AZ5104 | AZ-51-4 | AZ9291 | CAS#1421373-98-9 | EGFR inhibitor

AZ5104
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WARNING: This product is for research use only, not for human or veterinary use.

MedKoo CAT#: 206180

CAS#: 1421373-98-9

Description: 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. AZ5104 is a potent EGFR inhibitor with IC50 of <1 nM, 6 nM, 1 nM, and 25 nM for EGFR (L858R/T790M), EGFR (L858R), EGFR (L861Q), and EGFR (wildtype), respectively.

Chemical Structure

AZ5104

CAS# 1421373-98-9

Instruction

Theoretical Analysis

MedKoo Cat#: 206180
Name: AZ5104
CAS#: 1421373-98-9
Chemical Formula: C27H31N7O2
Exact Mass: 485.25
Molecular Weight: 485.580
Elemental Analysis: C, 66.78; H, 6.43; N, 20.19; O, 6.59

Price and Availability

Size	Price	Availability
25mg	USD 250	2 Weeks
50mg	USD 450	2 Weeks
100mg	USD 750	2 Weeks
200mg	USD 1250	2 Weeks
500mg	USD 2650	2 Weeks
1g	USD 3850	2 Weeks
2g	USD 6450	2 Weeks
Bulk inquiry Welcome, Customer: Please do not inquire quote if your intended use is for a patient since our products are for research use and for chemical synthesis use, not for human use . For in-stock products, we listed price in the web page. You may inquire prices for which sizes were not listed. If no price is listed, this means the product is not in stock at the moment, which may be available via custom synthesis. For cost-effective reason, minimum order of 1g is requested (typically very expensive). The lead time is usually 2-4 months. Quote of less than 1g will not be provided. MedKoo may not offer quote for below reasons: (1) current available synthetic method appears to be extremely expensive which is obviously not affordable to most customers; (2) Key raw material to make the product is temporally not available; (3) DEA controlled substances; (4) the product is under patent protection in customer’s country.

Synonym: AZ5104; AZ-5104; AZ 5104. Demethylated AZ9291. metabolite of AZD9291

IUPAC/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.

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

More Info:

Instruction:

View handling instruction

Biological target:
In vitro activity:
In vivo activity:

Preparing Stock Solutions

The following data is based on the product molecular weight 485.58 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Concentration / Solvent Volume / Mass	1 mg	5 mg	10 mg
1 mM	1.15 mL	5.76 mL	11.51 mL
5 mM	0.23 mL	1.15 mL	2.3 mL
10 mM	0.12 mL	0.58 mL	1.15 mL
50 mM	0.02 mL	0.12 mL	0.23 mL

Formulation protocol:
In vitro protocol:
In vivo protocol:

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1: Fan F, Zhou M, Ye X, Mo Z, Ma Y, Luo L, Liang X, Liu H, Weng Y, Lin M, Liu X, Cai X, Qian C. BEBT-109, a pan-mutant-selective EGFR inhibitor with potent antitumor activity in EGFR-mutant non-small cell lung cancer. Transl Oncol. 2021 Feb;14(2):100961. doi: 10.1016/j.tranon.2020.100961. Epub 2020 Dec 13. PMID: 33321427; PMCID: PMC7745057.

2: Karaś K, Sałkowska A, Karwaciak I, Walczak-Drzewiecka A, Dastych J, Bachorz RA, Ratajewski M. The Dichotomous Nature of AZ5104 (an EGFR Inhibitor) Towards RORγ and RORγT. Int J Mol Sci. 2019 Nov 17;20(22):5780. doi: 10.3390/ijms20225780. PMID: 31744223; PMCID: PMC6887705.

3: Rood JJM, van Haren MJ, Beijnen JH, Sparidans RW. Bioanalysis of EGFRm inhibitor osimertinib, and its glutathione cycle- and desmethyl metabolites by liquid chromatography-tandem mass spectrometry. J Pharm Biomed Anal. 2020 Jan 5;177:112871. doi: 10.1016/j.jpba.2019.112871. Epub 2019 Sep 10. PMID: 31539712.

4: van Hoppe S, Jamalpoor A, Rood JJM, Wagenaar E, Sparidans RW, Beijnen JH, Schinkel AH. Brain accumulation of osimertinib and its active metabolite AZ5104 is restricted by ABCB1 (P-glycoprotein) and ABCG2 (breast cancer resistance protein). Pharmacol Res. 2019 Aug;146:104297. doi: 10.1016/j.phrs.2019.104297. Epub 2019 Jun 5. PMID: 31175939.

5: Koga T, Kobayashi Y, Tomizawa K, Suda K, Kosaka T, Sesumi Y, Fujino T, Nishino M, Ohara S, Chiba M, Shimoji M, Takemoto T, Suzuki M, Jänne PA, Mitsudomi T. Activity of a novel HER2 inhibitor, poziotinib, for HER2 exon 20 mutations in lung cancer and mechanism of acquired resistance: An in vitro study. Lung Cancer. 2018 Dec;126:72-79. doi: 10.1016/j.lungcan.2018.10.019. Epub 2018 Oct 17. PMID: 30527195.

6: Zhou P, Chen G, Gao M, Wu J. Design, synthesis and evaluation of the osimertinib analogue (C-005) as potent EGFR inhibitor against NSCLC. Bioorg Med Chem. 2018 Dec 15;26(23-24):6135-6145. doi: 10.1016/j.bmc.2018.10.018. Epub 2018 Oct 21. PMID: 30442506.

7: Zheng X, Wang W, Zhang Y, Ma Y, Zhao H, Hu P, Jiang J. Development and validation of a UPLC-MS/MS method for quantification of osimertinib (AZD9291) and its metabolite AZ5104 in human plasma. Biomed Chromatogr. 2018 Dec;32(12):e4365. doi: 10.1002/bmc.4365. Epub 2018 Sep 12. PMID: 30119142.

8: Vishwanathan K, So K, Thomas K, Bramley A, English S, Collier J. Absolute Bioavailability of Osimertinib in Healthy Adults. Clin Pharmacol Drug Dev. 2019 Feb;8(2):198-207. doi: 10.1002/cpdd.467. Epub 2018 Apr 23. PMID: 29683562.

9: Floc'h N, Martin MJ, Riess JW, Orme JP, Staniszewska AD, Ménard L, Cuomo ME, O'Neill DJ, Ward RA, Finlay MRV, McKerrecher D, Cheng M, Vang DP, Burich RA, Keck JG, Gandara DR, Mack PC, Cross DAE. Antitumor Activity of Osimertinib, an Irreversible Mutant-Selective EGFR Tyrosine Kinase Inhibitor, in NSCLC Harboring EGFR Exon 20 Insertions. Mol Cancer Ther. 2018 May;17(5):885-896. doi: 10.1158/1535-7163.MCT-17-0758. Epub 2018 Feb 26. PMID: 29483211; PMCID: PMC5932243.

10: Hanker AB, Brewer MR, Sheehan JH, Koch JP, Sliwoski GR, Nagy R, Lanman R, Berger MF, Hyman DM, Solit DB, He J, Miller V, Cutler RE Jr, Lalani AS, Cross D, Lovly CM, Meiler J, Arteaga CL. An Acquired HER2T798I Gatekeeper Mutation Induces Resistance to Neratinib in a Patient with HER2 Mutant-Driven Breast Cancer. Cancer Discov. 2017 Jun;7(6):575-585. doi: 10.1158/2159-8290.CD-16-1431. Epub 2017 Mar 8. Erratum in: Cancer Discov. 2019 Feb;9(2):303. PMID: 28274957; PMCID: PMC5457707.

11: Brown K, Comisar C, Witjes H, Maringwa J, de Greef R, Vishwanathan K, Cantarini M, Cox E. Population pharmacokinetics and exposure-response of osimertinib in patients with non-small cell lung cancer. Br J Clin Pharmacol. 2017 Jun;83(6):1216-1226. doi: 10.1111/bcp.13223. Epub 2017 Feb 6. PMID: 28009438; PMCID: PMC5427226.

12: Yates JW, Ashton S, Cross D, Mellor MJ, Powell SJ, Ballard P. Irreversible Inhibition of EGFR: Modeling the Combined Pharmacokinetic-Pharmacodynamic Relationship of Osimertinib and Its Active Metabolite AZ5104. Mol Cancer Ther. 2016 Oct;15(10):2378-2387. doi: 10.1158/1535-7163.MCT-16-0142. Epub 2016 Jul 20. PMID: 27439477.

13: Dickinson PA, Cantarini MV, Collier J, Frewer P, Martin S, Pickup K, Ballard P. Metabolic Disposition of Osimertinib in Rats, Dogs, and Humans: Insights into a Drug Designed to Bind Covalently to a Cysteine Residue of Epidermal Growth Factor Receptor. Drug Metab Dispos. 2016 Aug;44(8):1201-12. doi: 10.1124/dmd.115.069203. Epub 2016 May 25. PMID: 27226351.

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