OSIMERTINIB DIMESYLATE

Alias: AZD-9291 dimesylate; AZD9291; AZD 9291; Mereletinib dimesylate; Trade name: Tagrisso

Cat No.:V3976 Purity: ≥98%

COA Product Data Instructions for use SDS

OSIMERTINIB DIMESYLATE Chemical Structure CAS No.: 2070014-82-1
Product category: EGFR

This product is for research use only, not for human use. We do not sell to patients.

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Top Publications Citing lnvivochem Products

Nature 2021, 597(7874):119-125.

Cell 2020,183:1202-1218.e25.

Science Adv 2022: 8, eabm9427.

Nature 597, 119–125 (2021)

Cell Stem Cell 2020,26(6):845-861.e12.

Science Trans Med 2023,15(701):eadd7872.

STTT 2023,8(1):91.

Cell Reports 2023,42(4):112313

Science Trans Med 2023, 15: eadd7872.

Cancer Cell 2021,39(4):529-547.e7.

Cancer Discov 2022,12(4):1106-1127.

Immunity 2023,56(3):620-634.e11.

J Am Chem Soc 2022,144:21831-21836.

Cell 2020,183:1202-1218.e25.

Science Adv 2022:8,eabm9427.

Nature 2021,597(7874):119-125.

Cell 2020,183:1202-1218.e25.

PNAS Nexus 2022,1(3):pgac063.

ACS Nano 2023,17(10):9110-9125.

Biomaterial 2023 Sep16:302:122333.

Purity & Quality Control Documentation

Current batch：

Purity: ≥98%

COA

MSDS

Instructions

Product Description
Bioactivity & Protocols
Physicochemical Properties
Solubility Data
Calculators
Biological Data

Product Description

Osimertinib dimesylate (mereletinib; AZD 9291; AZD9291; AZD-9291; trade name Tagrisso), the dimesylate salt of osimertinib, is an oral bioavailable and covalent/irreversible EGFR inhibitor approved as a cancer treatment in 2017 by both the Food and Drug Administration and the European Commission. It inhibits EGFR mutants (WT EGFR, L858R/T790M EGFR, and Exon 19 deletion EGFR) with IC50 values in LoVo cells of 12.92, 11.44, and 493.8 nM, respectively.

Biological Activity I Assay Protocols (From Reference)

Targets

EGFR^L858R (IC50 = 12 nM); EGFR^L858R/T790M (IC50 = 1 nM)

ln Vitro

Osimertinib (AZD-9291) has mean IC50 values ranging from 13 to 54 nM. It is comparable in potency to early generation tyrosine kinase inhibitors (TKIs) in inhibiting EGFR phosphorylation in EGFR cells harboring sensitizing EGFR mutants such as PC-9 (ex19del), H3255 (L858R), and H1650 (ex19del). With mean IC50 potency less than 15 nM, osimertinib (AZD-9291) also potently inhibits EGFR phosphorylation in T790M mutant cell lines (H1975 (L858R/T790M), PC-9VanR (ex19del/T790M)[1].

ln Vivo

Osimertinib (AZD-9291) (5 mg/kg/day) is administered to the tumor-bearing mice for a duration of one to two weeks. After receiving Osimertinib (AZD-9291) therapy, 5 out of 5 C/L858R mice showed an almost 80% reduction in tumor volume by magnetic resonance imaging (MRI) within days of treatment, whereas 5 out of 5 mice given a vehicle treatment showed tumor growth[1]. Osimertinib (AZD-9291) is chosen for additional research because it exhibits better rat PK, decreased hERG affinity, and improved IGF1R margins in comparison to the previously reported compounds. Comparing osimertinib (AZD-9291) to the previously reported lead compounds, it also provides a further level of wider chemical and profile diversity. In three efficacy models, Osimertinib (AZD-9291) doses comparatively well; comparable efficacy is seen at doses of 10 mg/kg per day. When Osimertinib (AZD-9291) is dosed at 5 mg/kg per day, even greater efficacy is seen[2].

Enzyme Assay

Osimertinib, formerly known as mereletinib and AZD-9291, is a third generation EGFR inhibitor that is available orally and is irreversible. It selectively targets specific mutants of EGFR, with IC50 values of 493.8 nM for wild-type EGFR in LoVo cells, L858R/T790M EGFR, and Exon 19 deletion EGFR, respectively. It reduces the side effects associated with currently available medications by inhibiting both activating and resistant EGFR mutations while protecting the normal form of EGFR found in normal skin and gut cells.

Cell Assay

PC-9 cells are cultured at 37°C with 5% CO₂ after being seeded into T75 flasks (5×10⁵ cells/flask) with RPMI growth media. The medium is changed the next day to one supplemented with an EGFR inhibitor at a concentration equivalent to the predetermined EC50 in PC-9 cells. Every two to three days, the medium is changed, and resistant clones are allowed to reach 80% confluency before the cells are trypsinized and reseeded in the same amount of media that contains twice as much EGFR inhibitor. Until a final concentration of 1.5 μM ZD1839, 1.5 μM BIBW 2992, 1.5 μM WZ4002, or 160 nM Osimertinib (AZD-9291) is reached, dose escalations are carried out[1].

Animal Protocol

Mice: The mice used are male and female EGFR^L858R and EGFR^L858R+T790M mice. Oral gavage is used to administer osimertinib (AZD-9291) at a dose of 7.5 mg/kg and 5 mg/kg, respectively. The drug is suspended in 1% Polysorbate 80. Every week, the Vanderbilt University Institute of Imaging Science images mice. Prior to lung dissection and flash freezing, mice are given a drug treatment for eight hours in preparation for immunoblot analysis. Liquid nitrogen is used to grind the lungs before lysis.
Rats: The 10-week-old male RccHan:WIST rats are given a single oral dose of 200 mg/kg of osimertinib (AZD-9291). Accuchek Active meters are used to measure blood glucose levels.

References

[1]. AZD9291, an irreversible EGFR TKI, overcomes T790M-mediated resistance to EGFR inhibitors in lung cancer. Cancer Discov. 2014 Sep;4(9):1046-61.

[2]. 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.

These protocols are for reference only. InvivoChem does not independently validate these methods.

Physicochemical Properties

Molecular Formula	C₃₀H₄₁N₇O₈S₂
Molecular Weight	691.82
Exact Mass	691.24580364
CAS #	2070014-82-1
Related CAS #	Osimertinib;1421373-65-0;Osimertinib mesylate;1421373-66-1
Appearance	Solid
SMILES	CN1C=C(C2=CC=CC=C21)C3=NC(=NC=C3)NC4=C(C=C(C(=C4)NC(=O)C=C)N(C)CCN(C)C)OC.CS(=O)(=O)O.CS(=O)(=O)O
InChi Key	RPUCCTLBBCSFEX-UHFFFAOYSA-N
InChi Code	InChI=1S/C28H33N7O2.2CH4O3S/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;2*1-5(2,3)4/h7-13,16-18H,1,14-15H2,2-6H3,(H,30,36)
Chemical Name	N-[2-[2-(dimethylamino)ethyl-methylamino]-4-methoxy-5-[[4-(1-methylindol-3-yl)pyrimidin-2-yl]amino]phenyl]prop-2-enamide;methanesulfonic acid
Synonyms	AZD-9291 dimesylate; AZD9291; AZD 9291; Mereletinib dimesylate; Trade name: Tagrisso
Storage	Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month
Shipping Condition	Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Solubility Data

Solubility (In Vitro)

DMSO: <1 mg/mL

Water: <1 mg/mL

Ethanol: <1 mg/mL

Solubility (In Vivo)

1% DMSO+30% PEG 300+dd H2O: 30mg/mL

(Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	1.4455 mL	7.2273 mL	14.4546 mL
	5 mM	0.2891 mL	1.4455 mL	2.8909 mL
	10 mM	0.1445 mL	0.7227 mL	1.4455 mL

*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.

Calculator

Mass

Concentration

Volume

Molecular Weight*

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Molarity Calculator allows you to calculate the mass, volume, and/or concentration required for a solution, as detailed below:

Calculate the Mass of a compound required to prepare a solution of known volume and concentration
Calculate the Volume of solution required to dissolve a compound of known mass to a desired concentration
Calculate the Concentration of a solution resulting from a known mass of compound in a specific volume

See Example

An example of molarity calculation using the molarity calculator is shown below:
What is the mass of compound required to make a 10 mM stock solution in 5 ml of DMSO given that the molecular weight of the compound is 350.26 g/mol?

Enter 350.26 in the Molecular Weight (MW) box
Enter 10 in the Concentration box and choose the correct unit (mM)
Enter 5 in the Volume box and choose the correct unit (mL)
Click the “Calculate” button
The answer of 17.513 mg appears in the Mass box. In a similar way, you may calculate the volume and concentration.

Concentration (Start)

Volume (Start)

Concentration (End)

Volume (End)

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Dilution Calculator allows you to calculate how to dilute a stock solution of known concentrations. For example, you may Enter C1, C2 & V2 to calculate V1, as detailed below:

What volume of a given 10 mM stock solution is required to make 25 ml of a 25 μM solution?
Using the equation C1V1 = C2V2, where C1=10 mM, C2=25 μM, V2=25 ml and V1 is the unknown:

Enter 10 into the Concentration (Start) box and choose the correct unit (mM)
Enter 25 into the Concentration (End) box and select the correct unit (mM)
Enter 25 into the Volume (End) box and choose the correct unit (mL)
Click the “Calculate” button
The answer of 62.5 μL (0.1 ml) appears in the Volume (Start) box

Molecular formula

Total molecular weight

g/mol

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Molecular Weight Calculator allows you to calculate the molar mass and elemental composition of a compound, as detailed below:

Note: Chemical formula is case sensitive: C12H18N3O4 c12h18n3o4
Instructions to calculate molar mass (molecular weight) of a chemical compound:

To calculate molar mass of a chemical compound, please enter the chemical/molecular formula and click the “Calculate’ button.

Definitions of molecular mass, molecular weight, molar mass and molar weight:

Molecular mass (or molecular weight) is the mass of one molecule of a substance and is expressed in the unified atomic mass units (u). (1 u is equal to 1/12 the mass of one atom of carbon-12)
Molar mass (molar weight) is the mass of one mole of a substance and is expressed in g/mol.

Volume (to add to vial)

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Desired Reconstitution Concentration

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Reconstitution Calculator allows you to calculate the volume of solvent required to reconstitute your vial.

Enter the mass of the reagent and the desired reconstitution concentration as well as the correct units
Click the “Calculate” button
The answer appears in the Volume (to add to vial) box

In vivo Formulation Calculator (Clear solution)

Step 1: Enter information below (Recommended: An additional animal to make allowance for loss during the experiment)

Dosage mg/kg

Average weight of animals g

Dosing volume per animal μL

Number of animals

Step 2: Enter in vivo formulation (This is only a calculator, not the exact formulation for a specific product. Please contact us first if there is no in vivo formulation in the solubility section.)

% DMSO

% Tween 80

% ddH₂O

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Calculation results

Working concentration： mg/mL；

Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.

Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH₂O，mix and clarify.

Note： (1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.

Biological Data

AZD9291 binding mode and structure.Cancer Discov.2014 Sep;4(9):1046-61.
Effect of AZD9291 on EGFR phosphorylationin vitro.Cancer Discov.2014 Sep;4(9):1046-61.
In vivoanti-tumor efficacy of AZD9291 in subcutaneous xenograft models of EGFR-TKI sensitising and T790M resistant lung cancer.Cancer Discov.2014 Sep;4(9):1046-61.
AZD9291 induces significant and sustained tumor regression in transgenic models of EGFR-TKI sensitising (C/L858R) and T790M resistant (C/L+T) lung cancer.Cancer Discov.2014 Sep;4(9):1046-61.
AZD9291 inhibits EGFR phosphorylation and downstream signallng in murine models of EGFR T790M resistant lung cancer.Cancer Discov.2014 Sep;4(9):1046-61.
Proof of concept clinical studies validating AZD9291 as a mutant-selective EGFR kinase T790M inhibitor.Cancer Discov.2014 Sep;4(9):1046-61.