AZD4625
Based on 1 Customer Validation
AZD4625 is an orally active, selective irreversible, covalent allosteric GTPase KRASG12C inhibitor with an IC50 of 3 nM. AZD4625 can inhibit the MAPK pathway (with decreased pCRAF, pMEK, and pERK) and the PI3K pathway (with decreased pAKT and pS6), and induce cell apoptosis. AZD4625 has no binding and inhibition of wild-type RAS or isoforms carrying non-KRASG12C mutations. AZD4625 can be used for the study of KRASG12C mutant non-small cell lung cancer.
Para uso exclusivo en investigación. No vendemos a pacientes.
- Pureza: 98.44%
- Fòrmula: C24H21ClF2N4O3
- Peso molecular:486.90
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Almacenamiento:Powder -20°C, 3 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
- Pureza y Documentación
- Referencias
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Help & FAQs
Actividad biológica
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KRAS(G12C) 3 nM (IC50) |
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Cell Line
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Type | Value | Description | References |
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| A549 | IC50 |
1.67 μM
Compound: 21; AZD4625
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Inhibition of spheroid proliferation in human A549 cells harboring KRAS G12C mutant measured after 6 days by CellTiter-Glo assay
Inhibition of spheroid proliferation in human A549 cells harboring KRAS G12C mutant measured after 6 days by CellTiter-Glo assay
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[PMID: 35471939] |
| NCI-H358 | IC50 |
0.0041 μM
Compound: 21; AZD4625
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Inhibition of spheroid proliferation in human NCI-H358 cells harboring KRAS G12C mutant measured after 6 days by CellTiter-Glo assay
Inhibition of spheroid proliferation in human NCI-H358 cells harboring KRAS G12C mutant measured after 6 days by CellTiter-Glo assay
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[PMID: 35471939] |
AZD4625 (Compound 21) inhibits p90RSK phosphorylation (IC50 = 36 nM) in KRASG12C mutant cells (NCI-H358)[1].
AZD4625 (0.01-3 μM, 0-120 h) reduces proliferation and survival of NCI-H358 cells (IC50 = 4.1 nM) driving cell-cycle arrest and apoptosis[1][2].
AZD4625 enhances the depth and duration of response when combined with the receptor tyrosine kinases (RTK) inhibitor SHP099 (HY-100388), the EGFR inhibitor Gefitinib (HY-50895) and ErbB inhibitor afatinib (HY-10261) in NCI-H358 and NCI-H1373 cells[2].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:NCI-H358
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Concentration:0.01, 0.1, 1, 3 μM
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Incubation Time:0, 24, 48, 72, 96, 120 h
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Result:Time- and concentration-dependently induced cell apoptosis.
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Cell Line:NCI-H358
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Concentration:0.1 and 1 μM
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Incubation Time:4 h
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Result:Increased the proportion of G1 phase and decreased the proportion of S phase.
AZD4625 (4-100 mg/kg, p.o., once daily for 20-25 days) continuously inhibits tumor regression in the HCI-H358 xenograft mouse model, and appears relatively resistant in the HCI-H358 model, however, when combined with Afatinib and SHP099 shows a powerful anti-tumor effect NCI-H358 and LU99 lung xenograft models[2].
AZD4625 (100 mg/kg, p.o., once daily for 7 days) significantly reduces the lung tumor burden in six KRASG12C patient-derived xenograft (PDX) mice models[2].
AZD4625 (100 mg/kg , p.o., once daily for 21 days) drives changes to the tumor immune microenvironment and that deeper and more durable responses may be achieved if combined with immune checkpoint inhibitors (ICIs) in KRASG12C syngeneic mouse model[2].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:KRASG12C MIAPaCa-2 xenograft model established in mice[1]
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Dosage:4, 20 and 100 mg/kg
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Administration:Oral administration (p.o.), once daily for 15-20 days
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Result:Significantly inhibited the growth of MIA PaCa-2 tumors at 100 mg/kg.
Showed a robust, dose-dependent decrease in the expression of DUSP6.
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Animal Model:NCI-H358, NCI-H2122, and LU99 xenograft model established in mice[2]
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Dosage:4, 20 and 100 mg/kg
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Administration:Oral administration (p.o.), once daily for 20-25 days
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Result:significantly inhibited the growth of NCI-H358 and NCI-H2122 models at 100 mg/kg.
Was well tolerated with no effects on animal body weight on chronic daily dosing.
Enhanced the anti-tumor effect with Afatinib and SHP099 in NCI-H2122, and LU99 xenograft model.
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Animal Model:PDX model established in female athymic nude-Foxn1nu mice or female BALB/cNj nude mice[2]
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Dosage:100 mg/kg
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Administration:Oral administration (p.o.), once daily for 7 days
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Result:Observed tumor growth inhibition and regression, with the lung tumor models appearing broadly more sensitive than colorectal.
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Animal Model:CT26G12C syngeneic model established in female BALB/cOla mice[2]
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Dosage:100 mg/kg
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Administration:Oral administration (p.o.), once daily for 21 days
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Result:Induced an initial regression, but 100% of the tumors recured.
Significantly prolonged survival period, with no recurrence after discontinuation of treatment combined with anti-PD-1 or anti-PD-L1.
Chemical Information
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Appearance Solid
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Peso molecular 486.90
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Fòrmula C24H21ClF2N4O3
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Color White to off-white
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SMILES
C=CC(N1C[C@H]2N(C3=C4C(OCC2)=C(Cl)[C@@]([C@@]5=C(F)C=CC=C5O)=C(F)C4=NC=N3)C[C@H]1C)=O
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Envío
Room temperature in continental US; may vary elsewhere.
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Almacenamiento
Powder -20°C 3 years In solvent -80°C 6 months -20°C 1 month
Solvente y solubilidad
DMSO : 100 mg/mL (205.38 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: ≥ 2.08 mg/mL (4.27 mM); Clear solution
This protocol yields a clear solution of ≥ 2.08 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (20.8 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: ≥ 2.08 mg/mL (4.27 mM); Clear solution
This protocol yields a clear solution of ≥ 2.08 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (20.8 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.
Pureza y Documentación
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Ficha de datos (285 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]. Kettle JG, et al. Discovery of AZD4625, a Covalent Allosteric Inhibitor of the Mutant GTPase KRASG12C. J Med Chem. 2022 May 12;65(9):6940-6952. [Content Brief]
[2]. Chakraborty A, et al. AZD4625 is a Potent and Selective Inhibitor of KRASG12C. Mol Cancer Ther. 2022 Oct 7;21(10):1535-1546. [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 |
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| DMSO | 1 mM | 2.0538 mL | 10.2690 mL | 20.5381 mL | 51.3452 mL |
| 5 mM | 0.4108 mL | 2.0538 mL | 4.1076 mL | 10.2690 mL | |
| 10 mM | 0.2054 mL | 1.0269 mL | 2.0538 mL | 5.1345 mL | |
| 15 mM | 0.1369 mL | 0.6846 mL | 1.3692 mL | 3.4230 mL | |
| 20 mM | 0.1027 mL | 0.5135 mL | 1.0269 mL | 2.5673 mL | |
| 25 mM | 0.0822 mL | 0.4108 mL | 0.8215 mL | 2.0538 mL | |
| 30 mM | 0.0685 mL | 0.3423 mL | 0.6846 mL | 1.7115 mL | |
| 40 mM | 0.0513 mL | 0.2567 mL | 0.5135 mL | 1.2836 mL | |
| 50 mM | 0.0411 mL | 0.2054 mL | 0.4108 mL | 1.0269 mL | |
| 60 mM | 0.0342 mL | 0.1712 mL | 0.3423 mL | 0.8558 mL | |
| 80 mM | 0.0257 mL | 0.1284 mL | 0.2567 mL | 0.6418 mL | |
| 100 mM | 0.0205 mL | 0.1027 mL | 0.2054 mL | 0.5135 mL |
AZD4625 Related Classifications
HY-146223 Related Classifications
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