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Osimertinib (AZD9291)

別名: Mereletinib 中文名稱：

Osimertinib (AZD9291, Mereletinib)是口服不可逆的，突變選擇性EGFR抑制劑，在 LoVo細(xì)胞中對Exon 19 缺失的 EGFR，L858R/T790M EGFR，和 WT EGFR的IC50分別為12.92，11.44 和 493.8 nM。Phase 3。

Osimertinib (AZD9291) Chemical Structure

Osimertinib (AZD9291) Chemical Structure

CAS: 1421373-65-0

規(guī)格 價格 庫存 購買數(shù)量
10mM (1mL in DMSO) 647.05 現(xiàn)貨
5mg 573.71 現(xiàn)貨
100mg 2375.99 現(xiàn)貨
1g 7944.3 現(xiàn)貨
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常與Osimertinib (AZD9291)一起在實(shí)驗(yàn)中被使用的化合物

Afatinib

兩者都是 EGFR 抑制劑。 他們的聯(lián)合療法比單獨(dú)療法對幾種 EGFR 外顯子 20 插入突變產(chǎn)生更有效的抑制作用。

Hasegawa H, et al. Lung Cancer. 2019 Jan;127:146-152.

Gefitinib

兩者都是 EGFR 抑制劑。 他們的聯(lián)合療法用于治療攜帶 T790M 和 C797S 突變的非小細(xì)胞肺癌患者。

Arulananda S, et al. J Thorac Oncol. 2017 Nov;12(11):1728-1732.

Erlotinib

兩者都是 EGFR 抑制劑。 奧希替尼（Osmiertinib）與厄洛替尼（erlotinib）聯(lián)合用于治療對第一代和第二代 TKI 耐藥的非小細(xì)胞肺癌患者。

Trametinib (GSK1120212)

奧希替尼和曲美替尼與達(dá)拉非尼一起可以克服 BRAF V600E 誘導(dǎo)的攜帶 BRAF V600E、EGFR 19del 和 T790M 突變的患者對奧希替尼耐藥。

Huang Y, et al. Journal of Thoracic Oncology 14.10 (2019): e236-e237.

Lazertinib

Lazertinib 與 Amivantamab 聯(lián)合用于治療奧希替尼復(fù)發(fā)、未接受化療的 EGFR 突變體 (EGFRm) 非小細(xì)胞肺癌。 它也被用作反應(yīng)的潛在生物標(biāo)志物。

Bauml J, et al. Journal of Clinical Oncology 39, no. 15_suppl (May 20, 2021) 9006-9006.

Osimertinib (AZD9291)相關(guān)產(chǎn)品

相關(guān)信號通路圖

EGFR Signaling Pathways

EGFR信號通路圖

細(xì)胞實(shí)驗(yàn)數(shù)據(jù)示例

細(xì)胞系 實(shí)驗(yàn)類型 給藥濃度 孵育時間 活性描述 文獻(xiàn)信息
VP-2 Growth Inhibition Assay 50 nM 10 d inhibits proliferation in long-term (10-day) growth inhibition assays 25477325
PC-9/ERc1 Growth Inhibition Assay 50 nM 10 d inhibits proliferation in long-term (10-day) growth inhibition assays 25477325
PC-9/BRc1 Growth Inhibition Assay 50 nM 10 d inhibits proliferation in long-term (10-day) growth inhibition assays 25477325
VP-2 Function Assay 50 nM 24 h induces expression of the proapoptotic BCL-2 family member BIM 25477325
PC-9/ERc1 Function Assay 50 nM 24 h induces expression of the proapoptotic BCL-2 family member BIM 25477325
PC-9/BRc1 Function Assay 50 nM 24 h induces expression of the proapoptotic BCL-2 family member BIM 25477325
PC9 GR4 Function Assay 0-10 μM 72 h inhibits?EGFR phosphorylation and downstream signaling? 25948633
PC9 Function Assay 0-10 μM 72 h inhibits WT EGFR at low concentrations 25948633
PC9 GR4 Growth Inhibition Assay 0-10 μM 72 h inhibits cell growth dose dependently 25948633
BAF3 Function assay 72 h GI50 = 0.0003 μM 28282122
BAF3 Function assay 72 h GI50 = 0.0003 μM 28282122
BAF3 Function assay 72 h GI50 = 0.001 μM 28282122
HCC827 Function assay 72 h GI50 = 0.001 μM 28282122
PC9 Function assay 72 h GI50 = 0.002 μM 28282122
BAF3 Function assay 4 h EC50 = 0.002 μM 28282122
HCC827 Function assay 3 h IC50 = 0.0025 μM 27433829
H1975 Function assay 3 h IC50 = 0.0025 μM 27433829
H3255 Function assay 3 h IC50 = 0.0041 μM 27433829
NCI-H1975 Function assay 72 h GI50 = 0.005 μM 28282122
PC9 Antiproliferative activity assay 72 h IC50 = 0.0065 μM 28716641
NCI-H1975 Antiproliferative activity assay 72 h IC50 = 0.0105 μM 28716641
PC9-DRH Function assay 2 h IC50 = 0.013 μM 26756222
BAF3 Function assay 72 h GI50 = 0.013 μM 28282122
HCC827 Function assay 96 h EC50 = 0.014 μM 28225269
HCC827 Antiproliferative activity assay 96 h EC50 = 0.014 μM 28853575
NCI-H1975 Antiproliferative activity assay 96 h EC50 = 0.014 μM 28853575
NCI-H1975 Function assay 2 h IC50 = 0.015 μM 26756222
H1975 Function assay 2 h IC50 = 0.015 μM 26968253
PC9 Function assay 2 h IC50 = 0.017 μM 26968253
NCI-H1975 Antiproliferative activity assay 72 h IC50 = 0.019 μM 29466773
NCI-H1975 Function assay 96 h EC50 = 0.019 μM 28225269
NCI-H1975 Antiproliferative activity assay 96 h EC50 = 0.019 μM 28603991
NCI-H1975 Antiproliferative activity assay 72 h IC50 = 0.019 μM 29853340
HCC827 Function assay 2 h IC50 = 0.023 μM 26756222
NCI-H1975 Antiproliferative activity assay 72 h IC50 = 0.023 μM 29534926
PC9 Cytotoxicity assay 72 h GI50 = 0.023 μM 25271963
NCI-H1975 Cytotoxicity assay 72 h GI50 = 0.024 μM 25271963
HCC827 Antiproliferative activity assay 72 h IC50 = 0.0254 μM 29576272
HCC827 Antiproliferative activity assay 72 h IC50 = 0.027 μM 29466773
HCC827 Antiproliferative activity assay 72 h IC50 = 0.027 μM 29853340
NCI-H1975 Antiproliferative activity assay 72 h IC50 = 0.03 μM 28033579
H3255 Function assay 72 h GI50 = 0.033 μM 28282122
H3255 Function assay 2 h IC50 = 0.036 μM 26756222
NCI-H1975 Antiproliferative activity assay 72 h IC50 = 0.041 μM 29730192
NCI-H1975 Function assay 1 h IC50 = 0.041 μM 29534926
BAF3 Function assay 4 h EC50 = 0.043 μM 28282122
NCI-H1975 Antiproliferative activity assay 72 h IC50 = 0.0472 μM 29576272
NCI-H1975 Antiproliferative activity assay 72 h IC50 = 0.052 μM 27131639
PC9 Function assay 2 h IC50 = 0.056 μM 26756222
NCI-H1975 Cytotoxicity assay 72 h IC50 = 0.06 μM 29486953
HaCaT Function assay 3 h IC50 = 0.0737 μM 27433829
NCI-H1975 Antiproliferative activity assay 72 h IC50 = 0.13 μM 30429956
A431 Function assay 1 h IC50 = 0.141 μM 29534926
Calu3 Cytotoxicity assay 72 h GI50 = 0.264 μM 25271963
Sf9 Function assay 20 mins IC50 = 0.278 μM 28482151
BAF3 Function assay 72 h GI50 = 0.3 μM 28282122
BAF3 Function assay 72 h GI50 = 0.31 μM 28282122
NCI-H460 Antiproliferative activity assay 72 h IC50 = 0.4159 μM 28716641
LoVo Function assay 2 h IC50 = 0.48 μM 26968253
LoVo Function assay 2 h IC50 = 0.48 μM 27996267
A549 Antiproliferative activity assay 72 h IC50 = 0.486 μM 29576272
BAF3 Function assay 72 h GI50 = 0.5 μM 28282122
A549 Antiproliferative activity assay 72 h IC50 = 0.53 μM 29466773
A549 Cytotoxicity assay 72 h IC50 = 0.53 μM 29853340
BAF3 Function assay 72 h GI50 = 0.55 μM 28282122
BAF3 Function assay 72 h GI50 = 0.56 μM 28282122
BAF3 Function assay 72 h GI50 = 0.59 μM 28282122
HT-29 Cytotoxicity assay 72 h IC50 = 0.65 μM 29486953
A431 Function assay 96 h EC50 = 0.667 μM 28225269
A431 Antiproliferative activity assay 96 h EC50 = 0.67 μM 28853575
A431 Antiproliferative activity assay 72 h IC50 = 0.685 μM 29534926
A431 Antiproliferative activity assay 96 h EC50 = 0.7 μM 28603991
A549 Cytotoxicity assay 72 h IC50 = 0.87 μM 29486953
A431 Antiproliferative activity assay 72 h IC50 = 0.893 μM 27131639
BA/F3 Antiproliferative activity assay 72 h IC50 = 1 μM 26258521
BAF3 Growth inhibition assay 72 h GI50 = 1.2 μM 28282122
NCI-H2122 Function assay 72 h GI50 = 1.2 μM 28282122
A431 Antiproliferative activity assay 72 h IC50 = 1.24 μM 30429956
A431 Antiproliferative activity assay 72 h IC50 = 1.26 μM 29730192
A431 Antiproliferative activity assay 72 h IC50 = 1.604 μM 28033579
A549 Antiproliferative activity assay 96 h EC50 = 1.83 μM 28853575
CHL Growth inhibition assay 72 h GI50 = 2.9 μM 28282122
H1355 Function assay 72 h GI50 = 3 μM 28282122
H1703 Function assay 72 h GI50 = 3.5 μM 28282122
A549 Function assay 72 h GI50 = 3.5 μM 28282122
CHO Growth inhibition assay 72 h GI50 = 4.2 μM 28282122
BAF3 Antiproliferative activity assay 72 h IC50 = 4.61 μM 30429956
BAF3 Antiproliferative activity assay 72 h IC50 = 5.15 μM 30429956
BEAS2B Antiproliferative activity assay 72 h IC50 = 14.9 μM 28716641
NCI-H1975 Function assay 2 h IC50 = 15 μM 25271963
PC9 Function assay 2 h IC50 = 17 μM 25271963
LoVo Function assay 2 h IC50 = 480 μM 25271963
HCC827 Antiproliferative activity assay 72 h Antiproliferative activity against human HCC827 cells at 1 uM after 72 hrs by MTT assay relative to control 29576272
BAF3 Function assay 2 h Inhibition of EGFR T790M/L858R/C797S mutant (unknown origin) expressed in mouse BAF3 cells assessed as reduction in EGF-induced receptor phosphorylation at 1 to 3 uM preincubated for 2 hrs followed by EGF stimulation for 15 mins by Western blot analysis 30429956
BAF3 Function assay 2 h Inhibition of EGFR 19D/T790M/C797S mutant (unknown origin) expressed in mouse BAF3 cells assessed as reduction in EGF-induced receptor phosphorylation at 1 to 3 uM preincubated for 2 hrs followed by EGF stimulation for 15 mins by Western blot analysis 30429956
Caco2 Function assay 2 h Efflux ratio of apparent permeability from basolateral side to apical side over apical side to basolateral side over in human Caco2 cells at 5 uM incubated for 2 hrs 28853575
Caco2 Function assay 2 h Apparent permeability across apical to basolateral side in human Caco2 cells at 5 uM incubated for 2 hrs 28853575
Caco2 Function assay 2 h Apparent permeability across basolateral to apical side in human Caco2 cells at 5 uM incubated for 2 hrs 28853575
NCI-H1975 Function assay 4 h Inhibition of EGFR L858R/T790M mutant in human NCI-H1975 cells assessed as reduction in Akt phosphorylation at Thr308/Ser473 site at 1 uM measured after 4 hrs by Western blot analysis 28282122
HCC827 Function assay 4 h Inhibition of EGFR exon 19 deletion mutant in human HCC827 cells assessed as reduction in Akt phosphorylation at Thr308/Ser473 site at 1 uM measured after 4 hrs by Western blot analysis 28282122
NCI-H1975 Apoptosis assay 48 h Induction of apoptosis in human NCI-H1975 cells harboring EGFR L858R/T790M mutant assessed as caspase3 cleavage at 1 uM after 48 hrs by immunoblotting 28282122
HCC827 Apoptosis assay 48 h Induction of apoptosis in human HCC827 cells harboring EGFR exon 19 deletion mutant assessed as caspase-3 cleavage at 1 uM after 48 hrs by immunoblotting 28282122
PC9 Apoptosis assay 48 h Induction of apoptosis in human PC9 cells harboring EGFR exon 19 deletion mutant assessed as caspase-3 cleavage at 1 uM after 48 hrs by immunoblotting 28282122
H3255 Apoptosis assay 48 h Induction of apoptosis in human H3255 cells harboring EGFR L858R mutant assessed as caspase-3 cleavage at 1 uM after 48 hrs by immunoblotting 28282122
NCI-H1975 Apoptosis assay 48 h Induction of apoptosis in human NCI-H1975 cells harboring EGFR L858R/T790M mutant assessed as PARP cleavage at 1 uM after 48 hrs by immunoblotting 28282122
PC9 Apoptosis assay 48 h Induction of apoptosis in human PC9 cells harboring EGFR exon 19 deletion mutant assessed as PARP cleavage at 1 uM after 48 hrs by immunoblotting 28282122
HCC827 Apoptosis assay 48 h Induction of apoptosis in human HCC827 cells harboring EGFR exon 19 deletion mutant assessed as PARP cleavage at 1 uM after 48 hrs by immunoblotting 28282122
H3255 Apoptosis assay 48 h Induction of apoptosis in human H3255 cells harboring EGFR L858R mutant assessed as PARP cleavage at 1 uM after 48 hrs by immunoblotting 28282122
Sf21 Function assay IC50 = 0.012 μM 27996267
HCC827 Antiproliferative activity assay IC50 = 0.0616 μM 28426996
NCI-H1975 Antiproliferative activity assay IC50 = 0.067 μM 28426996
A549 Function assay IC50 = 0.15 μM 26756222
HEK293 Function assay IC50 = 0.57 μM 28426996
A431 Antiproliferative activity assay IC50 = 0.6156 μM 28426996
NCI-H1975 Antitumor activity assay Antitumor activity against human NCI-H1975 cells harboring EGFR L858R/T970M double mutant xenografted in SCID mouse assessed as tumor growth inhibition at 2.5 mg/kg/day, po qd for 7 days relative to control 25271963
rat hepatocytes Function assay Intrinsic clearance in rat hepatocytes measured per 10'6 cells 25271963
human hepatocytes Function assay Intrinsic clearance in human hepatocytes measured per 10'6 cells 25271963
NCI-H1975 Antitumor activity assay Antitumor activity against human NCI-H1975 cells harboring EGFR L858R/T970M double mutant xenografted in SCID mouse assessed as tumor growth inhibition at 5 mg/kg/day, po qd for 7 days relative to control 25271963
NCI-H1975 Function assay Selectivity index, ratio of IC50 for EGFR T790M/L858R double mutant expressing human NCI-H1975 cells to IC50 for wild type EGFR expressing human A431 cells 29730192
NCI-H1975 Antitumor activity assay Antitumor activity against EGFR T790M/L858R double mutant expressing human NCI-H1975 cells xenografted in BALB/c athymic nude mouse assessed as tumor growth inhibition at 10 mg/kg, po bid for 21 days 29730192
HCC827 Apoptosis assay Induction of apoptosis in human HCC827 cells harboring EGFR E746-A750 deletion mutant assessed as early apoptotic cells at 3 uM after 24 hrs by Annexin V-FITC/propidium iodide staining based flow cytometry (Rvb = 1.34%) 29466773
HCC827 Apoptosis assay Induction of apoptosis in human HCC827 cells harboring EGFR E746-A750 deletion mutant assessed as late apoptotic cells at 3 uM after 24 hrs by Annexin V-FITC/propidium iodide staining based flow cytometry (Rvb = 27.14%) 29466773
A549 Function assay Selectivity ratio of IC50 for human A549 cells expressing wild-type EGFR/K-Ras mutant to IC50 for human NCI-H1975 cells expressing EGFR L858R/T790M double mutant 29486953
NCI-H1975 Antitumor activity assay Antitumor activity against human NCI-H1975 cells xenografted in STOCK-Foxn1nu/Nju nude mouse assessed as inhibition of tumor growth at 20 mg/kg/day, po qd for 14 days relative to untreated control 28395219
A431 Function assay Selectivity ratio of EC50 for human A431 cells expressing wild type EGFR to EC50 for human NCI-H1975 cells harboring EGFR-L858R/T790M double mutant 28853575
NCI-H1975 Function assay Selectivity ratio of IC50 for human NCI-H1975 cells harboring EGFR L858R/T790M double mutant to IC50 for human A431 cells harboring wild-type EGFR 28426996
human hepatocytes Function assay Intrinsic clearance in human hepatocytes assessed per million cells 28426996
rat hepatocytes Function assay Intrinsic clearance in rat hepatocytes assessed per million cells 28426996
A549, NCI-H1975 Function assay Selectivity ratio of IC50 for EGF-stimulated wild type EGFR in human A549 cells to IC50 for EGFR L858R/T790M double mutant in human NCI-H1975 cells 26756222
A549, PC9 Function assay Selectivity ratio of IC50 for EGF-stimulated wild type EGFR in human A549 cells to IC50 for EGFR deletion mutant in human PC9 cells 26756222
HCC827 Apoptosis assay Induction of apoptosis in human HCC827 cells harboring EGFR E746 to A750 deletion mutant assessed as early apoptotic cells at 3 uM after 24 hrs by Annexin V-FITC/propidium iodide staining based flow cytometry (Rvb = 1.34 to 1.67%) 29853340
NCI-H1975 Function assay Inhibition of EGFR L858R/T790M double mutant phosphorylation in EGF-stimulated human NCI-H1975 cells at 1 to 100 nM by Western blot method 29906114
A431 Function assay Selectivity ratio, ratio IC50 for human A431 cells overexpressing wild-type EGFR to IC50 for human NCI-H1975 cells expressing EGFR T790M/L858R mutant 27131639
PC9 Antitumor activity assay Antitumor activity against human PC9 cells harboring EGFR exon 19 deletion activating mutant xenografted in SCID mouse assessed as tumor growth inhibition at 10 mg/kg/day, po qd for 7 days relative to control 25271963
A431 Antitumor activity assay Antitumor activity against human A431 cells xenografted in SCID mouse assessed as tumor growth inhibition at 5 mg/kg/day, po qd for 7 days relative to control 25271963
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生物活性

產(chǎn)品描述 Osimertinib (AZD9291, Mereletinib)是口服不可逆的，突變選擇性EGFR抑制劑，在 LoVo細(xì)胞中對Exon 19 缺失的 EGFR，L858R/T790M EGFR，和 WT EGFR的IC50分別為12.92，11.44 和 493.8 nM。Phase 3。
靶點(diǎn)
L858R/T790M EGFR [1]
(LoVo cells)		 Exon 19 deletion EGFR [1]
(LoVo cells)		 WT EGFR [1]
(LoVo cells)
11.44 nM 12.92 nM 493.8 nM
體外研究(In Vitro)
體外研究活性

與體外野生型相比，在突變EGFR 細(xì)胞系中AZD9291能更有效的抑制增殖。[2]
實(shí)驗(yàn)圖片 檢測方法 檢測指標(biāo) 實(shí)驗(yàn)圖片 PMID
Western blot p-EGFR / p-AKT / p-ERK ABCB1 28416483
Growth inhibition assay Cell viability 31043587
Immunofluorescence Ki67 / γH2AX / p16 29212784
體內(nèi)研究(In Vivo)
體內(nèi)研究活性

AZD9291（5mg / kg p.o.）引起整個EGFRm+（PC9）和EGFRm+/ T790M（H1975）腫瘤模型腫瘤中顯著的腫瘤消退，伴隨著對體內(nèi)EGFR磷酸化和下游關(guān)鍵信號通路，如AKT和ERK的顯著抑制。[2]
動物實(shí)驗(yàn) Animal Models PC9和H1975移植瘤小鼠
Dosages ~5 毫克/千克
Administration p.o.
NCT Number Recruitment Conditions Sponsor/Collaborators Start Date Phases
NCT06350097 Not yet recruiting
Non-small Cell Lung Cancer
AstraZeneca|Daiichi Sankyo
 May 16 2024 Phase 3
NCT06323148 Not yet recruiting
Lung Cancer|EGFR Gene Mutation|Minimal Residual Disease
Fudan University
 April 1 2024 Phase 3
NCT05748093 Recruiting
Non-small Cell Lung Cancer
Maastricht University Medical Center
 April 1 2024 Phase 4
NCT06206850 Not yet recruiting
Non-squamous NSCLC
Jair Bar M.D. Ph.D.|Sheba Medical Center
 January 2024 Phase 2
NCT06053099 Recruiting
Non Small Cell Lung Cancer|EGFR Activating Mutation|EGFR DEL19|EGFR L858R
Intergroupe Francophone de Cancerologie Thoracique
 January 22 2024 Not Applicable
NCT05954871 Recruiting
Colorectal Cancer|Non-Small Cell Lung Cancer
Genentech Inc.
 January 8 2024 Phase 1

化學(xué)信息&溶解度

分子量 499.61 分子式

C28 H33 N7 O2
CAS號 1421373-65-0 SDF Download Osimertinib (AZD9291) SDF
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
儲存條件(自收到貨起)

體外溶解度
批次：

DMSO : 99 mg/mL ( (198.15 mM) ；DMSO吸濕會降低化合物溶解度，請使用新開封DMSO)

Ethanol : 99 mg/mL (198.15 mM)

Water : Insoluble

摩爾濃度計算器

體內(nèi)溶解度
批次：

現(xiàn)配現(xiàn)用，請按從左到右的順序依次添加，澄清后再加入下一溶劑

 動物體內(nèi)配方計算器

實(shí)驗(yàn)計算

摩爾濃度計算器

質(zhì)量 濃度 體積 分子量

動物體內(nèi)配方計算器（澄清溶液）

第一步：請輸入基本實(shí)驗(yàn)信息（考慮到實(shí)驗(yàn)過程中的損耗，建議多配一只動物的藥量）

mg/kg g μL 只

第二步：請輸入動物體內(nèi)配方組成（配方適用于不溶于水的藥物；不同批次藥物配方比例不同，請聯(lián)系Selleck為您提供正確的澄清溶液配方）

% DMSO % % Tween 80 % ddH2O
%DMSO %

計算結(jié)果：

工作液濃度： mg/ml；

DMSO母液配制方法： mg 藥物溶于μL DMSO溶液（母液濃度mg/mL，注：如該濃度超過該批次藥物DMSO溶解度，請先聯(lián)系Selleck）；

體內(nèi)配方配制方法：取μL DMSO母液，加入μL PEG300，混勻澄清后加入μL Tween 80，混勻澄清后加入μL ddH2O，混勻澄清。

體內(nèi)配方配制方法：取μL DMSO母液，加入μL Corn oil，混勻澄清。

注意：1. 首先保證母液是澄清的；
2.一定要按照順序依次將溶劑加入，進(jìn)行下一步操作之前必須保證上一步操作得到的是澄清的溶液，可采用渦旋、超聲或水浴加熱等物理方法助溶。

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常見問題及建議解決方法

問題 1:
Can this formulation be used in mice? What are reconstitution instructions for in vivo with mice?

回答：
Osimertinib can be used for animal study. The vehicle we suggest is: 5%DMSO+40%PEG300+5%Tween 80+50%ddH2O.

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