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Afuresertib (GSK2110183) Akt remmer

Name: Afuresertib (GSK2110183)
Brand: Selleck Chemicals
SKU: S7521
Rating: 5 (38 reviews)

Cat.nr.S7521

Afuresertib (GSK2110183) is een potente, oraal biologisch beschikbare Akt-remmer met K_i-waarden van respectievelijk 0,08 nM, 2 nM en 2,6 nM voor Akt1, Akt2 en Akt3, en bevindt zich momenteel in fase 2-onderzoeken.

Afuresertib (GSK2110183) Akt remmer Chemical Structure

Chemische structuur

Molecuulgewicht: 427.32

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Kwaliteitscontrole

Batch: Zuiverheid: 99.61%

99.61

Gerelateerde doelwitten	PI3K mTOR GSK-3 ATM/ATR DNA-PK AMPK PDPK1 PTEN PP2A PDK
Overig Akt Inhibitoren	SC79 AZD5363 (Capivasertib) MK-2206 Dihydrochloride Ipatasertib (GDC-0068) Perifosine GSK690693 Triciribine (API-2) CCT128930 A-674563 HCl Akti-1/2

Celkweek, behandeling & werkzame concentratie

Cellijnen	Assaytype	Incubatietijd	Activiteitsbeschrijving	PMID
Sf9	Function assay	40 mins	Inhibition of full length human AKT1 expressed in Sf9 cells assessed as reduction in substrate phosphorylation using biotin-ahx-ARKRERAYSFGHHA-amide substrate and [gamma-33P]ATP incubated for 40 mins by top count microplate scintillation counting method, IC50 = 0.001 μM.	ChEMBL
Sf9	Function assay	40 mins	Inhibition of full length human AKT3 expressed in Sf9 cells assessed as reduction in substrate phosphorylation using biotin-ahx-ARKRERAYSFGHHA-amide substrate and [gamma-33P]ATP incubated for 40 mins by top count microplate scintillation counting method, IC50 = 0.001585 μM.	ChEMBL
COLO205	Growth inhibition assay	72 hrs	Growth inhibition of human COLO205 cells at 1:10 molar ratio of compound in presence of N-{3-[3-cyclopropyl-5-(2-fluoro-4-iodo-phenylamino)-6,8-dimethyl- 2,4,7-trioxo-3,4,6,7-tetrahydro-2H-pyrido[4,3-d]pyrimidin-1-yl]phenyl}acetamide incubated for 72 hrs , IC50 = 0.009 μM.	ChEMBL
Sf9	Function assay	40 mins	Inhibition of full length human AKT2 expressed in Sf9 cells assessed as reduction in substrate phosphorylation using biotin-ahx-ARKRERAYSFGHHA-amide substrate and [gamma-33P]ATP incubated for 40 mins by top count microplate scintillation counting method, IC50 = 0.01 μM.	ChEMBL
MV522	Growth inhibition assay	72 hrs	Growth inhibition of human MV522 cells at 1:10 molar ratio of compound in presence of N-{3-[3-cyclopropyl-5-(2-fluoro-4-iodo-phenylamino)-6,8-dimethyl- 2,4,7-trioxo-3,4,6,7-tetrahydro-2H-pyrido[4,3-d]pyrimidin-1-yl]phenyl}acetamide incubated for 72 hrs, IC50 = 0.012 μM.	ChEMBL
HT-29	Growth inhibition assay	72 hrs	Growth inhibition of human HT-29 cells at 1:10 molar ratio of compound in presence of N-{3-[3-cyclopropyl-5-(2-fluoro-4-iodo-phenylamino)-6,8-dimethyl- 2,4,7-trioxo-3,4,6,7-tetrahydro-2H-pyrido[4,3-d]pyrimidin-1-yl]phenyl}acetamide incubated for 72 hrs, IC50 = 0.015 μM.	ChEMBL
NCI-H727	Growth inhibition assay	72 hrs	Growth inhibition of human NCI-H727 cells at 1:10 molar ratio of compound in presence of N-{3-[3-cyclopropyl-5-(2-fluoro-4-iodo-phenylamino)-6,8-dimethyl- 2,4,7-trioxo-3,4,6,7-tetrahydro-2H-pyrido[4,3-d]pyrimidin-1-yl]phenyl}acetamide incubated for 72 hrs, IC50 = 0.019 μM.	ChEMBL
SW1417	Growth inhibition assay	72 hrs	Growth inhibition of human SW1417 cells at 1:10 molar ratio of compound in presence of N-{3-[3-cyclopropyl-5-(2-fluoro-4-iodo-phenylamino)-6,8-dimethyl- 2,4,7-trioxo-3,4,6,7-tetrahydro-2H-pyrido[4,3-d]pyrimidin-1-yl]phenyl}acetamide incubated for 72 hrs, IC50 = 0.03 μM.	ChEMBL
Calu6	Growth inhibition assay	72 hrs	Growth inhibition of human Calu6 cells at 1:10 molar ratio of compound in presence of N-{3-[3-cyclopropyl-5-(2-fluoro-4-iodo-phenylamino)-6,8-dimethyl- 2,4,7-trioxo-3,4,6,7-tetrahydro-2H-pyrido[4,3-d]pyrimidin-1-yl]phenyl}acetamide incubated for 72 hrs, IC50 = 0.031 μM.	ChEMBL
LS1034	Growth inhibition assay	72 hrs	Growth inhibition of human LS1034 cells at 1:10 molar ratio of compound in presence of N-{3-[3-cyclopropyl-5-(2-fluoro-4-iodo-phenylamino)-6,8-dimethyl- 2,4,7-trioxo-3,4,6,7-tetrahydro-2H-pyrido[4,3-d]pyrimidin-1-yl]phenyl}acetamide incubated for 72 hrs, IC50 = 0.04 μM.	ChEMBL
SW1463	Growth inhibition assay	72 hrs	Growth inhibition of human SW1463 cells at 1:10 molar ratio of compound in presence of N-{3-[3-cyclopropyl-5-(2-fluoro-4-iodo-phenylamino)-6,8-dimethyl- 2,4,7-trioxo-3,4,6,7-tetrahydro-2H-pyrido[4,3-d]pyrimidin-1-yl]phenyl}acetamide incubated for 72 hrs, IC50 = 0.041 μM.	ChEMBL
RKO	Growth inhibition assay	72 hrs	Growth inhibition of human RKO cells at 1:10 molar ratio of compound in presence of N-{3-[3-cyclopropyl-5-(2-fluoro-4-iodo-phenylamino)-6,8-dimethyl- 2,4,7-trioxo-3,4,6,7-tetrahydro-2H-pyrido[4,3-d]pyrimidin-1-yl]phenyl}acetamide incubated for 72 hrs, IC50 = 0.054 μM.	ChEMBL
NCI-H508	Growth inhibition assay	72 hrs	Growth inhibition of human NCI-H508 cells at 1:10 molar ratio of compound in presence of N-{3-[3-cyclopropyl-5-(2-fluoro-4-iodo-phenylamino)-6,8-dimethyl- 2,4,7-trioxo-3,4,6,7-tetrahydro-2H-pyrido[4,3-d]pyrimidin-1-yl]phenyl}acetamide incubated for 72 hrs, IC50 = 0.08 μM.	ChEMBL
NCI-H1155	Growth inhibition assay	72 hrs	Growth inhibition of human NCI-H1155 cells at 1:10 molar ratio of compound in presence of N-{3-[3-cyclopropyl-5-(2-fluoro-4-iodo-phenylamino)-6,8-dimethyl- 2,4,7-trioxo-3,4,6,7-tetrahydro-2H-pyrido[4,3-d]pyrimidin-1-yl]phenyl}acetamide incubated for 72 hr, IC50 = 0.101 μM.	ChEMBL
A427	Growth inhibition assay	72 hrs	Growth inhibition of human A427 cells at 1:10 molar ratio of compound in presence of N-{3-[3-cyclopropyl-5-(2-fluoro-4-iodo-phenylamino)-6,8-dimethyl- 2,4,7-trioxo-3,4,6,7-tetrahydro-2H-pyrido[4,3-d]pyrimidin-1-yl]phenyl}acetamide incubated for 72 hrs, IC50 = 0.103 μM.	ChEMBL
KM12	Growth inhibition assay	72 hrs	Growth inhibition of human KM12 cells at 1:10 molar ratio of compound in presence of N-{3-[3-cyclopropyl-5-(2-fluoro-4-iodo-phenylamino)-6,8-dimethyl- 2,4,7-trioxo-3,4,6,7-tetrahydro-2H-pyrido[4,3-d]pyrimidin-1-yl]phenyl}acetamide incubated for 72 hrs, IC50 = 0.104 μM.	ChEMBL
HCT8	Growth inhibition assay	72 hrs	Growth inhibition of human HCT8 cells at 1:10 molar ratio of compound in presence of N-{3-[3-cyclopropyl-5-(2-fluoro-4-iodo-phenylamino)-6,8-dimethyl- 2,4,7-trioxo-3,4,6,7-tetrahydro-2H-pyrido[4,3-d]pyrimidin-1-yl]phenyl}acetamide incubated for 72 hrs, IC50 = 0.143 μM.	ChEMBL
MDA-MB-175-VII	Growth inhibition assay	72 hrs	Growth inhibition of human MDA-MB-175-VII cells at 1:10 molar ratio of compound in presence of N-{3-[3-cyclopropyl-5-(2-fluoro-4-iodo-phenylamino)-6,8-dimethyl- 2,4,7-trioxo-3,4,6,7-tetrahydro-2H-pyrido[4,3-d]pyrimidin-1-yl]phenyl}acetamide incubated for 72 hrs, IC50 = 0.155 μM.	ChEMBL
A549	Growth inhibition assay	72 hrs	Growth inhibition of human A549 cells at 1:10 molar ratio of compound in presence of N-{3-[3-cyclopropyl-5-(2-fluoro-4-iodo-phenylamino)-6,8-dimethyl- 2,4,7-trioxo-3,4,6,7-tetrahydro-2H-pyrido[4,3-d]pyrimidin-1-yl]phenyl}acetamide incubated for 72 hrs, IC50 = 0.164 μM.	ChEMBL
NCI-H23	Growth inhibition assay	72 hrs	Growth inhibition of human NCI-H23 cells at 1:10 molar ratio of compound in presence of N-{3-[3-cyclopropyl-5-(2-fluoro-4-iodo-phenylamino)-6,8-dimethyl- 2,4,7-trioxo-3,4,6,7-tetrahydro-2H-pyrido[4,3-d]pyrimidin-1-yl]phenyl}acetamide incubated for 72 hrs , IC50 = 0.199 μM.	ChEMBL
SW837	Growth inhibition assay	72 hrs	Growth inhibition of human SW837 cells at 1:10 molar ratio of compound in presence of N-{3-[3-cyclopropyl-5-(2-fluoro-4-iodo-phenylamino)-6,8-dimethyl- 2,4,7-trioxo-3,4,6,7-tetrahydro-2H-pyrido[4,3-d]pyrimidin-1-yl]phenyl}acetamide incubated for 72 hrs, IC50 = 0.248 μM.	ChEMBL
SW480	Growth inhibition assay	72 hrs	Growth inhibition of human SW480 cells at 1:10 molar ratio of compound in presence of N-{3-[3-cyclopropyl-5-(2-fluoro-4-iodo-phenylamino)-6,8-dimethyl- 2,4,7-trioxo-3,4,6,7-tetrahydro-2H-pyrido[4,3-d]pyrimidin-1-yl]phenyl}acetamide incubated for 72 hrs, IC50 = 0.259 μM.	ChEMBL
NCI-H1355	Growth inhibition assay	72 hrs	Growth inhibition of human NCI-H1355 cells at 1:10 molar ratio of compound in presence of N-{3-[3-cyclopropyl-5-(2-fluoro-4-iodo-phenylamino)-6,8-dimethyl- 2,4,7-trioxo-3,4,6,7-tetrahydro-2H-pyrido[4,3-d]pyrimidin-1-yl]phenyl}acetamide incubated for 72 hr, IC50 = 0.268 μM.	ChEMBL
EFM19	Growth inhibition assay	72 hrs	Growth inhibition of human EFM19 cells at 1:10 molar ratio of compound in presence of N-{3-[3-cyclopropyl-5-(2-fluoro-4-iodo-phenylamino)-6,8-dimethyl- 2,4,7-trioxo-3,4,6,7-tetrahydro-2H-pyrido[4,3-d]pyrimidin-1-yl]phenyl}acetamide incubated for 72 hrs, IC50 = 0.3 μM.	ChEMBL
T84	Growth inhibition assay	72 hrs	Growth inhibition of human T84 cells at 1:10 molar ratio of compound in presence of N-{3-[3-cyclopropyl-5-(2-fluoro-4-iodo-phenylamino)-6,8-dimethyl- 2,4,7-trioxo-3,4,6,7-tetrahydro-2H-pyrido[4,3-d]pyrimidin-1-yl]phenyl}acetamide incubated for 72 hrs, IC50 = 0.304 μM.	ChEMBL
COR-L23	Growth inhibition assay	72 hrs	Growth inhibition of human COR-L23 cells at 1:10 molar ratio of compound in presence of N-{3-[3-cyclopropyl-5-(2-fluoro-4-iodo-phenylamino)-6,8-dimethyl- 2,4,7-trioxo-3,4,6,7-tetrahydro-2H-pyrido[4,3-d]pyrimidin-1-yl]phenyl}acetamide incubated for 72 hrs , IC50 = 0.368 μM.	ChEMBL
NCI-H1792	Growth inhibition assay	72 hrs	Growth inhibition of human NCI-H1792 cells at 1:10 molar ratio of compound in presence of N-{3-[3-cyclopropyl-5-(2-fluoro-4-iodo-phenylamino)-6,8-dimethyl- 2,4,7-trioxo-3,4,6,7-tetrahydro-2H-pyrido[4,3-d]pyrimidin-1-yl]phenyl}acetamide incubated for 72 hr, IC50 = 0.374 μM.	ChEMBL
SW1573	Growth inhibition assay	72 hrs	Growth inhibition of human SW1573 cells at 1:10 molar ratio of compound in presence of N-{3-[3-cyclopropyl-5-(2-fluoro-4-iodo-phenylamino)-6,8-dimethyl- 2,4,7-trioxo-3,4,6,7-tetrahydro-2H-pyrido[4,3-d]pyrimidin-1-yl]phenyl}acetamide incubated for 72 hrs, IC50 = 0.382 μM.	ChEMBL
Calu3	Growth inhibition assay	72 hrs	Growth inhibition of human Calu3 cells at 1:10 molar ratio of compound in presence of N-{3-[3-cyclopropyl-5-(2-fluoro-4-iodo-phenylamino)-6,8-dimethyl- 2,4,7-trioxo-3,4,6,7-tetrahydro-2H-pyrido[4,3-d]pyrimidin-1-yl]phenyl}acetamide incubated for 72 hrs, IC50 = 0.392 μM.	ChEMBL
HCC827	Growth inhibition assay	72 hrs	Growth inhibition of human HCC827 cells at 1:10 molar ratio of compound in presence of N-{3-[3-cyclopropyl-5-(2-fluoro-4-iodo-phenylamino)-6,8-dimethyl- 2,4,7-trioxo-3,4,6,7-tetrahydro-2H-pyrido[4,3-d]pyrimidin-1-yl]phenyl}acetamide incubated for 72 hrs, IC50 = 0.401 μM.	ChEMBL
EFM19	Growth inhibition assay	72 hrs	Growth inhibition of human EFM19 cells incubated for 72 hrs by Cell-titer-Glo reagent based assay, IC50 = 0.43 μM.	ChEMBL
HOP62	Growth inhibition assay	72 hrs	Growth inhibition of human HOP62 cells at 1:10 molar ratio of compound in presence of N-{3-[3-cyclopropyl-5-(2-fluoro-4-iodo-phenylamino)-6,8-dimethyl- 2,4,7-trioxo-3,4,6,7-tetrahydro-2H-pyrido[4,3-d]pyrimidin-1-yl]phenyl}acetamide incubated for 72 hrs, IC50 = 0.498 μM.	ChEMBL
NCI-H508	Growth inhibition assay	72 hrs	Growth inhibition of human NCI-H508 cells incubated for 72 hrs by Cell-titer-Glo reagent based assay, IC50 = 0.522 μM.	ChEMBL
SW900	Growth inhibition assay	72 hrs	Growth inhibition of human SW900 cells at 1:10 molar ratio of compound in presence of N-{3-[3-cyclopropyl-5-(2-fluoro-4-iodo-phenylamino)-6,8-dimethyl- 2,4,7-trioxo-3,4,6,7-tetrahydro-2H-pyrido[4,3-d]pyrimidin-1-yl]phenyl}acetamide incubated for 72 hrs, IC50 = 0.719 μM.	ChEMBL
MDA-MB-175-VII	Growth inhibition assay	72 hrs	Growth inhibition of human MDA-MB-175-VII cells incubated for 72 hrs by Cell-titer-Glo reagent based assay, IC50 = 0.794 μM.	ChEMBL
NCI-H1155	Growth inhibition assay	72 hrs	Growth inhibition of human NCI-H1155 cells incubated for 72 hrs by Cell-titer-Glo reagent based assay, IC50 = 0.865 μM.	ChEMBL
DLD1	Growth inhibition assay	72 hrs	Growth inhibition of human DLD1 cells at 1:10 molar ratio of compound in presence of N-{3-[3-cyclopropyl-5-(2-fluoro-4-iodo-phenylamino)-6,8-dimethyl- 2,4,7-trioxo-3,4,6,7-tetrahydro-2H-pyrido[4,3-d]pyrimidin-1-yl]phenyl}acetamide incubated for 72 hrs, IC50 = 0.932 μM.	ChEMBL
HT-29	Growth inhibition assay	72 hrs	Growth inhibition of human HT-29 cells incubated for 72 hrs by Cell-titer-Glo reagent based assay, IC50 = 1.383 μM.	ChEMBL
HCT8	Growth inhibition assay	72 hrs	Growth inhibition of human HCT8 cells incubated for 72 hrs by Cell-titer-Glo reagent based assay, IC50 = 1.541 μM.	ChEMBL
RKO	Growth inhibition assay	72 hrs	Growth inhibition of human RKO cells incubated for 72 hrs by Cell-titer-Glo reagent based assay, IC50 = 1.806 μM.	ChEMBL
Calu6	Growth inhibition assay	72 hrs	Growth inhibition of human Calu6 cells incubated for 72 hrs by Cell-titer-Glo reagent based assay, IC50 = 2.154 μM.	ChEMBL
KM12	Growth inhibition assay	72 hrs	Growth inhibition of human KM12 cells incubated for 72 hrs by Cell-titer-Glo reagent based assay, IC50 = 2.247 μM.	ChEMBL
COLO205	Growth inhibition assay	72 hrs	Growth inhibition of human COLO205 cells incubated for 72 hrs by Cell-titer-Glo reagent based assay, IC50 = 2.567 μM.	ChEMBL
MV522	Growth inhibition assay	72 hrs	Growth inhibition of human MV522 cells incubated for 72 hrs by Cell-titer-Glo reagent based assay, IC50 = 3.044 μM.	ChEMBL
LS1034	Growth inhibition assay	72 hrs	Growth inhibition of human LS1034 cells incubated for 72 hrs by Cell-titer-Glo reagent based assay, IC50 = 4.339 μM.	ChEMBL
NCI-H727	Growth inhibition assay	72 hrs	Growth inhibition of human NCI-H727 cells incubated for 72 hrs by Cell-titer-Glo reagent based assay, IC50 = 4.799 μM.	ChEMBL
COR-L23	Growth inhibition assay	72 hrs	Growth inhibition of human COR-L23 cells incubated for 72 hrs by Cell-titer-Glo reagent based assay, IC50 = 5.373 μM.	ChEMBL
A549	Growth inhibition assay	72 hrs	Growth inhibition of human A549 cells incubated for 72 hrs by Cell-titer-Glo reagent based assay, IC50 = 5.993 μM.	ChEMBL
NCI-H1355	Growth inhibition assay	72 hrs	Growth inhibition of human NCI-H1355 cells incubated for 72 hrs by Cell-titer-Glo reagent based assay, IC50 = 6.685 μM.	ChEMBL
NCI-H23	Growth inhibition assay	72 hrs	Growth inhibition of human NCI-H23 cells incubated for 72 hrs by Cell-titer-Glo reagent based assay, IC50 = 7.124 μM.	ChEMBL
NCI-H1792	Growth inhibition assay	72 hrs	Growth inhibition of human NCI-H1792 cells incubated for 72 hrs by Cell-titer-Glo reagent based assay, IC50 = 7.307 μM.	ChEMBL
SW1463	Growth inhibition assay	72 hrs	Growth inhibition of human SW1463 cells incubated for 72 hrs by Cell-titer-Glo reagent based assay, IC50 = 9.725 μM.	ChEMBL
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Chemische informatie, opslag en stabiliteit

Molecuulgewicht	427.32	Formule	C₁₈H₁₇Cl₂FN₄OS	Opslag (vanaf de datum van ontvangst)	3 jaar-20°Cpoeder
CAS-nr.	1047644-62-1	SDF downloaden		Opslag van stamoplossingen	1 jaar-80°Cin oplosmiddel 1 maand-20°Cin oplosmiddel
Synoniemen	N/A			Smiles	CN1C(=C(C=N1)Cl)C2=C(SC(=C2)C(=O)NC(CC3=CC(=CC=C3)F)CN)Cl

Oplosbaarheid

In vitro
Batch:

DMSO : 85 mg/mL (198.91 mM)
(Met vocht verontreinigd DMSO kan de oplosbaarheid verminderen. Gebruik verse, watervrije DMSO.)

Ethanol : 85 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.

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

Targets/IC₅₀/Ki	Akt1 (Cell-free assay) 0.08 nM(Ki) Akt2 (Cell-free assay) 2 nM(Ki) Akt3 (Cell-free assay) 2.6 nM(Ki)
In vitro	Afuresertib (GSK2110183) remt de kinaseactiviteit van het E17K AKT1-mutante eiwit met een EC50 van 0,2 nM. Het vertoont een concentratie-afhankelijk effect op meerdere AKT-substraatfosforylatie-niveaus, waaronder GSK3b, PRAS40, FOXO en Caspase 9. Over het algemeen is 65% van de hematologische cellijnen gevoelig voor deze verbinding (EC50 < 1 μM). Van de geteste solide tumorcellijnen heeft 21% een EC50 < 1 μM als reactie op afuresertib.
Kinase Assay	Potentie (Ki*) van afuresertib
Kinase Assay	De ware potentie (Ki*) van Afuresertib (GSK2110183) wordt initieel bepaald bij lage enzymconcentraties (0,1 nM AKT1, 0,7 nM AKT2 en 0,2 nM AKT3) met behulp van een filterbindingsassay en vervolgens bevestigd met progressiecurve-analyse. In de filterbindingsassay wordt een voormengsel van enzym plus deze verbinding gedurende 1 uur geïncubeerd en vervolgens toegevoegd aan een GSKα-peptide (Ac-KKGGRARTSS-FAEPG-amide) en [γ³³P] ATP. Reacties worden beëindigd na 2 uur en het radiogemerkte AKT-peptideproduct wordt opgevangen in een fosfo-cellulose filterplaat. Progressiecurve-analyse maakt gebruik van continue real-time fluorescentiedetectie van productvorming met behulp van het Sox-AKT-tide-substraat (Ac-ARKRERAYSF-d-Pro-Sox-Gly-NH2).
In vivo	Afuresertib (GSK2110183) werd oraal toegediend in doses van 10, 30 of 100 mg/kg dagelijks aan muizen met BT474 borsttumorxenografts, wat resulteerde in respectievelijk 8, 37 en 61% TGI. Bij muizen met SKOV3 ovariumtumorxenografts resulteerde behandeling met 10, 30 en 100 mg/kg van deze verbinding in respectievelijk 23, 37 en 97% TGI.
Referenties	[1] https://pubmed.ncbi.nlm.nih.gov/24978597/

Toepassingen

Methoden	Biomarkers	Afbeeldingen	PMID
Western blot	p-GSK3 / GSK3 / p-PRAS40 / PRAS40 / p-FOXO / p-Casp9 / p-AKT / AKT / p-MEK / p-ERK / Erk ATG3 / ATG12 / LC3B		24978597

Informatie over klinische proeven

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

NCT-nummer	Werving	Aandoeningen	Sponsor/medewerkers	Startdatum	Fasen
NCT05489744	Completed	Healthy Volunteer	Laekna Limited	August 6 2022	Phase 1
NCT05390710	Completed	Solid Tumor\|TNBC - Triple-Negative Breast Cancer	Laekna Limited	June 12 2021	Phase 1
NCT04374630	Active not recruiting	Platinum-resistant Ovarian Cancer	Laekna Limited	June 9 2020	Phase 2
NCT04060394	Active not recruiting	Metastatic Castration-resistant Prostate Cancer	Laekna Limited	September 13 2019	Phase 1\|Phase 2
NCT02235740	Terminated	Cancer	Novartis\|Amgen	November 2014	Phase 1

Technische ondersteuning

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

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