2. JAK/STAT Signaling Protein Tyrosine Kinase/RTK MAPK/ERK Pathway Stem Cell/Wnt PI3K/Akt/mTOR
  3. EGFR p38 MAPK ERK Akt
  4. AZ14289671

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.

For research use only. We do not sell to patients.

AZ14289671

AZ14289671 Chemical Structure

CAS No. : 3101563-22-5

Size Price Stock Quantity
5 mg Get quote 5 - 7 weeks 4 - 6 weeks 6 - 8 weeks 4 - 6 weeks
10 mg Get quote 5 - 7 weeks 4 - 6 weeks 6 - 8 weeks 4 - 6 weeks
25 mg Get quote 5 - 7 weeks 4 - 6 weeks 6 - 8 weeks 4 - 6 weeks
50 mg Get quote 5 - 7 weeks 4 - 6 weeks 6 - 8 weeks 4 - 6 weeks
100 mg Get quote 5 - 7 weeks 4 - 6 weeks 6 - 8 weeks 4 - 6 weeks
200 mg   Get quote  
500 mg   Get quote  
Synthetic products have potential research and development risk.

* Please select Quantity before adding items.

This product is a controlled substance and not for sale in your territory.

Customer Review

Based on 1 publication(s) in Google Scholar

AZ14289671 Related Antibodies

Top Publications Citing Use of Products

View All EGFR Isoform Specific Products:

View All Isoforms
EGFR/ErbB1/HER1 ErbB2/HER2 ErbB3/HER3 ErbB4/HER4

View All p38 MAPK Isoform Specific Products:

View All Isoforms
p38 MAPK Akt1 p38α p38β MAPK13 p38δ p38γ

View All ERK Isoform Specific Products:

View All Isoforms
ERK ERK1 ERK2 ERK5 ERK8

View All Akt Isoform Specific Products:

View All Isoforms
Akt Akt1 Akt2 Akt3

  • Biological Activity

  • Purity & Documentation

  • References

  • Customer Review

Description

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[1].

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.

AZ14289671 Related Antibodies

Western Blot Analysis[1]

Cell Line: LXF2478ASV EGFRExon20Ins cell line
Concentration: 10, 30, 100, 300 and 1000 nM
Incubation Time: 2 h; 6 h
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.

Real Time qPCR[1]

Cell Line: LXF2478ASV EGFRExon20Ins cell line
Concentration: 30, 100, 300 and 1000 nM
Incubation Time: 6 h
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) induces dose-dependent tumor growth inhibition in the LXF2478ASV xenograft mouse model[1].
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.

Animal Model: Hsd:Athymic Nude-Foxn1nu (female; subcutaneous xenograft of LXF2478ASV patient-derived EGFR exon 20 insertion mutant cells)[1]
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)
Administration: p.o.; twice daily; 14 days; p.o.; single dose
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.
Animal Model: C.B-17/lcrHanHsd-Prkdcscid (female; subcutaneous xenograft of H2073WT EGFR wild-type cells)[1]
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)
Administration: p.o.; twice daily; 14 days; p.o.; single dose
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.
Animal Model: C.B-17/lcrHanHsd-Prkdcscid (female; subcutaneous xenograft of A431WT EGFR wild-type cells)[1]
Dosage: 50 mg/kg
Administration: p.o.; twice daily; 16 days
Result: Achieved 86% TGI after 16 days of twice daily dosing.
Was well tolerated with body weight loss < 15%.
Animal Model: BALB/cNj-Foxn1nu/Gpt (female; subcutaneous xenograft of LU3075DNP patient-derived EGFR D770_N771InsPG exon 20 insertion mutant cells)[1]
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)
Administration: p.o.; twice daily; 28 days; p.o.; single dose
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.
Animal Model: BALB/cNj-Foxn1nu/Gpt (female; subcutaneous xenograft of LU0387NPH patient-derived EGFR N771_H773InsH exon 20 insertion mutant cells)[1]
Dosage: 25 mg/kg; 50 mg/kg
Administration: p.o.; twice daily; 28 days
Result: Achieved 45% TGI at 25 mg/kg and 133% TGI at 50 mg/kg after 28 days of twice daily dosing.
Molecular Weight

499.30

Formula

C23H14Cl2F2N6O
CAS No.
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
Shipping

Room temperature in continental US; may vary elsewhere.
Storage

Please store the product under the recommended conditions in the Certificate of Analysis.
Purity & Documentation
References
  • No file chosen (Maximum size is: 1024 Kb)
  • If you have published this work, please enter the PubMed ID.
  • Your name will appear on the site.

AZ14289671 Related Classifications

  • Molarity Calculator

  • Dilution Calculator

The molarity calculator equation

Mass (g) = Concentration (mol/L) × Volume (L) × Molecular Weight (g/mol)

Mass   Concentration   Volume   Molecular Weight *
= × ×

The dilution calculator equation

Concentration (start) × Volume (start) = Concentration (final) × Volume (final)

This equation is commonly abbreviated as: C1V1 = C2V2

Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
× = ×
C1   V1   C2   V2
Help & FAQs
  • Do most proteins show cross-species activity?

    Species cross-reactivity must be investigated individually for each product. Many human cytokines will produce a nice response in mouse cell lines, and many mouse proteins will show activity on human cells. Other proteins may have a lower specific activity when used in the opposite species.

Keywords:

AZ142896713101563-22-5AZ 14289671AZ-14289671EGFRp38 MAPKERKAktEpidermal growth factor receptorErbB-1HER1Extracellular signal regulated kinasesPKBProtein kinase BEGFR L858RHER2 Exon20 insertion (YVMA)non-small cell lung cancerHER2 wild-typeBLKJAK3EGFR Exon20 insertion mutantsEGFR L858R/T790MBMXEGFR Ex19delInhibitorinhibitorinhibit

Your Recently Viewed Products:

Inquiry Online

Your information is safe with us. * Required Fields.

Product Name

  

Requested Quantity *

Applicant Name *

 

Salutation

Email Address *

 

Phone Number *

Department

 

Organization Name *

City

State

Country or Region *

      

Remarks

Bulk Inquiry

Inquiry Information

Product Name:
AZ14289671
Cat. No.:
HY-183682
Quantity:
MCE Japan Authorized Agent:

Customer Review

Thank You for Your Feedback!

Request for HNMR Report

Please fill out this form to request the QC report. We will send it to your Email address shortly.

Your information is safe with us. * Required Fields.

Product Name

  

Lot #

Applicant Name *

 

Email Address *

Phone Number

 

Department *

Organization Name *

 

Country or Region *

Remarks

SAFETY DATA SHEET (SDS)

Request for HNMR Report

We have received your request and will respond to you as soon as possible.