MS023 |
رقم الكتالوجGC10099
One-Click Copy Product Info
|
MS023 هو مثبط فعال وانتقائي وفعّال في الخلايا لإنزيمات بروتين أرجنين المثيل ترانسفيراز (PRMTs) من النوع I.
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 1831110-54-3
Sample solution is provided at 25 µL, 10mM.
_1-3.$$$39978408@51.jpg');)
_1-9.$$$38538795@65.jpg');)
_1-9.$$$39112701@51.jpg');)
_1-7.$$$37316672@70.jpg');)
_366-372.$$$36198801@70.jpg');)
.$$$38565142@65.jpg');)
_1867-1883.$$$33248023@67.jpg');)
_eads6055.$$$39977546@45.jpg');)
_eadm9805.$$$40080571@45.jpg');)
_eadj3020.$$$39666821@45.jpg');)
_1-20.$$$39757301@28.jpg');)
_1-24.$$$38898113@28.jpg');)
_273-287.$$$36806353@46.jpg');)
_1-16.$$$37156877@44.jpg');)
_1-19.$$$37460805@44.jpg');)
_1291-1307.$$$34518654@46.jpg');)
MS023 is a potent, selective, and cell-active inhibitor of type I protein arginine methyltransferases (PRMTs) [1]. with IC50s of 30, 119, 83, 4 and 5 nM for PRMT1, PRMT3, PRMT4, PRMT6, and PRMT8, respectively [1].
MS023 treatment (48 h exposure) potently and concentration dependently reduced cellular levels of H4R3me2a (IC50 = 9 ± 0.2 nM), PRMT1 is the main contributor to H4R3 (histone H4 arginine 3) asymmetric dimethylation (H4R3me2a) in cells. MS023 (20 h exposure) concentration dependently reduced the H3R2me2a mark in HEK293 cells (IC50 = 56 ± 7 nM), PRMT6 robustly increased endogenous asymmetric dimethylation of H3R2 (histone H3 arginine 2) [1]. MS023 (1µM, 24h) significantly reduced SARS-CoV-2 replication in VeroE6 cells by inhibition of arginine methylation [2]. MS023 (150,175,200µM) for 48 h treated DLD1 and HCT116 cells increased levels of active form of caspase 3 and PARP degradation as representative apoptosis-related proteins [3].
MS023 treatment on mice model of spinal muscular atrophy (SMA) with both 2 mg/kg and 5 mg/kg resulted in significant increase in survival, with the 2 mg/kg dose achieving the best effect (median: 10 days), compared to both untreated (median: 7) and vehicle-treated (median: 6 days) mice. Mice treated with MS023 also showed an improvement in the disease-associated weight loss [4]. Once-daily dosing of 60 mg kg-1 MS023 initiated in mice with palpable tumors significantly reduced tumor growth and final tumor weight on MDA-MB-468 xenograft mice [5].
References:
[1]. Eram M S, Shen Y, Szewczyk M M, et al. A potent, selective, and cell-active inhibitor of human type I protein arginine methyltransferases[J]. ACS chemical biology, 2016, 11(3): 772-781.
[2]. Cai T, Yu Z, Wang Z, et al. Arginine methylation of SARS-Cov-2 nucleocapsid protein regulates RNA binding, its ability to suppress stress granule formation, and viral replication[J]. Journal of Biological Chemistry, 2021, 297(1).
[3]. Lim Y, Lee J Y, Ha S J, et al. Proteome-wide identification of arginine methylation in colorectal cancer tissues from patients[J]. Proteome Science, 2020, 18(1): 1-11.
[4]. Kordala A J, Ahlskog N, Hanifi M, et al. Type I PRMT inhibitor MS023 promotes SMN2 exon 7 inclusion and synergizes with nusinersen to rescue the phenotype of SMA mice[J]. bioRxiv, 2022.
[5]. Wu Q, Nie D Y, Ba-Alawi W, et al. PRMT inhibition induces a viral mimicry response in triple-negative breast cancer[J]. Nature Chemical Biology, 2022: 1-10.
| Cell experiment [1]: | |
Cell lines | Two human colon carcinoma cell lines DLD1 and HCT116 |
Preparation Method | CRC cells were seeded into 96-well plates at a density of 5 × 103 cells in 100 µl medium per well and cultured in 5% humidified atmosphere at 37 °C. After 24 h incubation, MS023 alone or combined with SN-38 was treated with increasing concentrations for 2 days. |
Reaction Conditions | 0-200µM for 2 days |
Applications | Concentration of MS023 (125 µM) which resulted in about 40% reduction of CRC cell growth, MS023 significantly enhanced SN-38 cytotoxicity in DLD1 and HCT116 cells. |
| Animal experiment [2]: | |
Animal models | Severe combined immunodeficient mice |
Preparation Method | 7 × 106 MDA-MB-468 cells were injected into the mice, MS023 was prepared at 5% N-Methyl-2-pyrrolidone (NMP), 20% captisol (wt/vol), 20% PEG-400 and 55% normal saline and administered to the mice by intraperitoneal injection. Tumors grown to a detectable size, as assessed by palpation (~2 mm in diameter), and started to treat with 60 mg kg–1 MS023 daily for a total of 5 weeks. |
Dosage form | Intraperitoneal injection, 60 mg kg-1d-1 for 5 weeks. |
Applications | Once-daily dosing of 60 mg kg-1 MS023 initiated in mice with palpable tumors significantly reduced tumor growth and final tumor weight. |
References: | |
| Cas No. | 1831110-54-3 | SDF | |
| Chemical Name | N1-((4-(4-isopropoxyphenyl)-1H-pyrrol-3-yl)methyl)-N1-methylethane-1,2-diamine | ||
| Canonical SMILES | NCCN(C)CC1=CNC=C1C2=CC=C(OC(C)C)C=C2 | ||
| Formula | C17H25N3O | M.Wt | 287.4 |
| الذوبان | ≥ 28.7mg/mL in DMSO | Storage | Store at -20°C |
| General tips | Please select the appropriate solvent to prepare the stock solution according to the
solubility of the product in different solvents; once the solution is prepared, please store it in
separate packages to avoid product failure caused by repeated freezing and thawing.Storage method
and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored
at -20°C, please use it within 1 month. To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time. |
||
| Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. | ||
| Prepare stock solution | |||
|
1 mg | 5 mg | 10 mg |
| 1 mM | 3.4795 mL | 17.3974 mL | 34.7947 mL |
| 5 mM | 695.9 μL | 3.4795 mL | 6.9589 mL |
| 10 mM | 347.9 μL | 1.7397 mL | 3.4795 mL |
Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)
g
μL
Step 2: Enter the in vivo formulation (This is only the calculator, not formulation. Please contact us first if there is no in vivo formulation at the solubility Section.)
Calculation results:
Working concentration: mg/ml;
Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid 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 master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL saline, mix and clarify.
Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.
Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such as vortex, ultrasound or hot water bath can be used to aid dissolving.
3. All of the above co-solvents are available for purchase on the GlpBio website.
Quality Control & SDS
- View current batch:
- Purity: >98.00% Appearance: A solid
- COA (Certificate of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Average Rating: 5 (Based on Reviews and 17 reference(s) in Google Scholar.)