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AZD9291 (Osimertinib) Mutant-selectieve EGFR-remmer

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

Cat.nr.S7297

Osimertinib (AZD9291) is een orale, irreversibele en mutant-selectieve EGFR-remmer met een IC50 van respectievelijk 12,92, 11,44 en 493,8 nM voor Exon 19 deletie EGFR, L858R/T790M EGFR en WT EGFR in LoVo-cellen. Fase 3.

AZD9291 (Osimertinib) EGFR remmer Chemical Structure

Chemische structuur

Molecuulgewicht: 499.61

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Kwaliteitscontrole

Batch: Zuiverheid: 99.99%

99.99

Producten die vaak samen worden gebruikt met 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

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

Celkweek, behandeling & werkzame concentratie

Cellijnen	Assaytype	Concentratie	Incubatietijd	Formulering	Activiteitsbeschrijving	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
Klik om meer experimentele gegevens over cellijnen te bekijken

Chemische informatie, opslag en stabiliteit

Molecuulgewicht	499.61	Formule	C₂₈ H₃₃ N₇ O₂	Opslag (vanaf de datum van ontvangst)	3 jaar-20°Cpoeder
CAS-nr.	1421373-65-0	SDF downloaden		Opslag van stamoplossingen	1 jaar-80°Cin oplosmiddel 1 maand-20°Cin oplosmiddel
Synoniemen	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

Oplosbaarheid

In vitro
Batch:

DMSO : 99 mg/mL (198.15 mM)
(Met vocht verontreinigd DMSO kan de oplosbaarheid verminderen. Gebruik verse, watervrije DMSO.)

Ethanol : 99 mg/mL

Water : Insoluble

Molariteitscalculator

Massa	Concentratie	Volume	Molecuulgewicht
=	×	×

Verdunningscalculator Molecuulgewichtcalculator

In vivo Batch:
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 Gevalideerd door Selleck labs. Mocht u aanpassingen aan deze formulering nodig hebben, neem dan contact op met ons verkoopteam voor aangepaste 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 Gevalideerd door Selleck labs. Mocht u aanpassingen aan deze formulering nodig hebben, neem dan contact op met ons verkoopteam voor aangepaste 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 Gevalideerd door Selleck labs. Mocht u aanpassingen aan deze formulering nodig hebben, neem dan contact op met ons verkoopteam voor aangepaste 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 formulatiecalculator (heldere oplossing)

Stap 1: Voer onderstaande informatie in (Aanbevolen: een extra dier om rekening te houden met verlies tijdens het experiment)

Dosering: mg/kg Gemiddeld gewicht van dieren: g Doseervolume per dier:μL Aantal dieren:

Stap 2: Voer de in vivo formulering in (Dit is alleen de calculator, geen formulering. Neem eerst contact met ons op als er geen in vivo formulering is in de sectie oplosbaarheid.)

% DMSO + % + % Tween 80 + % ddH₂O

%DMSO+ %

Berekeningsresultaten:

Werkconcentratie: mg/ml;

Methode voor het bereiden van DMSO-moedervloeistof: mg geneesmiddel vooropgelost in μL DMSO ( Concentratie moedervloeistof mg/mL, Neem eerst contact met ons op als de concentratie de DMSO-oplosbaarheid van de batch van het geneesmiddel overschrijdt. )

Methode voor het bereiden van in vivo formulering: Neem μL DMSO moedervloeistof, voeg daarna toeμL PEG300, mengen en verhelderen, daarna toevoegenμL Tween 80, mengen en verhelderen, daarna toevoegen μL ddH₂O, mengen en verhelderen.

Methode voor het bereiden van in vivo formulering: Neem μL DMSO moedervloeistof, voeg daarna toe μL Maïsolie, mengen en verhelderen.

Opmerking: 1. Zorg ervoor dat de vloeistof helder is voordat u het volgende oplosmiddel toevoegt.
2. Zorg ervoor dat u het/de oplosmiddel(en) in de juiste volgorde toevoegt. U moet ervoor zorgen dat de verkregen oplossing, bij de vorige toevoeging, een heldere oplossing is voordat u verdergaat met het toevoegen van het volgende oplosmiddel. Fysieke methoden zoals vortexen, ultrasoon of een warmwaterbad kunnen worden gebruikt om het oplossen te bevorderen.

Werkingsmechanisme

Kenmerken	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 vertoont in vitro een significant krachtigere remming van de proliferatie in mutante EGFR-cellijnen vergeleken met wild-type.
Kinase Assay	EGFR cellulaire fosforylatie test
Kinase Assay	Cellen worden (10000 cellen/putje) geënt in groeimedium in Corning zwarte, doorzichtige 384-wells platen en 's nachts geïncubeerd bij 37°C met 5% CO₂. Cellen worden akoestisch gedoseerd met een Echo 555, waarbij de verbindingen serieel verdund zijn in 100% DMSO. Platen worden nog 2 uur geïncubeerd, waarna na aspiratie van het medium 40 μL 1x lysisbuffer aan elk putje wordt toegevoegd. Greiner zwarte high-bind 384-wells platen worden gecoat met een vangst-antilichaam en vervolgens geblokkeerd met 3% BSA. Na verwijdering van de blok, worden 15 μL van het lysaat overgebracht naar de Greiner zwarte high-bind 384-wells platen en 2 uur geïncubeerd. Na aspiratie en wassen van de platen met PBS, werden 20 μL detectie-antilichaam toegevoegd en 2 uur geïncubeerd. Na aspiratie en wassen van de platen met PBS, worden 20 μL QuantaBlu fluorogeen peroxidase substraat toegevoegd en 1 uur geïncubeerd. 20 μL QuantaBlu stopoplossing wordt aan de platen toegevoegd en fluorescentie wordt afgelezen op een Envision plaatlezer met een excitatiegolflengte van 352 nm en een emissiegolflengte van 460 nm. De verkregen gegevens met elke verbinding worden geëxporteerd naar een geschikt softwarepakket om curve-fitting analyse uit te voeren. Uit deze gegevens wordt een IC50-waarde bepaald door berekening van de concentratie van de verbinding die nodig is om een 50% effect te geven.
In vivo	AZD9291 (5 mg/kg p.o.) veroorzaakt een diepgaande regressie van tumoren in EGFRm+ (PC9) en EGFRm+/T790M (H1975) tumormodellen met een diepgaande remming van EGFR-fosforylering en belangrijke stroomafwaartse signaalroutes zoals AKT en ERK in vivo.
Referenties	[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/

Toepassingen

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

Informatie over klinische proeven

(gegevens van https://clinicaltrials.gov, bijgewerkt op 2024-05-22)

NCT-nummer	Werving	Aandoeningen	Sponsor/medewerkers	Startdatum	Fasen
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

Technische ondersteuning

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Tel: +1-832-582-8158 Ext:3

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Veelgestelde vragen

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

Antwoord:
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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