Osimertinib mesylate | AZD-9291 | CAS#1421373-66-1 | CAS#1421373-65-0 | EGFR inhibitor

MedKoo Cat#: 206426 | Name: Osimertinib mesylate

Description:

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

Osimertinib, also known as mereletinib and AZD-9291, is a third-generation EGFR inhibitor, showed promise in preclinical studies and provides hope for patients with advanced lung cancers that have become resistant to existing EGFR inhibitors. AZD9291 is highly active in preclinical models and is well tolerated in animal models. It inhibits both activating and resistant EGFR mutations while sparing the normal form of EGFR that is present in normal skin and gut cells, thereby reducing the side effects encountered with currently available medicines. Osimertinib was approved on Nov. 2015.

Chemical Structure

Osimertinib mesylate

CAS#1421373-66-1 (mesylate)

Theoretical Analysis

MedKoo Cat#: 206426

Name: Osimertinib mesylate

CAS#: 1421373-66-1 (mesylate)

Chemical Formula: C29H37N7O5S

Exact Mass: 0.0000

Molecular Weight: 595.72

Elemental Analysis: C, 58.47; H, 6.26; N, 16.46; O, 13.43; S, 5.38

Price and Availability

Size	Price	Availability
1g	USD 150.00	Ready to ship
2g	USD 250.00	Ready to ship
5g	USD 550.00	Ready to ship
10g	USD 950.00	Ready to ship
20g	USD 1,650.00	Ready to ship

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Related CAS #

1421373-65-0 (free base) 1421373-66-1 (mesylate)

Synonym

AZD-9291; AZD 9291; AZD9291; AZD-9291 mesylate; Mereletinib; Mereletinib mesylate; Osimertinib mesylate. Brand name: Tagrisso.

IUPAC/Chemical Name

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

InChi Key

FUKSNUHSJBTCFJ-UHFFFAOYSA-N

InChi Code

InChI=1S/C28H33N7O2.CH4O3S/c1-7-27(36)30-22-16-23(26(37-6)17-25(22)34(4)15-14-33(2)3)32-28-29-13-12-21(31-28)20-18-35(5)24-11-9-8-10-19(20)24;1-5(2,3)4/h7-13,16-18H,1,14-15H2,2-6H3,(H,30,36)(H,29,31,32);1H3,(H,2,3,4)

SMILES Code

CN(CCN(C)C)C1=CC(OC)=C(C=C1NC(C=C)=O)NC2=NC=CC(C3=CN(C)C4=C3C=CC=C4)=N2.OS(=O)(C)=O

Appearance

Light yellow 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

Related CAS# CAS#1421373-65-0 (Osimertinib free base); CAS#1421373-66-1 (Osimertinib mesylate salt)

Product Data

Product Data

Certificate of Analysis

View CoA: current batch, Lot#T21Z03C30

View CoA: current batch, Lot# T8Z11C15

QC Data

View QC data: current batch, Lot#T21Z03C30

View QC data: current batch, Lot#T8Z11C15

Safety Data Sheet (SDS)

View Safety Data Sheet (SDS)

Instruction

View handling instruction

Biological target:

Osimertinib mesylate (AZD-9291 mesylate) is an irreversible and mutant selective EGFR inhibitor with IC50s of 12 and 1 nM against EGFRL858R and EGFRL858R/T790M, respectively.

In vitro activity:

This study tried to construct a novel therapeutic strategy to conquer the resistance to second-and third-generation EGFR-TKIs in EGFR-positive NSCLC patients. Afatinib- and osimertinib-resistant lung adenocarcinoma cell lines were established. Exome sequencing, cDNA array and miRNA microarray were performed using the established cell lines to discover novel therapeutic targets associated with the resistance to second-and third-generation EGFR-TKIs. The third-generation EGFR-TKI, osimertinib, targets T790M and EGFR-activating mutations. MiRNA microarray analysis revealed miR-200a and miR-200b were remarkably downregulated in the osimertinib-resistant cell lines (Fig. 2a). Decreased expression of miR-200a, miR-200b and miR-200c were observed in the osimertinib-resistant cell lines by qRT-PCR CDNA microarray analysis was performed to identify the genes associated with resistance to afatinib and osimertinib using the parental and EGFR-TKIs-resistant NSCLC cells. ANKRD1 was the most and commonly upregulated gene in the four EGFR-TKIs-resistant cell lines. Long-term exposure of lung cancer cells to EGFRTKIs may lead to accumulation of ANKRD1 protein. ANKRD1 inhibition or imatinib targeting ANKRD1 could rescue the acquired resistance to afatinib or osimertinib in EGFR-mutant cells. Recovery of the sensitivity to afatinib and osimertinib was also observed after imatinib treatment. Reference: Sci Rep. 2018; 8: 14896. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6173712/

In vivo activity:

To explore the influence of CYP1A enzymes on osimertinib disposition in vivo, this study carried out pharmacokinetic analysis in novel Cyp1a1/1a2 knockout and CYP1A1/1A2 humanized mouse lines. The basal expression of CYP1A1 in the h1A1/1A2 line is low, however it can be induced in a number of tissues including liver, lung, and small intestine by exposure of the mice to TCDD, an activator of the Ah receptor (Ahr). In h1A1/1A2 mice pretreated with TCDD, there was a 3.4-fold decrease in AUC0−t and a 3.3-fold decrease in Cmax of osimertinib (Fig. 5A and Supplementary Table S7). There was no change in exposure in the 1a1/1a2KO line. Correspondingly, TCDD-pretreatment greatly increased circulating levels of the OH-1 metabolite in humanized mice, but had no effect in knockouts (Fig. 5B). In this experiment, TCDD-mediated activation of Ahr occurred in several tissues—liver, small intestine, and lung—hence the effects on osimertinib and metabolite disposition were likely to be driven by a combination of hepatic, intestinal, and pulmonary CYP1A1/1A2. Reference: Clin Cancer Res. 2018 May 1;24(9):2138-2147. https://clincancerres.aacrjournals.org/content/24/9/2138.long

	Solvent	mg/mL	mM
Solubility
	DMSO	10.0	16.78

Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

Preparing Stock Solutions

The following data is based on the product molecular weight 595.72 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:

1. Takahashi A, Seike M, Chiba M, Takahashi S, Nakamichi S, Matsumoto M, Takeuchi S, Minegishi Y, Noro R, Kunugi S, Kubota K, Gemma A. Ankyrin Repeat Domain 1 Overexpression is Associated with Common Resistance to Afatinib and Osimertinib in EGFR-mutant Lung Cancer. Sci Rep. 2018 Oct 5;8(1):14896. doi: 10.1038/s41598-018-33190-8. PMID: 30291293; PMCID: PMC6173712. 2. Chagoya G, Kwatra SG, Nanni CW, Roberts CM, Phillips SM, Nullmeyergh S, Gilmore SP, Spasojevic I, Corcoran DL, Young CC, Ballman KV, Ramakrishna R, Cross DA, Markert JM, Lim M, Gilbert MR, Lesser GJ, Kwatra MM. Efficacy of osimertinib against EGFRvIII+ glioblastoma. Oncotarget. 2020 Jun 2;11(22):2074-2082. doi: 10.18632/oncotarget.27599. PMID: 32547705; PMCID: PMC7275784. 3. MacLeod AK, Lin D, Huang JT, McLaughlin LA, Henderson CJ, Wolf CR. Identification of Novel Pathways of Osimertinib Disposition and Potential Implications for the Outcome of Lung Cancer Therapy. Clin Cancer Res. 2018 May 1;24(9):2138-2147. doi: 10.1158/1078-0432.CCR-17-3555. Epub 2018 Feb 6. PMID: 29437786. 4. 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

In vitro protocol:

In vivo protocol:

1. MacLeod AK, Lin D, Huang JT, McLaughlin LA, Henderson CJ, Wolf CR. Identification of Novel Pathways of Osimertinib Disposition and Potential Implications for the Outcome of Lung Cancer Therapy. Clin Cancer Res. 2018 May 1;24(9):2138-2147. doi: 10.1158/1078-0432.CCR-17-3555. Epub 2018 Feb 6. PMID: 29437786. 2. 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

1: Zhang Z, Yang S, Wang Q. Impact of MET alterations on targeted therapy with EGFR-tyrosine kinase inhibitors for EGFR-mutant lung cancer. Biomark Res. 2019 Nov 21;7:27. doi: 10.1186/s40364-019-0179-6. eCollection 2019. Review. PubMed PMID: 31832192; PubMed Central PMCID: PMC6873421. 2: Shetty V, Babu S. Management of CNS metastases in patients with EGFR mutation-positive NSCLC. Indian J Cancer. 2019 Nov;56(Supplement):S31-S37. doi: 10.4103/ijc.IJC_455_19. Review. PubMed PMID: 31793440. 3: Doval DC, Desai CJ, Sahoo TP. Molecularly targeted therapies in non-small cell lung cancer: The evolving role of tyrosine kinase inhibitors. Indian J Cancer. 2019 Nov;56(Supplement):S23-S30. doi: 10.4103/ijc.IJC_449_19. Review. PubMed PMID: 31793439. 4: Rebuzzi SE, Alfieri R, La Monica S, Minari R, Petronini PG, Tiseo M. Combination of EGFR-TKIs and chemotherapy in advanced EGFR mutated NSCLC: Review of the literature and future perspectives. 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Available from http://www.ncbi.nlm.nih.gov/books/NBK548495/ PubMed PMID: 31643814. 8: Gelatti ACZ, Drilon A, Santini FC. Optimizing the sequencing of tyrosine kinase inhibitors (TKIs) in epidermal growth factor receptor (EGFR) mutation-positive non-small cell lung cancer (NSCLC). Lung Cancer. 2019 Nov;137:113-122. doi: 10.1016/j.lungcan.2019.09.017. Epub 2019 Sep 23. Review. PubMed PMID: 31568888. 9: Leonetti A, Sharma S, Minari R, Perego P, Giovannetti E, Tiseo M. Resistance mechanisms to osimertinib in EGFR-mutated non-small cell lung cancer. Br J Cancer. 2019 Oct;121(9):725-737. doi: 10.1038/s41416-019-0573-8. Epub 2019 Sep 30. Review. PubMed PMID: 31564718; PubMed Central PMCID: PMC6889286. 10: Masood A, Kancha RK, Subramanian J. Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors in non-small cell lung cancer harboring uncommon EGFR mutations: Focus on afatinib. Semin Oncol. 2019 Jun;46(3):271-283. doi: 10.1053/j.seminoncol.2019.08.004. Epub 2019 Sep 11. Review. PubMed PMID: 31558282. 11: Wang S, Li J. Second-generation EGFR and ErbB tyrosine kinase inhibitors as first-line treatments for non-small cell lung cancer. Onco Targets Ther. 2019 Aug 15;12:6535-6548. doi: 10.2147/OTT.S198945. eCollection 2019. Review. PubMed PMID: 31496745; PubMed Central PMCID: PMC6700283. 12: Xu ZY, Li JL. Comparative review of drug-drug interactions with epidermal growth factor receptor tyrosine kinase inhibitors for the treatment of non-small-cell lung cancer. Onco Targets Ther. 2019 Jul 9;12:5467-5484. doi: 10.2147/OTT.S194870. eCollection 2019. Review. PubMed PMID: 31371986; PubMed Central PMCID: PMC6636179. 13: Peters GJ. From 'Targeted Therapy' to Targeted Therapy. Anticancer Res. 2019 Jul;39(7):3341-3345. doi: 10.21873/anticanres.13476. Review. PubMed PMID: 31262854. 14: Wang Q, Yang S, Wang K, Sun SY. MET inhibitors for targeted therapy of EGFR TKI-resistant lung cancer. J Hematol Oncol. 2019 Jun 21;12(1):63. doi: 10.1186/s13045-019-0759-9. Review. PubMed PMID: 31227004; PubMed Central PMCID: PMC6588884. 15: Wang X, Zhong D. [Advanced Research on Non-small Cell Lung Cancer with De Novo T790M Mutation]. Zhongguo Fei Ai Za Zhi. 2019 May 20;22(5):324-328. doi: 10.3779/j.issn.1009-3419.2019.05.10. Review. Chinese. PubMed PMID: 31109443. 16: Singhi EK, Horn L, Sequist LV, Heymach J, Langer CJ. Advanced Non-Small Cell Lung Cancer: Sequencing Agents in the EGFR-Mutated/ALK-Rearranged Populations. Am Soc Clin Oncol Educ Book. 2019 Jan;39:e187-e197. doi: 10.1200/EDBK_237821. Epub 2019 May 17. Review. PubMed PMID: 31099642. 17: Rajappa S, Krishna MV, Narayanan P. Integrating Osimertinib in Clinical Practice for Non-Small Cell Lung Cancer Treatment. Adv Ther. 2019 Jun;36(6):1279-1290. doi: 10.1007/s12325-019-00917-6. Epub 2019 Apr 2. Review. PubMed PMID: 30941723. 18: Russo A, Franchina T, Ricciardi G, Battaglia A, Picciotto M, Adamo V. 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