| Size | Price | Stock | Qty |
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| 10mg |
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| 50mg |
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| Targets |
Mcl-1 Bim
Mcl-1 (myeloid cell leukemia-1). ML311 selectively inhibits the interaction between Mcl-1 and Bim, a pro-apoptotic protein. By disrupting this interaction, ML311 promotes apoptosis in Mcl-1-dependent cancer cells. |
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| ln Vitro |
ML311 potently and with a usually high maximal effect (>80%) stops the viability of numerous types of Mcl-1 primed cells, such as MCL-1-1780 (EC50=0.31 μM), DHL-6 (EC50=3.3 μM), and NCI-H929 (EC50=1.6 μM). In a leukemia-derived cell line that is especially dependent on Bcl-2 function (Bcl2-1863, EC50=1.1 μM), ML311 also exhibits activity. With GI50<900 nM for nine cell types (RPMI-8226, SR, NCI-H322M, NCI-H60, HCC-2998, KM12, SF-295, U251, PC-3 cell lines) and <2 μM for fourteen more, ML311 has substantial growth inhibitory effects in a wide range of cell lines [1].
ML311 potently inhibits the viability of Mcl-1-primed cells, including MCL-1-1780 (EC50: 0.31 µM), NCI-H929 (EC50: 1.6 µM), and DHL-6 (EC50: 3.3 µM), generally exhibiting maximal effects >80%. It has an IC50 of 0.31 µM for Mcl-1 in a fluorescence polarization assay. |
| ln Vivo |
In vivo activity data for ML311 is not extensively detailed in the literature. As an inhibitor of the Mcl-1/Bim interaction, it is expected to show antitumor efficacy in animal models of Mcl-1-dependent cancers. Its selectivity for Mcl-1 over Bcl-xL suggests it may have a favorable safety profile.
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| Enzyme Assay |
In vitro binding assays are performed using fluorescence polarization (FP) or TR-FRET technologies. Recombinant Mcl-1 protein and a labeled Bim peptide are used. The compound's ability to displace the labeled peptide is measured, and IC50 values are calculated.
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| Cell Assay |
Cells (e.g., Mcl-1-primed cancer cell lines) are treated with ML311. Cell viability is measured using MTT or CellTiter-Glo assays. Apoptosis is assessed by Annexin V/PI staining and caspase activation. Bim release from Mcl-1 is assessed by co-immunoprecipitation.
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| Animal Protocol |
In vivo efficacy studies are performed in mouse xenograft models using Mcl-1-dependent cancer cell lines. ML311 is administered intraperitoneally or orally. Tumor volume is measured by calipers. Tumors are harvested for histology and biomarker analysis (e.g., apoptosis markers). Body weight and clinical signs are monitored.
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| ADME/Pharmacokinetics |
ML311 has a molecular weight of 415.45 and a molecular formula of C23H24F3N3O. It is soluble in DMSO. Detailed pharmacokinetic parameters such as oral bioavailability and half-life are available from specialized databases. It is stored at -20°C.
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| Toxicity/Toxicokinetics |
Detailed toxicological profiles of ML311 are not extensively reported. As a research compound, it is expected to have a manageable safety profile at the concentrations used in cell-based assays. Its selectivity for Mcl-1 over Bcl-xL suggests it may have fewer on-target toxicities, such as thrombocytopenia, associated with Bcl-xL inhibition.
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| References | |
| Additional Infomation |
ML311 is a research-grade Mcl-1/Bim interaction inhibitor. It is used in cancer research to study apoptosis and Mcl-1-dependent cancer cell survival. It is not approved for clinical use. Its molecular formula is C23H24F3N3O and its molecular weight is 415.45.
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| Molecular Formula |
C23H24F3N3O
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|---|---|
| Molecular Weight |
415.451375961304
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| Exact Mass |
415.19
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| Elemental Analysis |
C, 66.49; H, 5.82; F, 13.72; N, 10.11; O, 3.85
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| CAS # |
315698-17-0
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| PubChem CID |
3384730
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| Appearance |
White to off-white solid powder
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| LogP |
4.4
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
7
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| Rotatable Bond Count |
4
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| Heavy Atom Count |
30
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| Complexity |
544
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| Defined Atom Stereocenter Count |
0
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| SMILES |
CCN1CCN(CC1)C(C2=CC=C(C=C2)C(F)(F)F)C3=C(C4=C(C=CC=N4)C=C3)O
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| InChi Key |
NGAPBLRRJSKIRT-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C23H24F3N3O/c1-2-28-12-14-29(15-13-28)21(17-5-8-18(9-6-17)23(24,25)26)19-10-7-16-4-3-11-27-20(16)22(19)30/h3-11,21,30H,2,12-15H2,1H3
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| Chemical Name |
7-[(4-Ethylpiperazin-1-yl)-[4-(trifluoromethyl)phenyl]methyl]quinolin-8-ol
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| Synonyms |
ML311; ML-311; ML 311; EU-5346; EU 5346; EU5346.
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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 : 67.5 mg/mL (162.47 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.25 mg/mL (5.42 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (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 22.5 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.25 mg/mL (5.42 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (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 22.5 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. View More
Solubility in Formulation 3: ≥ 2.25 mg/mL (5.42 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.4070 mL | 12.0351 mL | 24.0703 mL | |
| 5 mM | 0.4814 mL | 2.4070 mL | 4.8141 mL | |
| 10 mM | 0.2407 mL | 1.2035 mL | 2.4070 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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