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AZD9291 (Osimertinib) Mutantenselektiver EGFR-Inhibitor

Name: AZD9291 (Osimertinib)
Brand: Selleck Chemicals
SKU: S7297
Rating: 5 (453 reviews)

Kat.-Nr.S7297

Osimertinib (AZD9291) ist ein oraler, irreversibler und mutantenselektiver EGFR-Inhibitor mit einer IC50 von 12,92, 11,44 und 493,8 nM für Exon 19-Deletion EGFR, L858R/T790M EGFR bzw. WT EGFR in LoVo-Zellen. Phase 3.

AZD9291 (Osimertinib) EGFR Inhibitor Chemical Structure

Chemische Struktur

Molekulargewicht: 499.61

Springe zu

Qualitätskontrolle

Charge: Reinheit: 99.99%

99.99

Produkte, die oft zusammen verwendet werden mit AZD9291 (Osimertinib)

Lazertinib (YH25448)

Lazertinib in combination with Amivantamab are used for the treatment of this compound-relapsed, chemotherapy-naïve EGFR mutant (EGFRm) non-small cell lung cancer. It is also used as potenial biomarker for response

Verwandte Ziele	VEGFR PDGFR FGFR c-Met Src MEK CSF-1R FLT3 HER2 c-Kit
Weitere EGFR Inhibitoren	Icotinib Hydrochloride Sunvozertinib AG-490 AG-1478 Canertinib (CI-1033) WZ4002 Rociletinib (CO-1686) Poziotinib (NOV120101, HM781-36B) Genistein Allitinib tosylate

Zellkultur, Behandlung & Arbeitskonzentration

Zelllinien	Assay-Typ	Konzentration	Inkubationszeit	Formulierung	Aktivitätsbeschreibung	PMID
PC-9/BRc1	Function Assay	50 nM	24 h	DMSO	induces expression of the proapoptotic BCL-2 family member BIM	25477325
PC-9/ERc1	Function Assay	50 nM	24 h	DMSO	induces expression of the proapoptotic BCL-2 family member BIM	25477325
VP-2	Function Assay	50 nM	24 h	DMSO	induces expression of the proapoptotic BCL-2 family member BIM	25477325
PC-9/BRc1	Growth Inhibition Assay	50 nM	10 d	DMSO	inhibits proliferation in long-term (10-day) growth inhibition assays	25477325
PC-9/ERc1	Growth Inhibition Assay	50 nM	10 d	DMSO	inhibits proliferation in long-term (10-day) growth inhibition assays	25477325
VP-2	Growth Inhibition Assay	50 nM	10 d	DMSO	inhibits proliferation in long-term (10-day) growth inhibition assays	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
Sf21	Function assay				IC50 = 0.012 μM	27996267
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
HCC827	Antiproliferative activity assay				IC50 = 0.0616 μM	28426996
NCI-H1975	Antiproliferative activity assay				IC50 = 0.067 μM	28426996
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
A549	Function assay				IC50 = 0.15 μM	26756222
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
HEK293	Function assay				IC50 = 0.57 μM	28426996
BAF3	Function assay		72 h		GI50 = 0.59 μM	28282122
A431	Antiproliferative activity assay				IC50 = 0.6156 μM	28426996
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
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
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
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
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
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
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
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
Klicken Sie hier, um weitere experimentelle Daten zu Zelllinien anzuzeigen

Chemische Informationen, Lagerung & Stabilität

Molekulargewicht	499.61	Formel	C₂₈ H₃₃ N₇ O₂	Lagerung (Ab dem Eingangsdatum)	3 Jahre-20°CPulver
CAS-Nr.	1421373-65-0	SDF herunterladen		Lagerung von Stammlösungen	1 Jahr-80°Cin Lösungsmittel 1 Monat-20°Cin Lösungsmittel
Synonyme	Mereletinib			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

Löslichkeit

In vitro
Charge:

DMSO : 99 mg/mL (198.15 mM)
(Feuchtigkeitskontaminiertes DMSO kann die Löslichkeit verringern. Verwenden Sie frisches, wasserfreies DMSO.)

Ethanol : 99 mg/mL

Water : Insoluble

DMSO : 100 mg/mL (200.15 mM)
(Feuchtigkeitskontaminiertes DMSO kann die Löslichkeit verringern. Verwenden Sie frisches, wasserfreies DMSO.)

Ethanol : 33 mg/mL

Water : Insoluble

DMSO : 100 mg/mL (200.15 mM)
(Feuchtigkeitskontaminiertes DMSO kann die Löslichkeit verringern. Verwenden Sie frisches, wasserfreies DMSO.)

Ethanol : 100 mg/mL

Water : Insoluble

DMSO : 100 mg/mL (200.15 mM)
(Feuchtigkeitskontaminiertes DMSO kann die Löslichkeit verringern. Verwenden Sie frisches, wasserfreies DMSO.)

Ethanol : 25 mg/mL

Water : Insoluble

DMSO : 99 mg/mL (198.15 mM)
(Feuchtigkeitskontaminiertes DMSO kann die Löslichkeit verringern. Verwenden Sie frisches, wasserfreies DMSO.)

Ethanol : 36 mg/mL

Water : Insoluble

Molaritätsrechner

Masse	Konzentration	Volumen	Molekulargewicht
=	×	×

Verdünnungsrechner Molekulargewichtsrechner

In vivo Charge:
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Clear solution	5%DMSO 1 40%PEG300 2 5%Tween80 3 50%ddH2O Von Selleck Labs validiert. Sollten Sie Anpassungen an dieser Formulierung benötigen, kontaktieren Sie unser Verkaufsteam für kundenspezifische Tests.	7.500mg/ml (15.01mM)	Taking the 1 mL working solution as an example, add 50 μL of 150 mg/ml clarified DMSO stock solution to 400 μL of PEG300, mix evenly to clarify it; add 50 μL of Tween80 to the above system, mix evenly to make it clear; then continue to add 500 μL of ddH2O to adjust the volume to 1 mL. The mixed solution should be used immediately for optimal results.
Clear solution	5% DMSO 1 95% Corn oil Von Selleck Labs validiert. Sollten Sie Anpassungen an dieser Formulierung benötigen, kontaktieren Sie unser Verkaufsteam für kundenspezifische Tests.	0.800mg/ml (1.60mM)	Taking the 1 mL working solution as an example, add 50 μL of 16 mg/ml clear DMSO stock solution to 950 μL of corn oil and mix evenly. The mixed solution should be used immediately for optimal results.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Clear solution	5%DMSO 1 Corn oil Von Selleck Labs validiert. Sollten Sie Anpassungen an dieser Formulierung benötigen, kontaktieren Sie unser Verkaufsteam für kundenspezifische Tests.	5.000mg/ml (10.01mM)	Taking the 1 mL working solution as an example, add 50 μL of 100 mg/ml clear DMSO stock solution to 950 μL of corn oil and mix evenly. The mixed solution should be used immediately for optimal results.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.

In-vivo-Formulierungsrechner (Klare Lösung)

Schritt 1: Geben Sie die untenstehenden Informationen ein (Empfohlen: Ein zusätzliches Tier zur Berücksichtigung von Verlusten während des Experiments)

Dosierung: mg/kg Durchschnittsgewicht der Tiere: g Dosiervolumen pro Tier:μL Anzahl der Tiere:

Schritt 2: Geben Sie die In-vivo-Formulierung ein (Dies ist nur der Rechner, keine Formulierung. Bitte kontaktieren Sie uns zuerst, wenn es im Abschnitt "Löslichkeit" keine In-vivo-Formulierung gibt.)

% DMSO + % + % Tween 80 + % ddH₂O

%DMSO+ %

Berechnungsergebnisse:

Arbeitskonzentration: mg/ml;

Methode zur Herstellung der DMSO-Stammlösung: mg Wirkstoff vorgelöst in μL DMSO ( Konzentration der Stammlösung mg/mL, Bitte kontaktieren Sie uns zuerst, wenn die Konzentration die DMSO-Löslichkeit der Wirkstoffcharge überschreitet. )

Methode zur Herstellung der In-vivo-Formulierung: Nehmen Sie μL DMSO Stammlösung, dann hinzufügenμL PEG300, mischen und klären, dann hinzufügenμL Tween 80, mischen und klären, dann hinzufügen μL ddH₂O, mischen und klären.

Methode zur Herstellung der In-vivo-Formulierung: Nehmen Sie μL DMSO Stammlösung, dann hinzufügen μL Maisöl, mischen und klären.

Hinweis: 1. Bitte stellen Sie sicher, dass die Flüssigkeit klar ist, bevor Sie das nächste Lösungsmittel hinzufügen.
2. Achten Sie darauf, das/die Lösungsmittel der Reihe nach hinzuzufügen. Sie müssen sicherstellen, dass die bei der vorherigen Zugabe erhaltene Lösung eine klare Lösung ist, bevor Sie mit der Zugabe des nächsten Lösungsmittels fortfahren. Physikalische Methoden wie Vortex, Ultraschall oder ein heißes Wasserbad können zur Unterstützung des Lösens verwendet werden.

Wirkmechanismus

Merkmale	Orally bioavailable mutant-selective EGFR inhibitor that has been tested in Phase III clinical trials for treatment of Non-Small Cell Lung Cancer.
Targets/IC₅₀/Ki	L858R/T790M EGFR (LoVo cells) 11.44 nM Exon 19 deletion EGFR (LoVo cells) 12.92 nM WT EGFR (LoVo cells) 493.8 nM
In vitro	AZD9291 zeigt in vitro eine signifikant potentere Hemmung der Proliferation in mutierten EGFR-Zelllinien im Vergleich zum Wildtyp.
Kinase-Assay	EGFR-Zellphosphorylierungsassay
Kinase-Assay	Zellen werden (10000 Zellen/Well) in Wachstumsmedium in schwarzen Corning 384-Well-Platten mit klarem Boden ausgesät und über Nacht bei 37 °C mit 5 % CO₂ inkubiert. Die Zellen werden akustisch unter Verwendung eines Echo 555 dosiert, wobei die Verbindungen in 100 % DMSO seriell verdünnt werden. Die Platten werden für weitere 2 Stunden inkubiert, dann wird nach dem Absaugen des Mediums 40 μL lx Lysepuffer zu jedem Well gegeben. Schwarze Greiner High-Bind-384-Well-Platten werden mit Fangantikörper beschichtet und dann mit 3 % BSA blockiert. Nach dem Entfernen des Blocks werden 15 μL Lysat in die schwarzen Greiner High-Bind-384-Well-Platten überführt und 2 Stunden lang inkubiert. Nach dem Absaugen und Waschen der Platten mit PBS wurden 20 μL Nachweisantikörper hinzugefügt und 2 Stunden lang inkubiert. Nach dem Absaugen und Waschen der Platten mit PBS werden 20 μL QuantaBlu fluorogenes Peroxidasesubstrat hinzugefügt und 1 Stunde lang inkubiert. 20 μL QuantaBlu Stopplösung werden zu den Platten hinzugefügt und die Fluoreszenz wird auf einem Envision-Plattenlesegerät bei einer Anregungswellenlänge von 352 nm und einer Emissionswellenlänge von 460 nm abgelesen. Die mit jeder Verbindung erhaltenen Daten werden in ein geeignetes Softwarepaket exportiert, um eine Kurvenanpassungsanalyse durchzuführen. Aus diesen Daten wird ein IC50-Wert durch Berechnung der Konzentration der Verbindung bestimmt, die erforderlich ist, um einen 50%igen Effekt zu erzielen.
In vivo	AZD9291 (5 mg/kg p.o.) verursacht eine tiefgreifende Regression von Tumoren in EGFRm+ (PC9) und EGFRm+/T790M (H1975) Tumormodellen mit einer tiefgreifenden Hemmung der EGFR-Phosphorylierung und wichtiger nachgeschalteter Signalwege wie AKT und ERK in vivo.
Literatur	[1] http://www.google.com/patents/WO2013014448A1?cl=en [2] http://mct.aacrjournals.org/content/12/11_Supplement/A109 [3] https://pubmed.ncbi.nlm.nih.gov/35353542/

Anwendungen

Methoden	Biomarker	PMID
Western blot	p-EGFR / p-AKT / p-ERK ABCB1	28416483
Growth inhibition assay	Cell viability	31043587
Immunofluorescence	Ki67 / γH2AX / p16	29212784

Klinische Studieninformationen

(Daten von https://clinicaltrials.gov, aktualisiert am 2024-05-22)

NCT-Nummer	Rekrutierung	Erkrankungen	Sponsor/Kooperationspartner	Startdatum	Phasen
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

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

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

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