamic activity.
|
| ADME/Pharmacokinetics |
Specific PK data for this compound is not provided. As a standard research compound for hit-to-lead optimization, its PK properties such as oral bioavailability, plasma half-life, and clearance would be evaluated in rodents to assess its suitability for in vivo efficacy studies.
|
| Toxicity/Toxicokinetics |
No specific toxicity data is available. Inhibition of BCL-2 can cause on-target toxicities, such as thrombocytopenia (low platelet count), as platelets require BCL-xL for survival. MCL-1 inhibitors may cause cardiotoxicity. A key goal of developing dual inhibitors is to find a molecule with an acceptable therapeutic window.
|
| References |
[1]. Wang Z, et al. Proteolysis Targeting Chimeras for the Selective Degradation of Mcl-1/Bcl-2 Derived from Nonselective Target Binding Ligands. J Med Chem. 2019 Sep 12;62(17):8152-8163.
|
| Additional Infomation |
Targeting apoptosis is a clinically validated strategy, as demonstrated by the BCL-2 selective inhibitor venetoclax (ABT-199). However, resistance to venetoclax is often mediated by upregulation of MCL-1. MCL-1/BCL-2-IN-3 is a dual inhibitor designed to overcome this resistance. The compound is a valuable tool for cancer research but has not been approved for clinical use. The "IN-3" designation indicates it is a third-generation inhibitor in a discovery series.
|
| Molecular Formula |
C27H25BRN2O5S
|
|---|---|
| Molecular Weight |
569.46680521965
|
| Exact Mass |
568.066
|
| CAS # |
2163793-55-1
|
| PubChem CID |
145712377
|
| Appearance |
Light yellow to yellow solid powder
|
| LogP |
4.7
|
| Hydrogen Bond Donor Count |
1
|
| Hydrogen Bond Acceptor Count |
6
|
| Rotatable Bond Count |
11
|
| Heavy Atom Count |
36
|
| Complexity |
818
|
| Defined Atom Stereocenter Count |
0
|
| SMILES |
COC(=O)CCCCC(=O)NCCN1C(=O)C2=C3C(=C(C=C2)SC4=CC=C(C=C4)Br)C=CC=C3C1=O
|
| InChi Key |
HZZXWFWVQWMGAR-UHFFFAOYSA-N
|
| InChi Code |
InChI=1S/C27H25BrN2O5S/c1-35-24(32)8-3-2-7-23(31)29-15-16-30-26(33)20-6-4-5-19-22(14-13-21(25(19)20)27(30)34)36-18-11-9-17(28)10-12-18/h4-6,9-14H,2-3,7-8,15-16H2,1H3,(H,29,31)
|
| Chemical Name |
methyl 6-[2-[6-(4-bromophenyl)sulfanyl-1,3-dioxobenzo[de]isoquinolin-2-yl]ethylamino]-6-oxohexanoate
|
| HS Tariff Code |
2934.99.9001
|
| 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)
|
| Solubility (In Vitro) |
DMSO : 17.86 mg/mL (31.36 mM)
|
|---|---|
| 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 | 1.7560 mL | 8.7801 mL | 17.5602 mL | |
| 5 mM | 0.3512 mL | 1.7560 mL | 3.5120 mL | |
| 10 mM | 0.1756 mL | 0.8780 mL | 1.7560 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.
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
