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Osimertinib mesylate

Catalog No. T3634   CAS 1421373-66-1
Synonyms: Mereletinib mesylate, AZD-9291 mesylate

Osimertinib mesylate (Mereletinib mesylate) is an irreversible and mutant selective EGFR inhibitor (IC50s: 12/1 nM for EGFR(L858R) and EGFR(L858R/T790M)).

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Osimertinib mesylate Chemical Structure
Osimertinib mesylate, CAS 1421373-66-1
Pack Size Availability Price/USD Quantity
5 mg In stock $ 45.00
10 mg In stock $ 55.00
50 mg In stock $ 80.00
100 mg In stock $ 97.00
200 mg In stock $ 115.00
500 mg In stock $ 133.00
1 g In stock $ 155.00
1 mL * 10 mM (in DMSO) In stock $ 63.00
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Purity: 100%
Purity: 99.53%
Purity: 99.46%
Purity: 99.38%
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Biological Description
Chemical Properties
Storage & Solubility Information
Description Osimertinib mesylate (Mereletinib mesylate) is an irreversible and mutant selective EGFR inhibitor (IC50s: 12/1 nM for EGFR(L858R) and EGFR(L858R/T790M)).
Targets&IC50 EGFR L858R:12 nM (cell free), EGFR L858R/T790M:1 nM (cell free)
In vitro In EGFR recombinant enzyme assays, osimertinib (AZD9291) showed an apparent IC50 of 12 nM against L858R and 1 nM against L858R/T790M. The drug exhibited nearly 200 times greater potency against L858R/T790M than wild-type EGFR. AZD9291 showed similar potency to early generation TKIs in inhibiting EGFR phosphorylation in EGFR cells harboring sensitizing EGFR mutants including PC-9 (ex19del), H3255 (L858R) and H1650 (ex19del), with mean IC50 values ranging from 13 to 54 nM for AZD9291. AZD9291 also potently inhibited phosphorylation of EGFR in T790M mutant cell lines (H1975 (L858R/T790M), PC-9VanR (ex19del/T790M), with mean IC50 potency less than 15 nM [1]. In the presence of osimertinib, the intracellular accumulations of DOX and Rho 123 significantly increased in KBv200 and S1-MI-80 cells while not in the sensitive KB and S1 cells. Osimertinib increased the intracellular accumulation of Hoechst 33342 in resistant H460/MX20 and HEK293/ABCG2 cells rather than in sensitive H460 and HEK293/Vector cells. Furthermore, the increased effect produced by osimertinib at 0.2 μmol/L or 0.4 μmol/L was comparable with that of FTC at 2.5 μmol/L or VRP at 10 μmol/L [2].
In vivo Once daily dosing of AZD9291 induced significant dose-dependent regression in both PC-9 (ex19del) and H1975 (L858R/T790M) tumor xenograft models, with tumor shrinkage observed at doses as low as 2.5mg/kg/day in both models after 14 days. Similar tumor shrinkage was seen after administration of 5 mg/kg/day AZD9291 in H3255 (L858R) and PC-9VanR (ex19 del/ T790M) xenografts after 14 days [1]. The combination of osimertinib and paclitaxel produced a greater inhibitory effect on xenograft growth compared with animals treated with only saline, paclitaxel, or osimertinib, and the inhibition rate was 52.7% [2]. AZD9291 demonstrated improved rat PK, reduced hERG affinity, and improved IGF1R margins. AZD9291 also offered an additional degree of broader chemical and profile diversity. Upon dosing AZD9291 in our three efficacy models, comparable efficacy was observed at relatively low doses (10 mg/kg/day). Excellent efficacy was also observed when 8 was dosed at 5 mg/kg/day [3].
Kinase Assay Kinase assays were performed as per the EMD Millipore profiling service protocol using peptide or protein substrates in a filter-binding radioactive ATP transferase assay for protein [1].
Cell Research PC-9 cells were seeded into T75 flasks (5 × 10^5 cells/flask) in RPMI growth media and incubated at 37°C, 5% CO2. The following day the media was replaced with media supplemented with a concentration of EGFR inhibitor equal to the EC50 concentration predetermined in PC-9 cells. Media changes were carried out every 2-3 days and resistant clones allowed to grow to 80% confluency prior to the cells being trypsinised and reseeded at the original seeding density in media containing twice the concentration of EGFR inhibitor. Dose escalations were continued until a final concentration of 1.5μM gefitinib, 1.5μM afatinib, 1.5μM WZ4002 or 160nM AZD9291 were achieved [1].
Animal Research The generation of EGFRL858R and EGFRL858R+T790M mice (male and female) was previously described Doxycycline was administered by feeding mice (aprox 3 week old) with doxycycline-impregnated food pellets (625 ppm) and treated for about 3 months during which time tumors developed. Afatinib and AZD9291 were suspended in 1% Polysorbate 80 and administered via oral gavage once daily at the doses of 7.5 mg/kg and 5 mg/kg, respectively. Mice were imaged weekly at the Vanderbilt University Institute of Imaging Science. For immunoblot analysis, mice were treated for eight hours with drug as described before dissection and flash freezing of the lungs. Lungs were pulverized in liquid nitrogen before lysis as described above [1].
Synonyms Mereletinib mesylate, AZD-9291 mesylate
Molecular Weight 595.71
Formula C29H37N7O5S
CAS No. 1421373-66-1

Storage

Powder: -20°C for 3 years | In solvent: -80°C for 1 year

Solubility Information

DMSO: 5.96 mg/mL (10 mM), Sonification is recommended

H2O: 33 mg/mL (55 mM), Sonification is recommended

TargetMolReferences and Literature

1. Cross DA, et al. AZD9291, an irreversible EGFR TKI, overcomes T790M-mediated resistance to EGFR inhibitors in lung cancer. Cancer Discov. 2014 Sep;4(9):1046-61. 2. Chen Z, et al. Osimertinib (AZD9291) Enhanced the Efficacy of Chemotherapeutic Agents in ABCB1- and ABCG2-Overexpressing Cells In Vitro, In Vivo, and Ex Vivo. Mol Cancer Ther. 2016 Aug;15(8):1845-58. 3. Finlay MR, et al. Discovery of a potent and selective EGFR inhibitor (AZD9291) of both sensitizing and T790M resistancemutations that spares the wild type form of the receptor. J Med Chem. 2014 Oct 23;57(20):8249-67.

TargetMolCitations

1. Liu N N, Zhou J, Jiang T, et al. A dual action small molecule enhances azoles and overcomes resistance through co-targeting Pdr5 and Vma1: Osimertinib targets Pdr5 and Vma1. Translational Research. 2022

Related compound libraries

This product is contained In the following compound libraries:
Anti-Cancer Clinical Compound Library Anti-Cancer Approved Drug Library Tyrosine Kinase Inhibitor Library Highly Selective Inhibitor Library Anti-Cancer Drug Library Anti-Cancer Active Compound Library Bioactive Compound Library Anti-Prostate Cancer Compound Library Drug Repurposing Compound Library FDA-Approved Drug Library

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Keywords

Osimertinib mesylate 1421373-66-1 Angiogenesis JAK/STAT signaling Tyrosine Kinase/Adaptors EGFR Osimertinib Osimertinib Mesylate PC-9 tumor xenograft model inhibit AZD9291 AZD-9291 cancer Mereletinib mesylate Inhibitor Epidermal growth factor receptor Mereletinib HER1 H1975 AZD 9291 Mereletinib Mesylate ErbB-1 AZD-9291 Mesylate Ba/F3 cells AZD9291 Mesylate AZD-9291 mesylate AZD 9291 Mesylate inhibitor

 

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