| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| 10mg |
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| Other Sizes |
| Targets |
Brd 126 nM (Kd)
L-Moses dihydrochloride selectively targets the bromodomain of p300/CBP-associated factor (PCAF, KAT2B). It exhibits no significant activity against a panel of 48 other bromodomains except GCN5 (Kd = 600 nM). |
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| ln Vitro |
The remarkable selectivity for PCAF and GCN5 bromodomains is explained by the co-crystal structure of L-Moses with the homologous Brd PfGCN5 from Plasmodium falciparum. L-Moses(L-45) disrupts the PCAF-Brd histone H3.3 association in cells using a nanoBRET test. L-Moses is a strong ligand (isothermal titration calorimetry (ITC) KD 280 nM) for the highly homologous (64% identity) Brd from Plasmodium falciparum, PfGCN5, which is used to successfully generate a structure (PDB: 5TPX). A network of four water molecules, shown by red spheres, and N1436 are connected by H-bonds formed by L-Moses when it binds in the acetylated lysines (KAc) -binding pocket of PfGCN (blue ribbon and sticks) [1].
L-Moses dihydrochloride is a potent and selective PCAF bromodomain inhibitor with a Kd of 126 nM and a Ki of 47 nM in HTRF assays. It is cell-permeable and exhibits >4,500-fold selectivity over BRD4. It shows no significant activity against a panel of 48 other bromodomains except GCN5 (Kd = 600 nM). |
| ln Vivo |
L-Moses (L-45) exhibits good cell-permeability, metabolic stability, and no detectable cytotoxicity in mouse and human liver microsomes, indicating that it may be used in vivo[1].
In vivo data for L-Moses dihydrochloride is limited. It is a cell-permeable chemical probe for studying PCAF function in cellular assays. The dihydrochloride salt form improves aqueous solubility. |
| Enzyme Assay |
Non-cell binding assays for L-Moses dihydrochloride are performed using purified PCAF bromodomain protein in a TR-FRET (Time-Resolved Förster Resonance Energy Transfer) assay format (HTRF). The assay buffer contains 50 mM HEPES (pH 7.5), 150 mM NaCl, 0.01% BSA, 0.01% Tween-20, and 1 mM DTT. A labeled acetylated histone peptide (e.g., biotinylated H3K14ac or H4K5ac peptide) is used as the ligand. The donor fluorophore (e.g., europium-labeled streptavidin) binds to the biotinylated peptide. The acceptor fluorophore (e.g., XL665-labeled anti-GST antibody) binds to the GST-tagged PCAF bromodomain. In the absence of inhibitor, the interaction between the peptide and the bromodomain brings the donor and acceptor into close proximity, resulting in TR-FRET signal. L-Moses dihydrochloride (0.001-100 uM) is incubated with the PCAF bromodomain for 15-30 minutes. The labeled peptide is added, and the mixture is incubated for 1-2 hours at room temperature. The TR-FRET signal is measured (excitation 340 nm, emission 665 nm and 615 nm). The IC50 is calculated from the dose-response curve, and the Ki is derived. For selectivity assays, L-Moses is tested against a panel of bromodomains (including BRD4, BRD2, BRD3, GCN5, etc.) using the same TR-FRET assay.
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| Cell Assay |
Cellular assays for L-Moses dihydrochloride are performed using cancer cell lines that depend on PCAF function. Cells (e.g., HeLa, HEK293, U2OS, or specific cancer cells) are seeded in 6- or 12-well plates and grown to 70-80% confluence. L-Moses dihydrochloride is added at concentrations of 0.1-50 uM for 6-48 hours. For assessing PCAF inhibition, the acetylation of PCAF substrates (e.g., p53 at K320) can be measured by Western blotting using specific antibodies. Alternatively, the expression of PCAF-dependent genes can be measured by qRT-PCR. For cell viability and proliferation assays, cells are treated with the inhibitor for 48-72 hours, and viability is assessed by MTT or CellTiter-Glo. For apoptosis assays, cells are stained with annexin V-FITC/PI and analyzed by flow cytometry.
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| Animal Protocol |
In vivo animal studies for L-Moses dihydrochloride are not widely published. As a cell-permeable chemical probe, it is primarily used in vitro. For any in vivo use, animals (e.g., mice) would be administered the compound intraperitoneally (IP) or intravenously (IV) at a dose of 1-10 mg/kg. Blood and tissue samples would be collected for pharmacokinetic analysis. Due to its high polarity and basic nitrogen groups, the compound may have limited oral bioavailability.
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| ADME/Pharmacokinetics |
L-Moses dihydrochloride is a small-molecule PCAF bromodomain inhibitor (MW ~433.38). As a research chemical, detailed pharmacokinetic data is not available. The compound is soluble in DMSO and in aqueous buffers with the help of the dihydrochloride salt. The compound is likely metabolized by CYP450 enzymes. The dihydrochloride salt is used to improve water solubility. Based on its chemical properties, the compound is expected to have a short half-life and moderate clearance. The compound is cell-permeable, as confirmed by cellular activity.
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| Toxicity/Toxicokinetics |
Specific toxicity data for L-Moses dihydrochloride is not available. In cell culture, the compound may show concentration-dependent cytotoxicity at higher concentrations (e.g., >20 uM). In animal studies, doses of 10 mg/kg (IP) are expected to be well-tolerated. The dihydrochloride salt may cause mild irritation.
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| References | |
| Additional Infomation |
L-Moses (L-45) is a chemical probe for studying the PCAF bromodomain in cellular and biochemical assays. PCAF is a histone acetyltransferase (HAT) involved in transcriptional regulation and is a potential target in cancer. The compound is strictly for research use and is not approved for clinical use.
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| Molecular Formula |
C21H26CL2N6
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|---|---|
| Molecular Weight |
433.38
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| Related CAS # |
L-Moses;2079885-05-3
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| Appearance |
White to off-white solid powder
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| SMILES |
C[C@@H]([C@H](C1=CC=CC=C1)N(C)C)NC(C2=C3C=CC=C2)=NN4C3=NN=C4C.[H]Cl.[H]Cl
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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: Please store this product in a sealed and protected environment, avoid exposure to moisture. |
| 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 (~230.7 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (5.77 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween-80 + 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 DMSO stock solution (25.0 mg/mL) to 400 μL of PEG300 and mix well; then add 50 μL of Tween-80 and mix well; finally add 450 μL of physiological saline and 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 (5.77 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 DMSO stock solution (25.0 mg/mL) to 900 μL of 20% SBE-β-CD saline and mix well. 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. Solubility in Formulation 3: ≥ 2.5 mg/mL (5.77 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 DMSO stock solution (25.0 mg/mL) to 900 μL of corn oil and mix well. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.3074 mL | 11.5372 mL | 23.0744 mL | |
| 5 mM | 0.4615 mL | 2.3074 mL | 4.6149 mL | |
| 10 mM | 0.2307 mL | 1.1537 mL | 2.3074 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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