AZD3759 is also known as zorifertinib. It is an orally available inhibitor of the epidermal growth factor receptor (EGFR), with potential antineoplastic activity. Upon oral administration, AZD3759 binds to and inhibits the activity of EGFR as well as certain mutant forms of EGFR. This prevents EGFR-mediated signaling, and may lead to both induction of cell death and inhibition of tumor growth in EGFR-overexpressing cells. EGFR, a receptor tyrosine kinase mutated in many tumor cell types, plays a key role in tumor cell proliferation and tumor vascularization.
Chemical Formula: C22H23ClFN5O3
Exact Mass: 459.14735
Molecular Weight: 459.91
Elemental Analysis: C, 57.46; H, 5.04; Cl, 7.71; F, 4.13; N, 15.23; O, 10.44
Appearance: white to off-white solid powder
Purity: >98% (or refer to the Certificate of Analysis)
Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility: Soluble in DMSO, not in water
Shelf Life: >2 years if stored properly
Drug Formulation: This drug may be formulated in DMSO
Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code: 2934.99.9001
At 2 mM of ATP concentrations, the IC50s are 102, 7.6, and 2.4 nM for EGFRwt, EGFRL858R, and EGFRexon 19Del, respectively. Zorifertinib (AZD3759) also inhibits pEGFR in H838wt, H3255L858R, and PC-9exon 19Del with IC50 of 64.5, 7.2, and 7.4 nM, respectively. In cellular phosphorylation studies, Zorifertinib also demonstrates 9-fold inhibition selectivity in EGFR-activating mutant cell lines over EGFR wild-type cell lines (H838 cell line).
Following oral dosing in rats at 2 mg/kg, absorption of Zorifertinib (AZD3759) is rapid with blood Cmax of 0.58 μM achieved at 1.0 h. Subsequently, blood concentrations of Zorifertinib decline monoexponentially with a mean elimination half-life of 4.3 h, which is close to the same parameter obtained from intravenous dosing of 4.1 h. The bioavailability following an oral dose in rats is 91%. Blood pharmacokinetic parameters of Zorifertinib in male dogs are determined following both a single dose intravenous infusion and oral administration. Following the IV dose in dogs, Zorifertinib blood clearance is determined as 14 mL/min per kg, and the volume of distribution is 6.4 L/kg. Its elimination half-life is 6.2 h. Absorption of Zorifertinib is rapid with blood Cmax (698 nM) occurring between 0.5 and 1.5 h. The oral bioavailability of Zorifertinib is excellent at 90%. Zorifertinib demonstrated significant dose-dependent antitumor efficacy (78% tumor growth inhibition at 7.5 mg/kg qd and tumor regression at 15 mg/kg qd, respectively, 4 weeks after treatment) with <20% body weight loss, whereas erlotinib had a limited effect in this model. At the end of the study, brain tissues are collected for histological assessment. Significantly decreased tumor area is observed by Zorifertinib treatment at the doses of 7.5 and 15 mg/kg. In addition, modulation of pEGFR is detected by a single dose of Zorifertinib at 15 mg/kg 1h after dosing, which confirmed target engagement by Zorifertinib.
Tan CS, Cho BC, Soo RA. Next-generation epidermal growth factor receptor tyrosine kinase inhibitors in epidermal growth factor receptor -mutant non-small cell lung cancer. Lung Cancer. 2016 Mar;93:59-68. doi: 10.1016/j.lungcan.2016.01.003. Epub 2016 Jan 8. Review. PubMed PMID: 26898616.
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. (Last updated: 4/20/2016).
Products are for research use only. Not for human use.
Payment & Security
Your payment information is processed securely. We do not store credit card details nor have access to your credit card information.