WARNING: This product is for research use only, not for human or veterinary use.
MedKoo CAT#: 206426
CAS#: 1421373-66-1 (mesylate)
Description: 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.
MedKoo Cat#: 206426
Name: Osimertinib mesylate
CAS#: 1421373-66-1 (mesylate)
Chemical Formula: C29H37N7O5S
Molecular Weight: 595.72
Elemental Analysis: C, 58.47; H, 6.26; N, 16.46; O, 13.43; S, 5.38
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
|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||Max Conc. mg/mL||Max Conc. mM|
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:||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.|
|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|
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CAS#1421373-65-0 (Osimertinib free base);
CAS#1421373-66-1 (Osimertinib mesylate salt)