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Chemical Structure| 1626387-80-1 Chemical Structure| 1626387-80-1

Structure of AZD3759
CAS No.: 1626387-80-1

Chemical Structure| 1626387-80-1

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AZD3759 is an inhibitor of EGFR (WT), EGFR (L858R) and EGFR (exon 19 deletion) (IC50s values are 0.3 nM, 0.2 nM and 0.2 nM, respectively).

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Product Details of AZD3759

CAS No. :1626387-80-1
Formula : C22H23ClFN5O3
M.W : 459.90
SMILES Code : O=C(N1[C@H](C)CN(C)CC1)OC2=CC3=C(NC4=CC=CC(Cl)=C4F)N=CN=C3C=C2OC
MDL No. :MFCD29058564
InChI Key :MXDSJQHFFDGFDK-CYBMUJFWSA-N
Pubchem ID :78209992

Safety of AZD3759

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302-H315-H319-H335
Precautionary Statements:P261-P305+P351+P338

Related Pathways of AZD3759

RTK
JAK-STAT

Isoform Comparison

Biological Activity

Description
Zorifertinib (AZD3759) is a highly potent, orally bioavailable EGFR inhibitor with the ability to penetrate the central nervous system. It demonstrates remarkable efficacy against EGFR mutations, exhibiting IC50 values of 0.3 nM for wild-type EGFR (EGFRwt), 0.2 nM for EGFR with the L858R mutation (EGFRL858R), and 0.2 nM for EGFR with an exon 19 deletion (EGFRexon 19Del) at ATP concentrations equivalent to Km. Zorifertinib effectively induces apoptosis in cancer cells and shows significant antitumor activity, making it a valuable candidate for research into non-small cell lung cancer (NSCLC), hepatocellular carcinoma (HCC), and potentially other malignancies[1].
Target
  • EGFR/ErbB1

    EGFR (L858R), IC50:0.2 nM

    EGFR (WT), IC50:0.3 nM

In Vitro:

Cell Line
Concentration Treated Time Description References
Rat liver hepatocytes (RLHs) 30 μM 2 hours Detection of in vitro metabolites of ZFB RSC Adv. 2022 Jul 21;12(32):20991-21003.
Rat liver microsomes (RLMs) 30 μM 90 minutes Detection of in vitro metabolites and reactive intermediates of ZFB RSC Adv. 2022 Jul 21;12(32):20991-21003.
A549 nonsmall lung carcinoma cells 28.67 ± 5.69 Evaluate the antiproliferative effects of AZD3759 and its derivative 7 on A549 cells, showing an IC50 value of 6.10 ±0.13 μM for 7. ACS Med Chem Lett. 2018 Dec 6;10(1):22-26.
C6-LUC cells 1, 2, 4 μM 24 hours To evaluate the effect of AZD3759 on the cell cycle of C6-LUC cells, the results showed that AZD3759 significantly increased the proportion of cells in the G0/G1 phase. Bioengineered. 2021 Dec;12(1):8679-8689.
U87 cells 1, 2, 4 μM 10-14 days To evaluate the inhibitory effect of AZD3759 on the proliferation of U87 cells, the results showed that AZD3759 significantly reduced the survival fraction of U87 cells in a dose-dependent manner. Bioengineered. 2021 Dec;12(1):8679-8689.
C6 cells 1, 2, 4 μM 10-14 days To evaluate the inhibitory effect of AZD3759 on the proliferation of C6 cells, the results showed that AZD3759 significantly reduced the survival fraction of C6 cells in a dose-dependent manner. Bioengineered. 2021 Dec;12(1):8679-8689.
Primary mouse cortical neurons 0.63 nM and 8.4 nM 4 hours To evaluate the effect of AZD3759 on α-syn-PFFs uptake, results showed AZD3759 reduced α-syn-PFFs uptake Neurotherapeutics. 2021 Apr;18(2):979-997.
H3255 cells 500 nM 30 minutes Evaluate the effect of AZD3759 on the sensitivity of NSCLC cells to radiation, results showed AZD3759 significantly enhanced RA-induced apoptosis and DNA damage Bioengineered. 2022 Jan;13(1):331-344.
PC-9 cells 500 nM 30 minutes Evaluate the effect of AZD3759 on the sensitivity of NSCLC cells to radiation, results showed AZD3759 significantly enhanced RA-induced apoptosis and DNA damage Bioengineered. 2022 Jan;13(1):331-344.

In Vivo:

Species
Animal Model
Administration Dosage Frequency Description References
Mice Traumatic brain injury (TBI) model Oral 15 mg/kg Daily administration for 14 days AZD3759 promoted the recovery of body weight and neurological function in TBI mice, reduced astrocyte activation and EGFR expression, decreased chondroitin sulfate proteoglycans deposition, and upregulated GAP43 levels in the cortex. Drug Des Devel Ther. 2024 Apr 16;18:1175-1188
Sprague Dawley rats Metabolic cages Oral gavage 10 mg/kg Once daily for 120 hours Detection of in vivo metabolites of ZFB RSC Adv. 2022 Jul 21;12(32):20991-21003.
ICR mice C6-LUC xenograft model Oral 15, 30, 60 mg/kg Once daily for 3 weeks To evaluate the anti-tumor effect of AZD3759 on the C6-LUC xenograft model, the results showed that AZD3759 significantly inhibited tumor growth in a dose-dependent manner and was superior to osimertinib. Bioengineered. 2021 Dec;12(1):8679-8689.
C57BL6/C3H F1 mice Α-syn propagation mouse model Oral gavage 15 mg/kg/day Once daily for 21 days To evaluate the effect of AZD3759 on α-syn pathology, results showed AZD3759 reduced pSyn pathology Neurotherapeutics. 2021 Apr;18(2):979-997.
Nude mice PC-9-LUC brain metastasis model Oral 15 mg/kg/day Once daily for 3 weeks Evaluate the effect of AZD3759 on RA's inhibition of PC-9 cell brain metastasis, results showed AZD3759 significantly enhanced the antitumor effects of RA Bioengineered. 2022 Jan;13(1):331-344.

Clinical Trial:

NCT Number Conditions Phases Recruitment Completion Date Locations
NCT03360929 Non Small Cell Lung Cancer PHASE1|PHASE2 COMPLETED 2020-11-13 Guangdong General Hospital, Gu... More >>angzhou, Guangdong, 510080, China|0004, Wuhan, Hubei, China|0002, Changsha, Hunan, China|0003, Hangzhou, Zhejiang, China Less <<

Protocol

Bio Calculators
Preparing Stock Solutions 1mg 5mg 10mg

1 mM

5 mM

10 mM

2.17mL

0.43mL

0.22mL

10.87mL

2.17mL

1.09mL

21.74mL

4.35mL

2.17mL

References

 

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