AZD-3759

• CAT Number: I002094
• CAS Number: 1626387-80-1
• Molecular Formula: C₂₂H₂₃ClFN₅O₃
• Molecular Weight: 459.9
• Purity: ≥95%
• Synonyms: AZD3759; (2R)-2,4-dimethyl-1-piperazinecarboxylic acid-4-[(3-chloro-2-fluorophenyl)amino]-7-methoxy-6-quinazolinyl ester
• Target: Protein Tyrosine Kinase/RTK
• Solubility: 10 mM in DMSO
• Storage: -20°C
• IC50: 7.2 nM (L858R pEGFR)
• InChI: InChI=1S/C22H23ClFN5O3/c1-13-11-28(2)7-8-29(13)22(30)32-19-9-14-17(10-18(19)31-3)25-12-26-21(14)27-16-6-4-5-15(23)20(16)24/h4-6,9-10,12-13H,7-8,11H2,1-3H3,(H,25,26,27)/t13-/m1/s1
• InChIKey: MXDSJQHFFDGFDK-CYBMUJFWSA-N
• SMILES: CN(CCN1C(=O)OC2=C(C=C3C(=C2)C(=NC=N3)NC4=C(C(=CC=C4)Cl)F)OC)C

AZD3759 (Cat No.: I002094) is another extremely effective drug with 100% intracranial permeability and far superior efficacy to erlotinib, gefitinib, alfatinib and oxitinib. It is an effective EGFR inhibitor that can penetrate the central nervous system. Acting on EGFRwt, EGFRL858R and EGFRxon 19Del, IC50 is 0.3, 0.2 and 0.2 nM respectively.

Overview of Clinical Research

Originator: AstraZeneca
Class: Amines; Antineoplastics; Piperazines; Quinazolines
Mechanism of Action: Epidermal growth factor receptor antagonists
Orphan Drug Status: No
New Molecular Entity: Yes

Reference

1: Ahn MJ, Kim DW, Cho BC, Kim SW, Lee JS, Ahn JS, Kim TM, Lin CC, Kim HR, John
T, Kao S, Goldman JW, Su WC, Natale R, Rabbie S, Harrop B, Overend P, Yang Z,
Yang JC. Activity and safety of AZD3759 in EGFR-mutant non-small-cell lung cancer
with CNS metastases (BLOOM): a phase 1, open-label, dose-escalation and
dose-expansion study. Lancet Respir Med. 2017 Nov;5(11):891-902. doi:
10.1016/S2213-2600(17)30378-8. Epub 2017 Oct 19. PubMed PMID: 29056570.

2: Planchard D. AZD3759 for CNS metastases in EGFR-mutant lung cancer. Lancet
Respir Med. 2017 Nov;5(11):841-842. doi: 10.1016/S2213-2600(17)30395-8. Epub 2017
Oct 19. PubMed PMID: 29056569.

3: Xiong S, Xue M, Mu Y, Deng Z, Sun P, Zhou R. Determination of AZD3759 in rat
plasma and brain tissue by LC-MS/MS and its application in pharmacokinetic and
brain distribution studies. J Pharm Biomed Anal. 2017 Jun 5;140:362-366. doi:
10.1016/j.jpba.2017.03.056. Epub 2017 Mar 31. PubMed PMID: 28399431.

4: Yang Z, Guo Q, Wang Y, Chen K, Zhang L, Cheng Z, Xu Y, Yin X, Bai Y, Rabbie S,
Kim DW, Ahn MJ, Yang JC, Zhang X. AZD3759, a BBB-penetrating EGFR inhibitor for
the treatment of EGFR mutant NSCLC with CNS metastases. Sci Transl Med. 2016 Dec
7;8(368):368ra172. PubMed PMID: 27928026.

5: Zeng Q, Wang J, Cheng Z, Chen K, Johnström P, Varnäs K, Li DY, Yang ZF, Zhang
X. Discovery and Evaluation of Clinical Candidate AZD3759, a Potent, Oral Active,
Central Nervous System-Penetrant, Epidermal Growth Factor Receptor Tyrosine
Kinase Inhibitor. J Med Chem. 2015 Oct 22;58(20):8200-15. doi:
10.1021/acs.jmedchem.5b01073. Epub 2015 Oct 9. PubMed PMID: 26313252.