Name: AG-1478
Brand: Selleck Chemicals
SKU: S2728
Rating: 5 (101 reviews)

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Kwaliteitscontrole (Quality Control)

Batch: S272801 DMSO]25 mg/mL]false]Ethanol]13 mg/mL]false]Water]Insoluble]false Zuiverheid: 99.92%

Geciteerd in Nature Medicine vanwege de topkwaliteit
COA
NMR
HPLC
SDS
Datasheet

99.92

Gerelateerde doelwitten	VEGFR FGFR PDGFR c-Met Src MEK CSF-1R HER2 FLT3 c-Kit
Overig EGFR Inhibitoren	Lazertinib (YH25448) Icotinib Hydrochloride Sunvozertinib AG-490 Canertinib (CI-1033) Genistein Rociletinib (CO-1686) Poziotinib (NOV120101, HM781-36B) WZ4002 PD153035 HCl

Celkweek, behandeling & werkzame concentratie
(Cell Culture, Treatment & Working Concentration)

Cellijnen	Assaytype	Concentratie	Incubatietijd	Formulering	Activiteitsbeschrijving	PMID
U87MG	Growth inhibitory assay	~100 μM		DMSO	IC50=34.6 μM	8752145
U87MG.ΔEGFR	Growth inhibitory assay	~100 μM		DMSO	IC50=8.7 μM	8752145
U87MG.wtEGFR.	Growth inhibitory assay	~100 μM		DMSO	IC50=48.4 μM	8752145
U87MG	Kinase assay	~100 μM		DMSO	inhibits EGFR tyrosine kinase activity	8752145
U87MG.ΔEGFR	Kinase assay	~100 μM		DMSO	inhibits EGFR tyrosine kinase activity	8752145
U87MG.wtEGFR.	Kinase assay	~100 μM		DMSO	inhibits EGFR tyrosine kinase activity	8752145
HPV 16-immortalized human keratinocytes	Growth inhibitory assay	~50 μM		DMSO	inhibits cell growth	9288782
HPV 16-immortalized human keratinocytes	Function assay	~50 μM		DMSO	induces arrest in the Cell Cycle	9288782
HPV 16-immortalized human keratinocytes	Apoptosis assay	~50 μM		DMSO	induces apoptosis.	9288782
A431	Kinase assay	~10 μM		DMSO	inhibits the basal and TGF-α-stimulated tyrosine phosphorylation of the EGFR	10702262
MDA-468	Kinase assay	~10 μM		DMSO	inhibits the basal and TGF-α-stimulated tyrosine phosphorylation of the EGFR	10702262
A431	Function assay	~10 μM		DMSO	induces cell cycle arrest	10702262
MDA-MB-231	Kinase assay	~5 μM		DMSO	inhibits EGF stimulated phosphorylation of FKHR	11030146
CNE2	Growth inhibitory assay	100 μM		DMSO	inhibits cell proliferation by 98.4%	11410322
CNE2	Kinase assay	~100 μM		DMSO	inhibits EGFR tyrosine phosphorylation	11410322
CNE2	Function assay	~100 μM		DMSO	Inhibits MAPK and AKT activation	11410322
CNE2	Function assay	~50 μM		DMSO	affects cell cycle distribution	11410322
HSC-2	Kinase assay	8 μM		DMSO	inhibits phosphorylation of EGFR and Akt	17689285
HSC-2	Apoptosis assay	8 μM		DMSO	inhibits Fas-mediated apoptosis	17689285
HEp-2	Growth inhibitory assay	~10 μM		DMSO	enhances oridonin-induced growth-inhibitory	20202741
SubG1	Apoptosis assay	~10 μM		DMSO	enhances oridonin-induced apoptosis	20202741
HEp-2	Function assay	~10 μM		DMSO	enhances Oridonin-induced Bax activation, Bcl-2 degradation and SIRT1 inactivation	20202741
H508	Growth inhibitory assay	~1 μM		DMSO	mitigates CPF-mediated H508 cell growth	26514924
A431	Antiproliferative assay				Tested for antiproliferative activity against human A431 cells, IC50=20μM	15109642
HeLa	Function assay		30 mins		Inhibition of EGFR autophosphorylation in human HeLa cells preincubated for 30 mins prior to EGF stimulation by Western blotting	21718029
BT-37	qHTS assay				qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for BT-37 cells	29435139
SK-N-SH	qHTS assay				qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for SK-N-SH cells	29435139
NB1643	qHTS assay				qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for NB1643 cells	29435139
OHS-50	qHTS assay				qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for OHS-50 cells	29435139
HEK293	Function assay		1 hr		Inhibition of human full length PKMYT1 expressed in HEK293 cells using EFS (247 to 259 residues) as substrate after 1 hr by fluorescence polarization immunoasay, Ki=1.87μM	29941193
HEK293	Function assay		1 hr		Inhibition of human full length PKMYT1 expressed in HEK293 cells using EFS (247 to 259 residues) as substrate after 1 hr by fluorescence polarization immunoasay, IC50=19.6μM	29941193
Klik om meer experimentele gegevens over cellijnen te bekijken

Chemische informatie, opslag en stabiliteit (Chemical Information, Storage & Stability)

Molecuulgewicht	315.75	Formule	C₁₆H₁₄ClN₃O₂	Opslag (vanaf de datum van ontvangst)	3 jaar-20°Cpoeder
CAS-nr.	153436-53-4,175178-82-2	SDF downloaden		Opslag van stamoplossingen	1 jaar-80°Cin oplosmiddel 1 maand-20°Cin oplosmiddel
Synoniemen	Tyrphostin AG-1478, NSC 693255			Smiles	COC1=C(C=C2C(=C1)C(=NC=N2)NC3=CC(=CC=C3)Cl)OC

Oplosbaarheid (Solubility)

In vitro
Batch:

DMSO : 25 mg/mL (79.17 mM)
(Met vocht verontreinigd DMSO kan de oplosbaarheid verminderen. Gebruik verse, watervrije DMSO.)

Ethanol : 13 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.
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.	2.500mg/ml (7.92mM)	Taking the 1 mL working solution as an example, add 50 μL of 50 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.
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.	2.500mg/ml (7.92mM)	Taking the 1 mL working solution as an example, add 50 μL of 50 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 clarify; 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.

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 (Mechanism of Action)

Targets/IC₅₀/Ki	EGFR (Cell-free assay) 3 nM
In vitro	AG-1478 is high selective over ErbB2 and PDGFR with IC50 of >100 μM. This compound preferentially inhibits U87MG cells expressing truncated EGFR with IC50 of 8.7 μM, compared to those expressing endogenous wt EGFR or overexpressing exogenous wt EGFR with IC50 of 34.6 μM and 48.4 μM, respectively, and inhibits the DNA synthesis with IC50 of 4.6 μM, 19.67 μM, and 35.2 μM, respectively. This chemical also preferentially inhibits the tyrosine kinase activity and autophosphorylation of the ΔEGFR compared to endogenous or overexpressed exogenous wt EGFR. It (0.25 μM) abolishes the MAPK activation induced by Ang II, a Ca2+ ionophore as well as EGF but not by a phorbol ester or platelet-derived growth factor-BB in the VSMC. This compound inhibits EGF-induced mitogenesis of the BaF/ERX and LIM1215 cells with IC50 of 0.07 μM and 0.2 μM, respectively. It is able to inhibit the function of ATP-binding cassette (ABC) transporters such as ABCB1 and ABCG2, with a more pronounced effect on ABCG2.
In vivo	Administration of AG-1478 blocks phosphorylation of the EGFR at the tumor site and inhibits the growth of A431 xenografts that overexpress the WT EGFR and glioma xenografts expressing the de2-7 EGFR. Even subtherapeutic doses of this compound significantly enhance the efficacy of cytotoxic drugs, with the combination of this chemical displaying synergistic antitumor activity against human glioma xenografts. The combination of this compound and an anti-EGFR antibody (mAb 806) displays additive and in some cases synergistic, antitumor activity against tumor xenografts overexpressing the EGFR. The combination of this compound (0.4 mg) with a single dose of 25 μCi ⁹⁰Y-CHX-A''-DTPA-hu3S193 results in a significant enhancement of efficacy compared with either agent alone.
Referenties	[1] https://pubmed.ncbi.nlm.nih.gov/7892601/ [2] https://pubmed.ncbi.nlm.nih.gov/8752145/ [3] https://pubmed.ncbi.nlm.nih.gov/9535870/ [4] https://pubmed.ncbi.nlm.nih.gov/14676326/ [5] https://pubmed.ncbi.nlm.nih.gov/16203806/ [6] https://pubmed.ncbi.nlm.nih.gov/16522318/ [7] https://pubmed.ncbi.nlm.nih.gov/19059384/ [8] https://pubmed.ncbi.nlm.nih.gov/19148526/ [9] https://pubmed.ncbi.nlm.nih.gov/21472266/

Toepassingen (Applications)

Methoden	Biomarkers	Afbeeldingen	PMID
Western blot	EGFR / Neu / p-Tyr Shc / PLC-γ1		10931950
Growth inhibition assay	Cell viability		25258648

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AG-1478 EGFR Remmer

Molecuulgewicht: 315.75

Kwaliteitscontrole (Quality Control)

Celkweek, behandeling & werkzame concentratie
(Cell Culture, Treatment & Working Concentration)

Chemische informatie, opslag en stabiliteit (Chemical Information, Storage & Stability)

Oplosbaarheid (Solubility)

Molariteitscalculator

In vivo formulatiecalculator (heldere oplossing)

Werkingsmechanisme (Mechanism of Action)

Toepassingen (Applications)

AG-1478 EGFR Remmer

Molecuulgewicht: 315.75

Kwaliteitscontrole (Quality Control)

Celkweek, behandeling & werkzame concentratie (Cell Culture, Treatment & Working Concentration)

Chemische informatie, opslag en stabiliteit (Chemical Information, Storage & Stability)

Oplosbaarheid (Solubility)

Molariteitscalculator

In vivo formulatiecalculator (heldere oplossing)

Werkingsmechanisme (Mechanism of Action)

Toepassingen (Applications)

Celkweek, behandeling & werkzame concentratie
(Cell Culture, Treatment & Working Concentration)