AZ14289671
Based on 1 Customer Validation
AZ14289671 is an orally active, blood-brain barrier-penetrant tyrosine kinase (tyrosine kinase) inhibitor (TKI) that specifically targets non-small cell lung cancer (NSCLC) harboring EGFR exon 20 insertion mutations (EGFRExon20Ins), while largely sparing wild-type EGFR to reduce off-target toxicities such as rash and diarrhea. AZ14289671 inhibits the downstream MAPK/ERK/AKT pathway, suppressing tumor cell proliferation, survival and migration. AZ14289671 can be used for NSCLC research.
Nos produits utilisent uniquement pour la recherche. Nous ne vendons pas aux patients.
- Pureté : 99.77%
- CAS No.: 3101563-22-5
- Formule: C23H14Cl2F2N6O
- Masse moléculaire:499.30
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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
- Protocole
- Pureté et documentation
- Références
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Help & FAQs
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Activité biologique
Description
IC50 & Target
[1]|
EGFR exon 20 insertion |
In Vitro
AZ14289671 (1 μM) exhibits high kinome selectivity, with only a small subset of non-EGFR family kinases showing inhibition rates exceeding 50%[1].
AZ14289671 (2 h) potently inhibits EGFR phosphorylation in EGFRExon20Ins cell lines (mean IC50 = 17-41 nM), with significantly reduced activity in EGFRWT cell lines (mean IC50 = 480-832 nM), exhibiting high mutant selectivity[1].
AZ14289671 (2 h) potently inhibits ERK phosphorylation in LXF2478ASV EGFR Exon20Ins cells, with a mean IC50 of 32 nM[1].
AZ14289671 (10-1000 nmol/L; 2 h, 6 h) potently inhibits MAPK pathway signaling (including phosphorylation of ERK, AKT and S6) in LXF2478ASV EGFRExon20Ins cells after 2 h and 6 h of treatment[1].
AZ14289671 (30-1000 nM; 6 h) dose-dependently inhibits the gene expression of the MAPK pathway in LXF2478ASV EGFR exon 20 insertion mutant cells[1].
AZ14289671 (2 h) potently inhibits EGFR phosphorylation in EGFRExon20Ins/T790M, EGFRL858R, EGFRL858R/T790M and EGFREx19del cell lines (mean IC50 = 7-45 nM), and suppresses HER2 phosphorylation in BT-474HER2WT and H2170HER2YVMA cells with mean IC50 values of 75 nM and 125 nM, respectively[1].
AZ14289671 (1 μM; 2 h) exhibits low propensity as an efflux transporter substrate, with an efflux ratio of 1.5 in MDCKII-MDR1-BCRP cells and 4.7 in MDCKI-MDR1 cells[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:LXF2478ASV EGFRExon20Ins cell line
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Concentration:10, 30, 100, 300 and 1000 nM
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Incubation Time:2 h; 6 h
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Result:Inhibited downstream EGFR signaling pathways after both 2 and 6 h of treatment, with the most robust inhibition observed for ERK phosphorylation.
Showed evident inhibition of AKT and S6 phosphorylation in a dose-dependent manner.
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Cell Line:LXF2478ASV EGFRExon20Ins cell line
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Concentration:30, 100, 300 and 1000 nM
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Incubation Time:6 h
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Result:Caused significant, dose-dependent inhibition of MAPK pathway gene expression at 30 nM and above.
Observed significant downregulation for CCND1, DUSP6, EPHA2, EPHA4, ETV5, and SPRY4, correlating with immunoblotting data showing reduced MAPK signaling.
In Vivo
AZ14289671 (6.25-50 mg/kg; p.o.; twice daily; for 14 consecutive days) exhibits significantly lower tumor growth inhibitory activity (maximum TGI of 62%) and EGFR phosphorylation inhibition in the H2073WT xenograft mouse model[1].
AZ14289671 (50 mg/kg; p.o.; twice daily; for 16 consecutive days) induces 86% TGI in the A431WT xenograft mouse model[1].
AZ14289671 (6.25-50 mg/kg; p.o.; twice daily; for 28 consecutive days) induces dose-dependent tumor growth inhibition in the LU3075DNP xenograft mouse model[1].
AZ14289671 (25-50 mg/kg; p.o.; twice daily; for 28 consecutive days) induces dose-dependent tumor growth inhibition in the LU0387NPH xenograft mouse model[1].
AZ14289671 (2 μmol/kg/h; intravenous injection; continuous infusion; 4 h) crosses the blood-brain barrier of healthy rats, with a Kpuu value of 0.17[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:Hsd:Athymic Nude-Foxn1nu (female; subcutaneous xenograft of LXF2478ASV patient-derived EGFR exon 20 insertion mutant cells)[1]
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Dosage:6.25 mg/kg (twice daily dosing); 12.5 mg/kg (twice daily dosing; single dose); 25 mg/kg (twice daily dosing; single dose); 50 mg/kg (twice daily dosing; single dose)
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Administration:p.o.; twice daily; 14 days; p.o.; single dose
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Result:Achieved 71% TGI at 6.25 mg/kg, 81% TGI at 12.5 mg/kg, 112% TGI at 25 mg/kg, and 121% TGI after 14 days of twice daily dosing.
Significantly reduced EGFR phosphorylation at 1 and 6 hours post single dose across all dose levels, with >90% reduction observed at 6 hours post 50 mg/kg single dose.
Showed recovery of EGFR phosphorylation at 16 and 24 hours post single dose.
Maintained free plasma concentrations exceeding the IC90 for approximately 6 hours post single dose.
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Animal Model:C.B-17/lcrHanHsd-Prkdcscid (female; subcutaneous xenograft of H2073WT EGFR wild-type cells)[1]
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Dosage:6.25 mg/kg (twice daily dosing); 12.5 mg/kg (twice daily dosing; single dose); 25 mg/kg (twice daily dosing; single dose); 50 mg/kg (twice daily dosing; single dose)
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Administration:p.o.; twice daily; 14 days; p.o.; single dose
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Result:Achieved 47% TGI at 6.25 mg/kg, 53% TGI at 12.5 mg/kg, 55% TGI at 25 mg/kg, and 62% TGI after 14 days of twice daily dosing.
Induced markedly lower EGFR phosphorylation inhibition than in mutant models, with 50 mg/kg inducing ~50% inhibition at 6 hours post single dose.
Failed to reach free plasma concentrations exceeding the IC50 at any dose level post single dose.
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Animal Model:C.B-17/lcrHanHsd-Prkdcscid (female; subcutaneous xenograft of A431WT EGFR wild-type cells)[1]
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Dosage:50 mg/kg
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Administration:p.o.; twice daily; 16 days
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Result:Achieved 86% TGI after 16 days of twice daily dosing.
Was well tolerated with body weight loss < 15%.
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Animal Model:BALB/cNj-Foxn1nu/Gpt (female; subcutaneous xenograft of LU3075DNP patient-derived EGFR D770_N771InsPG exon 20 insertion mutant cells)[1]
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Dosage:6.25 mg/kg (twice daily dosing); 12.5 mg/kg (twice daily dosing; single dose); 25 mg/kg (twice daily dosing; single dose); 50 mg/kg (twice daily dosing; single dose)
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Administration:p.o.; twice daily; 28 days; p.o.; single dose
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Result:Achieved 27% TGI at 6.25 mg/kg, 81% TGI at 12.5 mg/kg, 159% TGI at 25 mg/kg, and 169% TGI after 28 days of twice daily dosing.
Significantly inhibited EGFR phosphorylation at all dose levels post single dose, with > 75% inhibition observed at 1 and 6 hours post 25 mg/kg and 50 mg/kg single doses.
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Animal Model:BALB/cNj-Foxn1nu/Gpt (female; subcutaneous xenograft of LU0387NPH patient-derived EGFR N771_H773InsH exon 20 insertion mutant cells)[1]
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Dosage:25 mg/kg; 50 mg/kg
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Administration:p.o.; twice daily; 28 days
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Result:Achieved 45% TGI at 25 mg/kg and 133% TGI at 50 mg/kg after 28 days of twice daily dosing.
- BrdU Incorporation Assay
- Cell migration
- Somatic Cell Culture
- CFSE Dye Dilution Proliferation Assay
- Dye-dilution cell tracking and proliferation staining
- CCK-8/WST-8 Cell Proliferation Assay
- Protocol for Cell Cycle
- Cell Counting-Based Growth Curve Assay
- Colony Formation (Clonogenic) Assay
- Cell Viability Determination by MTT Colorimetric Assay
- EdU Incorporation Assay (Click Chemistry-Based DNA Synthesis Measurement)
- Ki-67 Immunostaining Proliferation Assay
- PCNA Immunodetection Proliferation Assay
- Protocol for Cell Counting and Cell Density Analysis
- MTT Cell Proliferation Assay
Chemical Information
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CAS No. 3101563-22-5
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Appearance Solid
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Masse moléculaire 499.30
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Formule C23H14Cl2F2N6O
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Color White to off-white
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SMILES
O=C(N1CC2=C(C1)N(C3=CC=NC=N3)C(C4=C(F)C=C(F)C(C5=C(Cl)N=CC(Cl)=C5)=C4)=N2)C=C
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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
Solvant et solubilité
In Vitro:
DMSO : 12.5 mg/mL (25.04 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: ≥ 1.25 mg/mL (2.50 mM); Clear solution
This protocol yields a clear solution of ≥ 1.25 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (12.5 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: ≥ 1.25 mg/mL (2.50 mM); Clear solution
This protocol yields a clear solution of ≥ 1.25 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (12.5 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.
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.
Pureté et documentation
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Fiche technique (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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Instruction de manipulation (2659 KB)
Références
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 | 2.0028 mL | 10.0140 mL | 20.0280 mL | 50.0701 mL |
| 5 mM | 0.4006 mL | 2.0028 mL | 4.0056 mL | 10.0140 mL | |
| 10 mM | 0.2003 mL | 1.0014 mL | 2.0028 mL | 5.0070 mL | |
| 15 mM | 0.1335 mL | 0.6676 mL | 1.3352 mL | 3.3380 mL | |
| 20 mM | 0.1001 mL | 0.5007 mL | 1.0014 mL | 2.5035 mL | |
| 25 mM | 0.0801 mL | 0.4006 mL | 0.8011 mL | 2.0028 mL |
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