Osimertinib-d6 - ≥99% , CAS No.1638281-44-3

CAS: 1638281-44-3 Cat. No.: O646850 Molecular Weight: 505.64

GRADE & PURITY ≥99%

Storage

Store at 2-8°C,Protected from light,Argon charged

Shipped In

Wet ice

Overview

Osimertinib-d 6 is a deuterium labeled osimertinib. Osimertinib is a covalent, orally active, irreversible, and mutant-selective EGFR inhibitor with an apparent IC50 of 12 nM against L858R and 1 nM against L858R/T790M. Osimertinib overcomes T790M-mediated resistance to EGFR inhibitors in lung cancer.

In Vitro

Osimertinib (AZD9291) (0-10 μM; 72 hours) dramatically inhibits cell proliferation with IC 50 s of 41, 26, 41, and 31 nM, respectively. Osimertinib (0-10 μM; 72 hours) inhibits cell proliferation (Ba/F3 cells harboring a T790M mutation, exon 19del+T790M, or L858R+T790M) with IC 50 s of 6, 7, and 74 nM, respectively. Osimertinib (0-10 μM; 72 hours) inhibits Ba/F3 cells harboring EGFR exon 20 insertion mutations (IC 50 ranging from 16-701 nM for A763_Y764insFQEA (FQEA), Y764_V765insHH (HH), A767_V769dupASV (ASV), and D770_N771insNPG (NPG) cells). Osimertinib shows high levels of phenotype potency in both sensitizing-mutant (mean IC 50 of 8 nM in PC-9) and T790M (mean IC 50 of 11 and 40 nM in H1975 and PC-9VanR respectively) EGFR cell lines. Osimertinib has much less activity towards wild-type EGFR (mean IC 50 of 650 and 461 nM in Calu3 and H2073 respectively). Osimertinib (0.1 μM; 48 hours) induces apoptosis in Ba/F3 cells (apoptosis rate of 40.9% and 90% in EGFR exon 19del+T790M, EGFR L858R+T790M respectively). MCE has not independently confirmed the accuracy of these methods. They are for reference only. Cell Proliferation AssayCell Line: PC-9, H3255, PC-9ER, and H1975 cells Concentration: 0.0001, 0.001, 0.01, 0.1, 1, 10 μM Incubation Time: 72 hours Result: Dramatically inhibited cell proliferation (IC 50 =41,26, 41, 31 nM, respectively) Cell Proliferation AssayCell Line: Ba/F3 cells (harboring a T790M mutation, exon 19del+T790M, or L858R+T790M) Concentration: 0.0001, 0.001, 0.01, 0.1, 1, 10 μM Incubation Time: 72 hours Result: Inhibited cell proliferation (IC 50 = 6, 7, 74 nM, respectively) Apoptosis AnalysisCell Line: Ba/F3 cells (harboring EGFR exon 20 insertion mutations) Concentration: 0.0001, 0.001, 0.01, 0.1, 1, 10 μM Incubation Time: 72 hours Result: Inhibited cell proliferation (IC 50 = 16, 701, 230, 38 nM, respectively) Apoptosis AnalysisCell Line: Ba/F3 cells(harboring EGFR exon 19del+T790M or EGFR L858R+T790M) Concentration: 0.1 μM Incubation Time: 48 hours Result: Inducted apoptosis with the rate of 40.9% and 90% in EGFR T790M positive mutations cells respectively.

In Vivo

Osimertinib (0.1-25 mg/kg; p.o.; daily for 14 day) induces significant dose-dependent regression in both PC-9 (ex19del) and H1975 (L858R/T790M) tumor xenograft models . MCE has not independently confirmed the accuracy of these methods. They are for reference only. Animal Model: PC-9 (ex19del) and H1975 (L858R/T790M) tumor xenograft models Dosage: 0.1-10 mg/kg (PC-9 xenograft models); 0.5- 25 mg/kg (H1975 xenograft models) Administration: p.o.; daily for 14 day Result: Induced significant dose-dependent regression in both PC-9 (ex19del) and H1975 (L858R/T790M) tumor xenograft models.

Form:Solid

Specifications

Specifications & Purity

≥99%

Biochemical and Physiological Mechanisms

Osimertinib-d 6 is a deuterium labeled osimertinib. Osimertinib is a covalent, orally active, irreversible, and mutant-selective EGFR inhibitor with an apparent IC50 of 12 nM against L858R and 1 nM against L858R/T790M. Osimertinib overcomes T790M-mediated

Storage

Store at 2-8°C, Protected from light, Argon charged

Shipped In

Wet ice

This product requires cold chain shipping. Ground and other economy services are not available.

Action Type

INHIBITOR

Purity

≥99%

Names and Identifiers

• Canonical 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
• IUPAC Name: N-[2-[2-[bis(trideuteriomethyl)amino]ethyl-methylamino]-4-methoxy-5-[[4-(1-methylindol-3-yl)pyrimidin-2-yl]amino]phenyl]prop-2-enamide
• InChIKey: DUYJMQONPNNFPI-XERRXZQWSA-N
• 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)/i2D3,3D3
• Isomeric SMILES: [2H]C([2H])([2H])N(CCN(C)C1=CC(=C(C=C1NC(=O)C=C)NC2=NC=CC(=N2)C3=CN(C4=CC=CC=C43)C)OC)C([2H])([2H])[2H]
• Molecular Weight: 505.64
• Reaxy-Rn: 23334373
• Reaxys-RN_link_address: https://www.reaxys.com/reaxys/secured/hopinto.do?context=S&query=IDE.XRN=23334373&ln=

Taxonomic Classification

Taxonomy Tree

• Kingdom Organic compounds
  • Superclass Benzenoids
    • Class Benzene and substituted derivatives
      • Subclass Anilides

• Kingdom: Organic compounds
• Superclass: Benzenoids
• Class: Benzene and substituted derivatives
• Subclass: Anilides
• Intermediate Tree Nodes: Not available
• Direct Parent: 2'-Aminoanilides
• Alternative Parents: N-alkylindoles Aminophenyl ethers Indoles Methoxyanilines Anisoles Dialkylarylamines Phenoxy compounds Methoxybenzenes N-arylamides Alkyl aryl ethers Aminopyrimidines and derivatives N-methylpyrroles Heteroaromatic compounds Acrylic acids and derivatives Secondary carboxylic acid amides Amino acids and derivatives Trialkylamines Azacyclic compounds Hydrocarbon derivatives Carbonyl compounds Organic oxides
• Molecular Framework: Aromatic heteropolycyclic compounds
• Substituents: N-alkylindole - 2'-aminoanilide - Indole - Indole or derivatives - Aminophenyl ether - Methoxyaniline - Anisole - Phenoxy compound - Phenol ether - Tertiary aliphatic/aromatic amine - N-arylamide - Dialkylarylamine - Aniline or substituted anilines - Methoxybenzene - Alkyl aryl ether - Aminopyrimidine - N-methylpyrrole - Pyrimidine - Substituted pyrrole - Acrylic acid or derivatives - Heteroaromatic compound - Pyrrole - Carboxamide group - Tertiary aliphatic amine - Amino acid or derivatives - Tertiary amine - Secondary carboxylic acid amide - Carboxylic acid derivative - Ether - Organoheterocyclic compound - Azacycle - Organic oxide - Organic nitrogen compound - Carbonyl group - Organic oxygen compound - Amine - Organonitrogen compound - Organooxygen compound - Hydrocarbon derivative - Aromatic heteropolycyclic compound
• Description: This compound belongs to the class of organic compounds known as 2'-aminoanilides. These are organic compounds containing an anilide moieties that carries an amino group at the 2-position of the benzene ring.
• External Descriptors: Not available

Data sources

1. Djoumbou Feunang Y, Eisner R, Knox C, Chepelev L, Hastings J, Owen G, Fahy E, Steinbeck C, Subramanian S, Bolton E, Greiner R, and Wishart DS. ClassyFire: Automated Chemical Classification With A Comprehensive, Computable Taxonomy. Journal of Cheminformatics, 2016, 8:61.

DOI: 10.1186/s13321-016-0174-y