AZ5104

Cas：1421373-98-9

Product Information：

AZ5104 is a demethylated metabolite of AZD-9291. AZ-5104 was identified to exhibit 5-fold potency compared to AZD-9291, which is currently in clinical trial.

Chemical Formula: C27H31N7O2

Exact Mass: 485.25392

Molecular Weight: 485.58

Elemental Analysis: C, 66.78; H, 6.43; N, 20.19; O, 6.59

Synonym: 

AZ5104

AZ-5104

AZ 5104

Demethylated AZ9291

metabolite of AZD9291

Chemical Name:

N-(5-((4-(1H-indol-3-yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acrylamide

InChi Key:

IQNVEOMHJHBNHC-UHFFFAOYSA-N

InChi Code: 

InChI=1S/C27H31N7O2/c1-6-26(35)30-22-15-23(25(36-5)16-24(22)34(4)14-13-33(2)3)32-27-28-12-11-21(31-27)19-17-29-20-10-8-7-9-18(19)20/h6-12,15-17,29H,1,13-14H2,2-5H3,(H,30,35)(H,28,31,32)

Smiles Code:

C=CC(NC1=CC(NC2=NC=CC(C3=CNC4=C3C=CC=C4)=N2)=C(OC)C=C1N(CCN(C)C)C)=O.

Technical Data：

Appearance: 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

In Vitro：

AZ-5104 inhibits EGFR phosphorylation with IC50s of 2, 1, 2, 53, and 33 nM in H1975 (EGFRL858R/T790M), PC-9VanR (EGFRExon 19 deletion/T790M), PC-9 (EGFRExon 19 deletion), H2073 (WT), and LOVO (WT), respectively. AZ5104 exhibits a reduced selectivity margin against wild-type EGFR when compared to AZD9291. AZ5104 display minimal off-target activity against other non-HER family kinases, but has the potential to target both HER2 and HER4 kinase activity.

In Vivo：

The metabolite, AZ5104 (5 mg/kg/day), is effective in shrinking tumors in both C/L858R and C/L+T mice.

References：

1. Liao BC, Lin CC, Yang JC. Second and third-generation epidermal growth factor receptor tyrosine kinase inhibitors in advanced nonsmall cell lung cancer. Curr Opin Oncol. 2015 Jan 21. [Epub ahead of print] PubMed PMID: 25611025.

2. Stinchcombe TE. Recent advances in the treatment of non-small cell and small cell lung cancer. F1000Prime Rep. 2014 Dec 1;6:117. doi: 10.12703/P6-117. eCollection 2014. Review. PubMed PMID: 25580271; PubMed Central PMCID: PMC4251418.

3. Steuer CE, Khuri FR, Ramalingam SS. The next generation of epidermal growth factor receptor tyrosine kinase inhibitors in the treatment of lung cancer. Cancer. 2014 Dec 17. doi: 10.1002/cncr.29139. [Epub ahead of print] PubMed PMID: 25521095.

4. Meador CB, Jin H, de Stanchina E, Nebhan CA, Pirazzoli V, Wang L, Lu P, Vuong H, Hutchinson KE, Jia P, Chen X, Eisenberg R, Ladanyi M, Politi K, Zhao Z, Lovly CM, Cross DA, Pao W. Optimizing the Sequence of Anti-EGFR-Targeted Therapy in EGFR-Mutant Lung Cancer. Mol Cancer Ther. 2014 Dec 4. [Epub ahead of print] PubMed PMID: 25477325.

5. Nguyen KS, Neal JW, Wakelee H. Review of the current targeted therapies for non-small-cell lung cancer. World J Clin Oncol. 2014 Oct 10;5(4):576-87. doi: 10.5306/wjco.v5.i4.576. Review. PubMed PMID: 25302162; PubMed Central PMCID: PMC4129523.

Products are for research use only. Not for human use.