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| 5mg | ||
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| Targets |
ML 2-14 targets the epigenetic reader protein Bromodomain-containing Protein 4 (BRD4). By binding to BRD4 and simultaneously recruiting an E3 ubiquitin ligase via its ligand, it facilitates the transfer of ubiquitin to BRD4, marking it for proteasomal degradation rather than simple enzymatic inhibition.
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| ln Vitro |
In 231MFP breast cancer cells, ML 2-14 with a C4 alkyl linker demonstrated significant BRD4 degradation; the DC50 values for the long and short isoforms of BRD4 were 36 and 14 nM, respectively [1].
ML 2-14 effectively degrades BRD4 in 231MFP breast cancer cells, with DC₅0 values (the concentration required for 50% degradation) of 36 nM for the long isoform of BRD4 and 14 nM for the short isoform. This degradation can be reversed by the proteasome inhibitor Bortezomib, confirming that the effect is mediated by the ubiquitin-proteasome pathway. |
| ln Vivo |
Specific in vivo efficacy data for ML 2-14 is not provided in the available literature. As a PROTAC, its in vivo activity would be evaluated in tumor xenograft mouse models, where one would measure tumor growth inhibition, BRD4 target knockdown by Western blotting of tumor lysates, and assessment of downstream pharmacodynamic markers like c-Myc expression.
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| Cell Assay |
Standard cellular protocols for assessing PROTAC activity involve seeding cells (e.g., 231MFP breast cancer cells) in 6- or 96-well plates. The next day, cells are treated with a dose titration of ML 2-14 for a defined period (e.g., 4-24 hours). Cells are then lysed, and the lysates are analyzed by Western blotting using an anti-BRD4 antibody. Quantitative analysis of the Western blot bands is used to determine the DC₅0 values for the degradation of target proteins. To validate the mechanism, cells can be co-treated with ML 2-14 and the proteasome inhibitor Bortezomib.
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| Animal Protocol |
A typical in vivo protocol for a PROTAC like ML 2-14 would involve dosing mice bearing subcutaneous tumor xenografts. The compound would be administered, often intraperitoneally or orally, at a range of doses (e.g., 10-100 mg/kg). After treatment, tumors are excised, and target protein levels are assessed by immunohistochemistry or Western blot. Efficacy is monitored by measuring tumor growth reduction.
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| ADME/Pharmacokinetics |
ML 2-14 is a small molecule with a molecular weight of approximately 848.13 (based on its molecular formula C40H3₈BrCl2N₇O3S). For in vivo studies, it can be formulated in co-solvent systems such as 10% DMSO + 40% PEG300 + 5% Tween 80 + 45% saline, or 10% DMSO + 90% corn oil, which are standard vehicles for poorly water-soluble compounds.
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| Toxicity/Toxicokinetics |
PROTACs are known for their "event-driven" pharmacology, which often leads to a favorable safety profile as they can be effective at lower concentrations and durations than traditional inhibitors. However, the potential for off-target degradation and toxicity is a key concern. No specific toxicology data is available for ML 2-14, and as a research tool, its safety profile is not intended for human use.
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| References |
[1]. Luo M, et al. Chemoproteomics-enabled discovery of covalent RNF114-based degraders that mimic natural product function. Cell Chem Biol. 2021;28(4):559-566.e15.
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| Additional Infomation |
ML 2-14 is a cutting-edge PROTAC research tool for the study of BRD4-related biology. BRD4 is a key oncogene and a well-validated target in various cancers, including NUT midline carcinoma and acute myeloid leukemia. This compound is strictly for laboratory research and is not intended for diagnostic, therapeutic, or human use. It has not been approved by any regulatory agency.
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| Molecular Formula |
C40H38BRCL2N7O3S
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| Appearance |
White to off-white solid powder
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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 (~117.97 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (2.95 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 25.0 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: ≥ 2.5 mg/mL (2.95 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (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 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
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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