Navlimetostat
Based on 3 publication(s) in Google Scholar
Navlimetostat is a potent, orally active, selective PRMT5-MTA complex inhibitor, with IC50 of 3.6 and 20.5 nM for PRMT5-MTA and PRMT5. Navlimetostat binds to the PRMT5-MTA complex, with KD value of 0.14 pM. Navlimetostat shows antineoplastic activity in vitro and in vivo, and can be used for cancer study.
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- Pureté: 99.16%
- CAS No.: 2630904-45-7
- Formule: C23H18ClFN6O2
- Masse moléculaire:464.88
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Stockage:Powder -20°C, 3 years , 4°C, 2 years ; In solvent -80°C, 6 months , -20°C, 1 month
To place orders, for customer services and technical support, please contact: MedChemExpress USA
Tel: 609-228-6898 E-mail: [email protected] [email protected]
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Activité biologique
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Chemical Information
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Solvant et solubilité
- Pureté et documentation
- Références
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Help & FAQs
Publications Citing Use of MedChemExpress (MCE) Navlimetostat
More
Customer Validation & Images
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Cell Migration/Invasion Assay
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Cell Proliferation/Viability Assay
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Bio/Physico-chemical Assay
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In Vivo Efficacy Study
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Cell Proliferation/Viability Assay
Voir tous les produits spécifiques à Isoform Histone Methyltransferase
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Activité biologique
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PRMT5 |
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Cell Line
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Type | Value | Description | References |
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| HCT-116 | IC50 |
12 nM
Compound: MRTX1719
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Antiproliferative activity against MTAP knockout human HCT-116 cells assessed as cell viability after 10 days by CellTiter-Glo assay
Antiproliferative activity against MTAP knockout human HCT-116 cells assessed as cell viability after 10 days by CellTiter-Glo assay
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[PMID: 35926325] |
| HCT-116 | IC50 |
890 nM
Compound: MRTX1719
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Antiproliferative activity against human HCT-116 cells expressing wild type MTAP assessed as cell viability after 10 days by CellTiter-Glo assay
Antiproliferative activity against human HCT-116 cells expressing wild type MTAP assessed as cell viability after 10 days by CellTiter-Glo assay
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[PMID: 35926325] |
| HepG2 | IC50 |
6600 nM
Compound: MRTX1719
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Antiproliferative activity against human HepG2 cells assessed as inhibition of cell viability measured after 120 hrs CellTiter-Glo assay
Antiproliferative activity against human HepG2 cells assessed as inhibition of cell viability measured after 120 hrs CellTiter-Glo assay
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[PMID: 35926325] |
Navlimetostat (10 day) inhibits the PRMT5 activity and in MTAP-deleted HCT116 cells not wild type cells, with the IC50 of 8 nM[1].
Navlimetostat (10 day) inhibits the cell viability of MTAP del HCT116 cells with an IC50 value of 12 nM and parental HCT116 cells with an IC50 value of 890 nM[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
Pharmacokinetic Analysis [2]
| Model | Route | Dose (mg/kg) | Cltotal (mL/min/kg) | Vdss (L/kg) | t1/2 (h) |
| CD-1 mouse. | i.v. | 3 | 83 | 6.3 | 1.5 |
| Beagle dog | i.v. | 2 | 14 | 3.4 | 4.8 |
| Cynomolgus monkey | i.v. | 2 | 15 | 2.3 | 6.1 |
| Model | Route | Dose (mg/kg) | Cmax (ug/mL) | AUCinf (h*ug/mL) | F (%) |
| CD-1 mouse. | p.o. | 30 | 1.16 | 4.85 | 80 |
| Beagle dog | p.o. | 10 | 1.40 | 7.47 | 59 |
| Cynomolgus monkey | p.o. | 10 | / | / | 41 |
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:Lu-99 (an MTAP/CDKN2A-deleted human lung cancer cell line ) xenograft tumor models[2]Dosage:12.5, 25, 50, and 100 mg/kg/d, 21 dayAdministration:Oral gavageResult:Reduced the tumor volume with 86% tumor growth inhibition (TGI) at 50 mg/kg and 88% TGI at 100 mg/kg.
| NCT Number | Sponsor | Condition | Start Date |
Phase
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|---|---|---|---|---|
| NCT01329991 | Plexxikon| | 2011-05 | PHASE1 |
Chemical Information
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CAS No. 2630904-45-7
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Appearance Solid
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Masse moléculaire 464.88
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Formule C23H18ClFN6O2
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Color White to light yellow
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SMILES
FC1=C(C=C(C(C#N)=[C@]1[C@]2=C(C3=CC=C4C(C(CN)=NNC4=O)=C3)C=NN2C)OC5CC5)Cl
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Synonyms
MRTX-1719; BMS-986504
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Livraison
Room temperature in continental US; may vary elsewhere.
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Stockage
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month
Publications (3)
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Journal Impact Factor
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Most Recent
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MedComm (2020)
SCR-7952, a highly selective MAT2A inhibitor, demonstrates synergistic antitumor activities in combination with the S-adenosylmethionine-competitive or the methylthioadenosine-cooperative protein arginine methyltransferase 5 inhibitors in methylthioadenosine phosphorylase-deleted tumors. [Abstract]2024 Sep 20;5(10):e705. PMID: 39309689
Navlimetostat purchased from MedChemExpress. Usage Cited in: MedComm (2020). 2024 Sep 20;5(10):e705. [Abstract]
Drug dose-response curves for proliferation inhibition and Bliss plots showing the synergistic effects of SCR-7952 in combination with MRTX-1719 on HCT116 MTAP-/- cells over 8 days.
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Cancer Med
Inhibitory Effect of PRMT5/MTA Inhibitor on MTAP-Deficient Glioma May Be Influenced by Surrounding Normal Cells. [Abstract]2024 Dec;13(24):e70526. PMID: 39711357
Navlimetostat purchased from MedChemExpress. Usage Cited in: Cancer Med. 2024 Dec;13(24):e70526. [Abstract]
MRTX1719 (0–10000 nM, 8 days) inhibited the growth of the above five cell types.
Navlimetostat purchased from MedChemExpress. Usage Cited in: Cancer Med. 2024 Dec;13(24):e70526. [Abstract]
MRTX1719 (0–10000 nM, 14 days) inhibited the growth of the above four cell types.
Navlimetostat purchased from MedChemExpress. Usage Cited in: Cancer Med. 2024 Dec;13(24):e70526. [Abstract]
Following subcutaneous injection of MRTX1719 (10 mg/kg, intraperitoneal injection), the drug concentration in the brain reached its maximum approximately 1 h after administration. The brain-to-plasma concentration ratio of MRTX1719 peaked at 4 h post-administration (brain (A) and serum (B); brain-to-plasma concentration ratio (C)).
Navlimetostat purchased from MedChemExpress. Usage Cited in: Cancer Med. 2024 Dec;13(24):e70526. [Abstract]
MRTX1719 (10 mg/kg, intraperitoneal injection) reduced the volume of Hs683-transplanted tumors without reducing the body weight of the mice.
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Solvant et solubilité
DMSO : 100 mg/mL (215.11 mM; Need ultrasonic; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
Select the appropriate dissolution method based on your experimental animal and administration route.
- For the following dissolution methods, please ensure to first prepare a clear stock solution using an In Vitro approach and then sequentially add co-solvents:
- To ensure reliable experimental results, the clarified stock solution can be appropriately stored based on storage conditions. As for the working solution for In Vivo experiments, it is recommended to prepare freshly and use it on the same day.
- The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.
Add each solvent one by one: 10% DMSO 40% PEG300 5% Tween-80 45% Saline
Solubility: ≥ 2 mg/mL (4.30 mM); Clear solution
This protocol yields a clear solution of ≥ 2 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (20.0 mg/mL) to 400 μL PEG300, and mix evenly; then add 50 μL Tween-80 and mix evenly; then add 450 μL Saline to adjust the volume to 1 mL.
Preparation of Saline: Dissolve 0.9 g sodium chloride in ddH₂O and dilute to 100 mL to obtain a clear Saline solution.
Add each solvent one by one: 10% DMSO 90% (20% SBE-β-CD in Saline)
Solubility: 2 mg/mL (4.30 mM); Suspended solution; Need ultrasonic
This protocol yields a suspended solution of 2 mg/mL. Suspended solution can be used for oral and intraperitoneal injection.
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (20.0 mg/mL) to 900 μL 20% SBE-β-CD in Saline, and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C, storage for one week): 2 g SBE-β-CD powder is dissolved in 10 mL Saline, completely dissolve until clear.
Please enter the basic information of animal experiments:
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Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.
Please enter your animal formula composition:
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%DMSO +
Recommended: Keep the proportion of DMSO in working solution below 2% if your animal is weak.
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%+
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+%Tween-80 + +
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%Saline +
The co-solvents required include: DMSO, . All of co-solvents are available by MedChemExpress (MCE). , Tween 80. All of co-solvents are available by MedChemExpress (MCE).
Working solution concentration: 0.22 mg/mL
Method for preparing stock solution: mg drug dissolved in μL DMSO. Stock solution concentration: mg/mL.
1. Take μL DMSO stock solution;
2. Add μL .
μL , mix evenly;
3. Then add μL Tween 80, mix evenly;
4. Then add μL
Please ensure that the stock solution in the first step is dissolved to a clear state, and add co-solvents in sequence. You can use ultrasonic heating (ultrasonic cleaner, recommended frequency 20-40 kHz), vortexing, etc. to assist dissolution.
Pureté et documentation
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Fiche technique (286 KB)
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SDS (254 KB)
- English - EN (254 KB)
- Français - FR (254 KB)
- Deutsch - DE (254 KB)
- Norwegian - NO (254 KB)
- Español - ES (254 KB)
- Swedish - SV (254 KB)
- Italian - IT (254 KB)
- Korean - KR (254 KB)
- Portuguese - PT (254 KB)
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Instruction de manipulation (2659 KB)
Références
[1]. Lars D Engstrom, et al. MRTX1719 is an MTA-cooperative PRMT5 inhibitor that exhibits synthetic lethality in preclinical models and patients with MTAP deleted cancer. Cancer Discov. 2023 Aug 8;CD-23-0669. [Content Brief]
[2]. Christopher R Smith, et al. Fragment-Based Discovery of MRTX1719, a Synthetic Lethal Inhibitor of the PRMT5•MTA Complex for the Treatment of MTAP-Deleted Cancers. J Med Chem. 2022 Feb 10;65(3):1749-1766. [Content Brief]
Complete Stock Solution Preparation Table
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
| Optional Solvent | Concentration Solvent Mass | 1 mg | 5 mg | 10 mg | 25 mg |
|---|---|---|---|---|---|
| DMSO | 1 mM | 2.1511 mL | 10.7555 mL | 21.5109 mL | 53.7773 mL |
| 5 mM | 0.4302 mL | 2.1511 mL | 4.3022 mL | 10.7555 mL | |
| 10 mM | 0.2151 mL | 1.0755 mL | 2.1511 mL | 5.3777 mL | |
| 15 mM | 0.1434 mL | 0.7170 mL | 1.4341 mL | 3.5852 mL | |
| 20 mM | 0.1076 mL | 0.5378 mL | 1.0755 mL | 2.6889 mL | |
| 25 mM | 0.0860 mL | 0.4302 mL | 0.8604 mL | 2.1511 mL | |
| 30 mM | 0.0717 mL | 0.3585 mL | 0.7170 mL | 1.7926 mL | |
| 40 mM | 0.0538 mL | 0.2689 mL | 0.5378 mL | 1.3444 mL | |
| 50 mM | 0.0430 mL | 0.2151 mL | 0.4302 mL | 1.0755 mL | |
| 60 mM | 0.0359 mL | 0.1793 mL | 0.3585 mL | 0.8963 mL | |
| 80 mM | 0.0269 mL | 0.1344 mL | 0.2689 mL | 0.6722 mL | |
| 100 mM | 0.0215 mL | 0.1076 mL | 0.2151 mL | 0.5378 mL |
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