Osimertinib mesylate

SKU: orb1303975

Description

Osimertinib mesylate is an orally active, irreversible third-generation EGFR inhibitor designed to target the T790M resistance mutation in non-small cell lung cancer. It is widely used in both in vitro biochemical assays and in vivo xenograft models to study resistance mechanisms and evaluate therapeutic efficacy against EGFR-mutant tumors.

Research Area

Cardiovascular Research, Signal Transduction

Images & Validation

−

Key Properties

−

CAS Number	1421373-66-1
MW	595.71
Purity	99.88%
Formula	C₂₉H₃₇N₇O₅S
SMILES	CS(O)(=O)=O.COc1cc(N(C)CCN(C)C)c(NC(=O)C=C)cc1Nc1nccc(n1)-c1cn(C)c2ccccc12
Target	EGFR
Solubility	10% DMSO+40% PEG300+5% Tween 80+45% Saline:1 mg/mL (1.68 mM);DMSO:14 mg/mL (23.5 mM);H2O:20 mg/mL (33.57 mM)

Bioactivity

−

Target IC50	EGFR (L858R/T790M):1 nM (cell free)\|EGFR (L858R):12 nM (cell free)
In Vivo	METHODS: To detect anti-tumor activity in vivo, Osimertinib mesylate (5-10 mg/kg) was orally administered once daily for seven days to SCID mice bearing human lung cancer tumors H1975, PC9 and A431. RESULTS: Osimertinib treatment significantly inhibited the growth of H1975, PC9 and A431 tumors, indicating antitumor activity in vivo. METHODS: To detect the anti-tumor activity in vivo, Osimertinib mesylate (6 mg/kg) was administered orally to SHO-SCID mice constructed with PC-9/ffluc cells as a model of leptomeningeal carcinomatosis (LMC) once daily for fifty days. RESULTS: Osimertinib treatment significantly delayed the progression of LMC. Osimertinib, a third-generation EGFR-TKI, may be an effective treatment for first- or second-generation EGFR-TKI-resistant LMC caused by EGFR-mutant tumors. Read more...
In Vitro	METHODS: Human non-small cell lung cancer cells PC-9 (exon 19del), H3255 (L858R), PC-9ER (exon 19del+T790M) and H1975 (L858R+T790M) were treated with Osimertinib mesylate (0.0001-10 µmol/L) for 72 h, and the growth inhibition of the cells was detected by using MTS method. growth inhibition was detected using the MTS. RESULTS: Osimertinib dose-dependently induced the growth of PC-9, H3255, PC-9ER, and H1975 cells with IC50s of 41, 26, 41, and 31 nM, respectively. METHODS: EGFR-mutated human non-small cell lung cancer cells PC-9, H1975, H1650 and H3255 were treated with Osimertinib mesylate (0.1-1000 nM) for 6 h, and the expression levels of the target proteins were detected by Western Blot. RESULTS: Osimertinib inhibited pEGFR (Y1068), pERK (P-p44/42), and pAKT (S473) in EGFR mutant tumor cells. METHODS: Human non-small cell lung cancer cells NCI-H1975 were treated with Osimertinib mesylate (10-100 nM) for 24 h, then irradiated with 2-20 Gy, and the cell cycle was analyzed by Flow Cytometry. RESULTS: The proportion of G2/M and S-phase cells was dose-dependently reduced in the combination treatment group, and the G2/M-phase cell cycle was arrested after reduced irradiation with Osimertinib. Read more...
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 . Read more...
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 . Read more...

Storage & Handling

−

Storage	store at low temperature,store under nitrogen \| Powder: -20°C for 3 years \| In solvent: -80°C for 1 year \| Shipping with blue ice/Shipping at ambient temperature.
Expiration Date	12 months from date of receipt.
Disclaimer	For research use only

Alternative Names

−

tumor xenograft model, H1975, Epidermal growth factor receptor, EGFR, EGFR (L858R), EGFR (L858R/T790M), ErbB-1, HER1, Inhibitor, Mereletinib mesylate, Mereletinib Mesylate, Mereletinib, inhibit, Osimertinib Mesylate, Osimertinib mesylate, Osimertinib, PC-9, AZD-9291 mesylate, AZD-9291, AZD9291, AZD9291 Mesylate, AZD-9291 Mesylate, AZD 9291, AZD 9291 Mesylate, cancer, Ba/F3 cells

Quality Guarantee

Explore bioreagents carefree to elevate your research. All our products are rigorously tested for performance. If a product does not perform as described on its datasheet, our scientific support team will provide expert troubleshooting, a prompt replacement, or a refund. For full details, please see our Terms & Conditions and Buying Guide. Contact us at support@biorbyt.com.

Compound Identifiers

PubChem CID

78357807 ↗

Key Properties

−

No computed properties available.

Documents Download

Datasheet

Product Information

Download

Request a Document

Protocol Information

Find More Protocols