AZ-PRMT5i-1
Based on 1 Customer Validation
AZ-PRMT5i-1 is an orally active PRMT5 inhibitor. AZ-PRMT5i-1 acts as an MTA-cooperative inhibitor that binds to PRMT5-MTA and blocks PRMT5-mediated arginine methylation. AZ-PRMT5i-1 shows selectivity against lysine/arginine methyltransferases and a broad panel of biological targets, and selectively targets MTAP-deficient tumors, demonstrating dose-dependent tumor SDMA inhibition and tumor growth inhibition in MTAP-deficient xenograft and PDX gastric/lung cancer models without obvious toxicity. AZ-PRMT5i-1 can be used for research on MTAP-deficient cancers.
Para uso exclusivo en investigación. No vendemos a pacientes.
- Pureza : 98.00%
- No. CAS: 2918814-96-5
- Fòrmula: C26H20F3N5O2
- Peso molecular:491.46
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Almacenamiento: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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Actividad biológica
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Chemical Information
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Solvente y solubilidad
- Protocolo
- Pureza y Documentación
- Referencias
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Help & FAQs
Ver todos los productos específicos de isoformas Histone Methyltransferase
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Actividad biológica
Descripciòn
Cellular Effect
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Cell Line
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Type | Value | Description | References |
|---|---|---|---|---|
| HCT116 MTAP-de | IC50 |
0.0055 μM
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Inhibition of SDMA in HCT-116 MTAP KO cells incubated 48 hrs.
Inhibition of SDMA in HCT-116 MTAP KO cells incubated 48 hrs.
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39080842 |
| Lu-99 cell line | IC50 |
124 nM
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Antiproliferative activity against MTAP-null human LU99 lung cancer cells.
Antiproliferative activity against MTAP-null human LU99 lung cancer cells.
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39080842 |
| HCT116 MTAP-de | IC50 |
5.5 nM
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Inhibition of symmetric dimethylarginine (SDMA) in human HCT116 MTAP KO cells by cell-based SDMA assay after 48 hrs incubation.
Inhibition of symmetric dimethylarginine (SDMA) in human HCT116 MTAP KO cells by cell-based SDMA assay after 48 hrs incubation.
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42172174 |
| HCT116 MTAP-de | IC50 |
5.4 nM
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Inhibition of PRMT5-mediated SDMA in HCT116 MTAP knockout cells by cell SDMA assay.
Inhibition of PRMT5-mediated SDMA in HCT116 MTAP knockout cells by cell SDMA assay.
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1538-7445.AM2023-3088 |
| HCT-116 | IC50 |
290 nM
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Inhibition of PRMT5-mediated SDMA in HCT116 MTAP wild-type cells by cell SDMA assay.
Inhibition of PRMT5-mediated SDMA in HCT116 MTAP wild-type cells by cell SDMA assay.
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1538-7445.AM2023-3088 |
In Vitro
AZ-PRMT5i-1 exhibits an in vitro antiproliferative IC50 of 124 nM in MTAP-deleted LU99 lung cancer cells[1].
AZ-PRMT5i-1 selectively inhibits SDMA in MTAP-deleted tumors, with a 54-fold advantage over MTAP wild-type, and maintains differential activity in proliferation assays across isogenic MTAP cell lines and a panel of 300 cancer cell lines[4].
AZ-PRMT5i-1 is highly selective for PRMT5 and PRMT5 C449S among 37 methyltransferases[1].
AZ-PRMT5i-1 inhibits only BZD/TSPO among 86 targets, with a Ki of 0.61 μM[1].
AZ-PRMT5i-1 (0.0055 μM; 48 h) inhibits SDMA in HCT-116 MTAP KO cells with an IC50 of 5.5 nM and exhibits 55-fold MTA cooperativity compared with HCT-116 MTAP WT cells[1].
AZ-PRMT5i-1 shows low intrinsic clearance in human hepatocytes, human liver microsomes, and rat hepatocytes[2].
AZ-PRMT5i-1 (24 h, 25°C, pH 7.4) has low aqueous solubility at pH 7.4, which is 8 μM[2].
AZ-PRMT5i-1 has a free fraction of 11.8% in 10% human plasma[2].
AZ-PRMT5i-1 co-crystallizes with the PRMT5-MTA complex (PDB 9EYX) and exhibits canonical head group and backbone contacts[2].
AZ-PRMT5i-1 is a potent PRMT5 inhibitor with an SDMA IC50 of 5.4 nM in HCT116 MTAP KO cells and 54-fold selectivity over HCT116 MTAP WT cells[3].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
Parmacokinetics
In Vivo
AZ-PRMT5i-1 (1-50 mg/kg; p.o.; BID; 21 days) induces tumor regression and near-complete tumor SDMA inhibition at 50 mg/kg BID in the MTAP-deleted GA2254 gastric cancer PDX model, with lower doses producing 33% growth inhibition[1].
AZ-PRMT5i-1 exhibits single-agent antitumor activity in MTAP-deficient gastric cancer and lung cancer xenograft and PDX models[4].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:MTAP-deleted LU99 lung cancer xenograft model[1]
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Dosage:100 mg/kg
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Administration:p.o.; BID; 21 days
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Result:Demonstrated 71% tumor growth inhibition using the 100 mg/kg BID oral dosing regime.
Inhibited tumor SDMA levels by 95% at 100 mg/kg BID.
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Animal Model:MTAP-deleted GA2254 gastric cancer PDX model[1]
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Dosage:1 mg/kg; 10 mg/kg; 50 mg/kg
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Administration:p.o.; BID; 21 days
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Result:50 mg/kg BID induced tumor regression and inhibited tumor SDMA by 97%.
10 mg/kg BID reduced tumor SDMA levels by 93% and led to growth inhibition of 33%.
In the supplied image, 10 mg/kg BID showed 33% TGI and 50 mg/kg BID showed 50% regression.
Chemical Information
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No. CAS 2918814-96-5
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Appearance Solid
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Peso molecular 491.46
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Fòrmula C26H20F3N5O2
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Color White to off-white
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SMILES
O=C1N(CC2=CC3=C(C=C(F)C(N)=N3)N2)[C@@]4(CCN(CC5=CC=C(F)C=C5)C4=O)C6=C1C=C(F)C=C6
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Envío
Room temperature in continental US; may vary elsewhere.
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Almacenamiento
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month
Solvente y solubilidad
In Vitro:
DMSO : 100 mg/mL (203.48 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)
In Vivo:
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: ≥ 5 mg/mL (10.17 mM); Clear solution
This protocol yields a clear solution of ≥ 5 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (50.0 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.
In Vivo Dissolution Calculator
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.
Pureza y Documentación
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Ficha de datos (282 KB)
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SDS (252 KB)
- English - EN (252 KB)
- Français - FR (252 KB)
- Deutsch - DE (252 KB)
- Norwegian - NO (252 KB)
- Español - ES (252 KB)
- Swedish - SV (252 KB)
- Italian - IT (252 KB)
- Korean - KR (252 KB)
- Portuguese - PT (252 KB)
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Instrucciones de manejo (2659 KB)
Referencias
[1]. Smith JM, et al. Discovery and Efficacy of AZ-PRMT5i-1, a Novel PRMT5 Inhibitor with High MTA Cooperativity. Journal of medicinal chemistry. 2024 Aug 22;67(16):13604-13638. [Content Brief]
[2]. Smith JM, et al. Use of Human Dose Prediction Metrics to Enable Discovery of AZD3470, an MTA-Cooperative PRMT5 Inhibitor in Clinical Evaluation. Journal of medicinal chemistry. 2026 Jun 11;69(11):13725-13752. [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 | 2.0348 mL | 10.1738 mL | 20.3475 mL | 50.8688 mL |
| 5 mM | 0.4070 mL | 2.0348 mL | 4.0695 mL | 10.1738 mL | |
| 10 mM | 0.2035 mL | 1.0174 mL | 2.0348 mL | 5.0869 mL | |
| 15 mM | 0.1357 mL | 0.6783 mL | 1.3565 mL | 3.3913 mL | |
| 20 mM | 0.1017 mL | 0.5087 mL | 1.0174 mL | 2.5434 mL | |
| 25 mM | 0.0814 mL | 0.4070 mL | 0.8139 mL | 2.0348 mL | |
| 30 mM | 0.0678 mL | 0.3391 mL | 0.6783 mL | 1.6956 mL | |
| 40 mM | 0.0509 mL | 0.2543 mL | 0.5087 mL | 1.2717 mL | |
| 50 mM | 0.0407 mL | 0.2035 mL | 0.4070 mL | 1.0174 mL | |
| 60 mM | 0.0339 mL | 0.1696 mL | 0.3391 mL | 0.8478 mL | |
| 80 mM | 0.0254 mL | 0.1272 mL | 0.2543 mL | 0.6359 mL | |
| 100 mM | 0.0203 mL | 0.1017 mL | 0.2035 mL | 0.5087 mL |
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