MedKoo Biosciences, Inc.
Tel:   +1-919-636-5577    Fax:   +1-919-980-4831    Email:   sales@medkoo.com
Search
Login Register
Search
MedKoo Cat#: 206042 | Name: Osimertinib free base
Featured New

Description:

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

Osimertinib, also known as AZD-9291 and Mereletinib, 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 in Nov. 2015 by FDA.

Chemical Structure

Osimertinib free base
Osimertinib free base
CAS#1421373-65-0 (free base)

Theoretical Analysis

MedKoo Cat#: 206042

Name: Osimertinib free base

CAS#: 1421373-65-0 (free base)

Chemical Formula: C28H33N7O2

Exact Mass: 499.2696

Molecular Weight: 499.61

Elemental Analysis: C, 67.31; H, 6.66; N, 19.62; O, 6.40

Price and Availability

Size Price Availability Quantity
500mg USD 90.00 Ready to ship
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
Show More
Bulk Inquiry
Buy Now
Add to Cart
Related CAS #
1421373-65-0 (free base) 1421373-66-1 (mesylate)
Synonym
AZD9291; AZD 9291; AZD-9291; AZD-9291 freebase; Mereletinib; Osimertinib free base; trade 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
InChi Key
DUYJMQONPNNFPI-UHFFFAOYSA-N
InChi Code
InChI=1S/C28H33N7O2/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/h7-13,16-18H,1,14-15H2,2-6H3,(H,30,36)(H,29,31,32)
SMILES Code
C=CC(NC1=CC(NC2=NC=CC(C3=CN(C)C4=C3C=CC=C4)=N2)=C(OC)C=C1N(CCN(C)C)C)=O
Appearance
Brown to 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)
Biological target:
Osimertinib (AZD-9291) is an irreversible and mutant selective EGFR inhibitor with IC50s of 12 and 1 nM against EGFRL858R and EGFRL858R/T790M, respectively.
In vitro activity:
EGFR T790M mutant NCI-H1975 cells were treated with different concentrations of osimertinib. After treatment for 24 h, osimertinib clearly inhibited EGFR phosphorylation and significantly reduced the protein levels of PD-L1 (Figure 1A). NCI-H1975 cells were then incubated with 125 nmol/L osimertinib for different durations (3, 6, 12 and 24 h). As shown in Figure 1B, osimertinib down-regulated PD-L1 expression at 6 h. Furthermore, immunofluorescence was used to localize PD-L1 in NCI-H1975 cells. Compared with the osimertinib-untreated group, cell membranes exhibited weak PD-L1 signals at 6 and 24 h (Figure 1C). Consistently, the reduction of PD-L1 on the membranes was confirmed further by flow cytometry after treatment with osimertinib for 6 and 24 h (Figure 1D). To exclude the massive suppression of PD-L1 mRNA and protein expression caused by cell death, this study performed MTT assays to examine the cell viability after treatment with osimertinib. This study found that osimertinib could not trigger cell death in NCI-H1975 cells at 6 h (Figure 1E), which was further verified in HCC827 cells (data not shown). In addition, the apoptosis inhibitor Z-VAD-FMK and the necroptosis inhibitor NSA failed to reverse the osimertinib-triggered decrease of PD-L1 in NCI-H1975 cells (Figure 1F). Collectively, these findings demonstrate that osimertinib reduces PD-L1 expression in NCI-H1975 cells independent of cell death. Reference: Acta Pharmacol Sin. 2017 Nov; 38(11): 1512–1520. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5672073/
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 15.0 30.00
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 499.61 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.

Recalculate based on batch purity %
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. 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. 2. Jiang XM, Xu YL, Huang MY, Zhang LL, Su MX, Chen X, Lu JJ. Osimertinib (AZD9291) decreases programmed death ligand-1 in EGFR-mutated non-small cell lung cancer cells. Acta Pharmacol Sin. 2017 Nov;38(11):1512-1520. doi: 10.1038/aps.2017.123. Epub 2017 Sep 7. PMID: 28880013; PMCID: PMC5672073. 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. 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. 2. Jiang XM, Xu YL, Huang MY, Zhang LL, Su MX, Chen X, Lu JJ. Osimertinib (AZD9291) decreases programmed death ligand-1 in EGFR-mutated non-small cell lung cancer cells. Acta Pharmacol Sin. 2017 Nov;38(11):1512-1520. doi: 10.1038/aps.2017.123. Epub 2017 Sep 7. PMID: 28880013; PMCID: PMC5672073.
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. Crit Rev Oncol Hematol. 2019 Oct 31:102820. doi: 10.1016/j.critrevonc.2019.102820. [Epub ahead of print] Review. PubMed PMID: 31785991. 5: Zhu VW, Klempner SJ, Ou SI. Receptor Tyrosine Kinase Fusions as an Actionable Resistance Mechanism to EGFR TKIs in EGFR-Mutant Non-Small-Cell Lung Cancer. Trends Cancer. 2019 Nov;5(11):677-692. doi: 10.1016/j.trecan.2019.09.008. Epub 2019 Oct 29. Review. PubMed PMID: 31735287. 6: Solassol I, Pinguet F, Quantin X. FDA- and EMA-Approved Tyrosine Kinase Inhibitors in Advanced EGFR-Mutated Non-Small Cell Lung Cancer: Safety, Tolerability, Plasma Concentration Monitoring, and Management. Biomolecules. 2019 Oct 30;9(11). pii: E668. doi: 10.3390/biom9110668. Review. PubMed PMID: 31671561. 7: LiverTox: Clinical and Research Information on Drug-Induced Liver Injury [Internet]. Bethesda (MD): National Institute of Diabetes and Digestive and Kidney Diseases; 2012-. 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. Heterogeneous Responses to Epidermal Growth Factor Receptor (EGFR) Tyrosine Kinase Inhibitors (TKIs) in Patients with Uncommon EGFR Mutations: New Insights and Future Perspectives in this Complex Clinical Scenario. Int J Mol Sci. 2019 Mar 21;20(6). pii: E1431. doi: 10.3390/ijms20061431. Review. PubMed PMID: 30901844; PubMed Central PMCID: PMC6470640. 19: Le T, Gerber DE. Newer-Generation EGFR Inhibitors in Lung Cancer: How Are They Best Used? Cancers (Basel). 2019 Mar 15;11(3). pii: E366. doi: 10.3390/cancers11030366. Review. PubMed PMID: 30875928; PubMed Central PMCID: PMC6468595. 20: Holleman MS, van Tinteren H, Groen HJ, Al MJ, Uyl-de Groot CA. First-line tyrosine kinase inhibitors in EGFR mutation-positive non-small-cell lung cancer: a network meta-analysis. Onco Targets Ther. 2019 Feb 20;12:1413-1421. doi: 10.2147/OTT.S189438. eCollection 2019. Review. PubMed PMID: 30863108; PubMed Central PMCID: PMC6388947.