Osimertinib-d6

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Osimertinib-d6

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CAS NO:

1638281-44-3

AZD-9291-d6
Mereletinib-d6

Osimertinib D6 (AZD-9291 D6) 是氘标记的 Osimtinib。 Osimtinib 是一种共价结合、具有口服活性、不可逆和突变的选择性的EGFR抑制剂，其有效抑制 L858R (IC₅₀=12 nM) 和 L858R/T790M (IC₅₀=1 nM) EGFR。Osimtinib 解决了肺癌 T790M 突变介导的 EGFR 抑制剂耐药。

生物活性

Osimertinib D6 (AZD-9291 D6) is a deuterium labeled osimertinib. Osimertinib is a covalent, orally active, irreversible, and mutant-selectiveEGFRinhibitor with an apparentIC₅₀of 12 nM against L858R and 1 nM against L858R/T790M. Osimertinib overcomes T790M-mediated resistance toEGFRinhibitors in lungcancer^[1].

体外研究
(In Vitro)

Osimertinib (AZD9291) (0-10 μM; 72 hours) dramatically inhibits cell proliferation with IC₅₀s of 41, 26, 41, and 31 nM, respectively^[2].
Osimertinib (0-10 μM; 72 hours) inhibits cell proliferation (Ba/F3 cells harboring a T790M mutation, exon 19del+T790M, or L858R+T790M) with IC₅₀s of 6, 7, and 74 nM, respectively^[2].
Osimertinib (0-10 μM; 72 hours) inhibits Ba/F3 cells harboring EGFR exon 20 insertion mutations (IC₅₀ranging from 16-701 nM for A763_Y764insFQEA (FQEA), Y764_V765insHH (HH), A767_V769dupASV (ASV), and D770_N771insNPG (NPG) cells)^[2].
Osimertinib shows high levels of phenotype potency in both sensitizing-mutant (mean IC₅₀of 8 nM in PC-9) and T790M (mean IC₅₀of 11 and 40 nM in H1975 and PC-9VanR respectively) EGFR cell lines. Osimertinib has much less activity towards wild-type EGFR (mean IC₅₀of 650 and 461 nM in Calu3 and H2073 respectively)^[1].
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)^[2].

Cell Proliferation Assay^[2]

Cell 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 (IC₅₀=41,26, 41, 31 nM, respectively)

Cell Proliferation Assay^[2]

Cell 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 (IC₅₀= 6, 7, 74 nM, respectively)

Apoptosis Analysis^[2]

Cell 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 (IC₅₀= 16, 701, 230, 38 nM, respectively)

Apoptosis Analysis^[2]

Cell 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.

体内研究
(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^[1].

Animal Model:	PC-9 (ex19del) and H1975 (L858R/T790M) tumor xenograft models^[1]
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.

分子量

505.64

性状

Solid

Formula

C₂₈H₂₇D₆N₇O₂

CAS 号

1638281-44-3

中文名称

奥斯替尼 d6

运输条件

Room temperature in continental US; may vary elsewhere.

储存方式

4°C, protect from light, stored under nitrogen

*In solvent : -80°C, 6 months; -20°C, 1 month (protect from light, stored under nitrogen)