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| Targets |
MS37452 targets Chromobox homolog 7 (CBX7), a component of the Polycomb repressive complex 1 (PRC1) that recognizes and binds to trimethylated histone H3 lysine 27 (H3K27me3). CBX7 plays a key role in gene transcription in cellular processes related to stem cell self-renewal, differentiation, and tumor progression. MS37452 is a competitive inhibitor of CBX7 chromodomain binding to H3K27me3, with a Kd of 27.7 μM. By disrupting CBX7 binding, MS37452 can derepress transcription of PRC1 target genes such as p16/CDKN2A.
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| ln Vitro |
In comparison to the DMSO control, MS37452 (125-500 μM; 12 hours) significantly elevated INK4A/ARF transcript levels at 250 μM and 500 μM by 25% and 60%, respectively [1]. After two hours of treatment on human PC3 prostate cancer cells, CBX7 occupancy at the INK4A/ARF site is reduced by MS37452 (250 μM) [1]. Compared to DMSO therapy and single drug treatment, the combination of MS37452 (200 µM; 5 days) plus doxorubicin resulted in a prolonged decrease in cell viability [2]. When combined with doxorubicin, MS37452 (200 µM; 5 days)—a CBX7 chromodomain inhibitor (CBX7i)—is a unique treatment approach [2].
In vitro, MS37452 (250 μM; 2 hours) treats human PC3 prostate cancer cells for 2 hours, reducing CBX7 occupancy across the INK4A/ARF locus. This displacement leads to derepression of transcription of the polycomb repressive complex target gene p16/CDKN2A in prostate cancer cells. The compound's activity is typically assessed by chromatin immunoprecipitation (ChIP) to measure CBX7 occupancy, and by qRT-PCR or Western blot to measure p16/CDKN2A expression. MS37452 is a valuable tool for studying the role of CBX7 and PRC1 in gene regulation and cancer. |
| ln Vivo |
In vivo, MS37452 has been studied for its potential to reactivate tumor suppressor genes such as p16/CDKN2A. As a CBX7 inhibitor, it can disrupt PRC1-mediated gene repression and potentially inhibit tumor progression. Specific in vivo efficacy data are limited in the published literature. MS37452 is a research tool for studying the role of CBX7 and Polycomb repressive complexes in cancer and development.
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| Enzyme Assay |
In vitro binding assays for MS37452 typically involve measuring the inhibition of CBX7 chromodomain binding to H3K27me3 peptides. A typical protocol: recombinant CBX7 chromodomain protein is incubated with biotinylated H3K27me3 peptide and varying concentrations of MS37452 (0.1 μM to 1 mM) in binding buffer for 60 minutes at room temperature. Binding is detected by AlphaScreen, fluorescence polarization, or surface plasmon resonance (SPR). IC₅₀ and Kd values are calculated from competition curves. Positive controls include unlabeled H3K27me3 peptide. Each concentration is tested in triplicate.
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| Cell Assay |
RT-PCR[1]
Cell Types: PC3 Cell Tested Concentrations: 125-500 μM Incubation Duration: 12 hrs (hours) Experimental Results: INK4A/ARF expression was up-regulated by up to 25% and 60% at 250 μM and 500 μM, respectively. Cell viability assay [2] Cell Types: Glioblastoma multiforme (GBM) U118MG Cell Tested Concentrations: PRT4165 40 µM, PTC209 200 nM, DZnep 25 µM, GSK343 400 nM, MS37452 200 µM, Doxorubicin 200 nM, Temozolomide 50 µM, SAHA 1 µM Incubation Duration: 5 days Experimental Results: Several combinations were identified that resulted in a sustained decrease in cell viability compared to DMSO treatment and single drug treatment (SAHA/TMZ and MS37452/doxorubicin). In vitro cell-based assays for MS37452 are performed using prostate cancer cell lines such as PC3 or LNCaP. A typical protocol: cells are seeded in 6-well plates and treated with MS37452 at concentrations ranging from 10 to 500 μM for 2-24 hours. CBX7 occupancy at the INK4A/ARF locus is assessed by chromatin immunoprecipitation (ChIP) using anti-CBX7 antibodies. p16/CDKN2A mRNA and protein levels are measured by qRT-PCR and Western blot. Cell viability is assessed using MTT assays. Each condition is tested in duplicate, and experiments are repeated at least twice. |
| Animal Protocol |
In vivo animal studies for MS37452 are limited. If conducted, a typical protocol would involve administering MS37452 to mice bearing prostate cancer xenografts via intraperitoneal injection at doses of 10-100 mg/kg, daily, for 2-4 weeks. Tumor volumes would be measured with calipers, and tumor tissues would be harvested for analysis of p16/CDKN2A expression and CBX7 occupancy. However, specific in vivo studies for MS37452 have not been extensively published. The compound is primarily used for in vitro studies.
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| ADME/Pharmacokinetics |
Pharmacokinetic properties of MS37452 have not been fully characterized. Information concerning product stability, particularly in solution, has rarely been reported. The compound is soluble in DMSO. Its plasma half-life, volume of distribution, protein binding, and oral bioavailability remain unknown. The compound is a research-grade chemical and has not been developed for clinical applications. It should be stored as recommended by the manufacturer.
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| Toxicity/Toxicokinetics |
Toxicological data for MS37452 are limited. As a research chemical, it has not undergone formal toxicology testing. Standard laboratory safety precautions should be followed when handling MS37452: use of personal protective equipment (gloves, safety goggles, lab coat) and handling in a well-ventilated fume hood. The compound should be stored at -20°C for long-term stability. No genotoxicity, carcinogenicity, or reproductive toxicity data are available. Researchers should consult the safety data sheet (SDS) before handling.
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| References | |
| Additional Infomation |
Additional information for MS37452: The compound has a CAS number of 423748-02-1. Its molecular formula is C₂₂H₂₆N₂O₅ and molecular weight is 398.45 g/mol. It is a selective CBX7 modulator that disrupts CBX7ChD binding to H3K27me3. Kd = 27.7 μM. It derepresses p16/CDKN2A transcription in prostate cancer cells. It is for research use only and is not approved for clinical applications. No FDA approvals exist.
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| Molecular Formula |
C22H26N2O5
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| Molecular Weight |
398.45
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| Exact Mass |
398.184
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| Elemental Analysis |
C, 66.32; H, 6.58; N, 7.03; O, 20.08
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| CAS # |
423748-02-1
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| PubChem CID |
1072048
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| Appearance |
Off-white to light yellow solid powder
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| Density |
1.2±0.1 g/cm3
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| Boiling Point |
628.8±55.0 °C at 760 mmHg
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| Flash Point |
334.1±31.5 °C
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| Vapour Pressure |
0.0±1.8 mmHg at 25°C
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| Index of Refraction |
1.575
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| LogP |
2.29
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| Hydrogen Bond Donor Count |
0
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| Hydrogen Bond Acceptor Count |
5
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| Rotatable Bond Count |
6
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| Heavy Atom Count |
29
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| Complexity |
549
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| Defined Atom Stereocenter Count |
0
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| SMILES |
CC1=CC(=CC=C1)OCC(=O)N2CCN(CC2)C(=O)C3=C(C(=CC=C3)OC)OC
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| InChi Key |
LUMCNRKHZRYQOV-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C22H26N2O5/c1-16-6-4-7-17(14-16)29-15-20(25)23-10-12-24(13-11-23)22(26)18-8-5-9-19(27-2)21(18)28-3/h4-9,14H,10-13,15H2,1-3H3
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| Chemical Name |
1-[4-(2,3-dimethoxybenzoyl)piperazin-1-yl]-2-(3-methylphenoxy)ethanone
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| Synonyms |
MS 37452; MS-37452; MS37452
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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 (~250.97 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (6.27 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 (6.27 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 25.0 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. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.5097 mL | 12.5486 mL | 25.0973 mL | |
| 5 mM | 0.5019 mL | 2.5097 mL | 5.0195 mL | |
| 10 mM | 0.2510 mL | 1.2549 mL | 2.5097 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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