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Afuresertib (GSK2110183) Akt Inhibitor

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

Kat.-Nr.S7521

Afuresertib (GSK2110183) ist ein potenter, oral bioverfügbarer Akt-Inhibitor mit K_i-Werten von 0,08 nM, 2 nM und 2,6 nM für Akt1, Akt2 bzw. Akt3 und befindet sich derzeit in Phase-2-Studien.

Afuresertib (GSK2110183) Akt Inhibitor Chemical Structure

Chemische Struktur

Molekulargewicht: 427.32

Springe zu

Qualitätskontrolle

Charge: Reinheit: 99.61%

99.61

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

Zellkultur, Behandlung & Arbeitskonzentration

Zelllinien	Assay-Typ	Inkubationszeit	Aktivitätsbeschreibung	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 Informationen, Lagerung & Stabilität

Molekulargewicht	427.32	Formel	C₁₈H₁₇Cl₂FN₄OS	Lagerung (Ab dem Eingangsdatum)	3 Jahre-20°CPulver
CAS-Nr.	1047644-62-1	SDF herunterladen		Lagerung von Stammlösungen	1 Jahr-80°Cin Lösungsmittel 1 Monat-20°Cin Lösungsmittel
Synonyme	N/A			Smiles	CN1C(=C(C=N1)Cl)C2=C(SC(=C2)C(=O)NC(CC3=CC(=CC=C3)F)CN)Cl

Löslichkeit

In vitro
Charge:

DMSO : 85 mg/mL (198.91 mM)
(Feuchtigkeitskontaminiertes DMSO kann die Löslichkeit verringern. Verwenden Sie frisches, wasserfreies DMSO.)

Ethanol : 85 mg/mL

Water : Insoluble

DMSO : 85 mg/mL (198.91 mM)
(Feuchtigkeitskontaminiertes DMSO kann die Löslichkeit verringern. Verwenden Sie frisches, wasserfreies DMSO.)

Ethanol : 85 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.

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

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) hemmt die Kinaseaktivität des E17K AKT1-Mutationsproteins mit einer EC50 von 0,2 nM. Es zeigt einen konzentrationsabhängigen Effekt auf multiple AKT-Substratphosphorylierungslevel, einschließlich GSK3b, PRAS40, FOXO und Caspase 9. Insgesamt sind 65 % der hämatologischen Zelllinien empfindlich gegenüber dieser Verbindung (EC50 < 1 μM). Unter den getesteten soliden Tumorzelllinien weisen 21 % eine EC50 < 1 μM als Reaktion auf Afuresertib auf.
Kinase-Assay	Potenz (Ki*) von Afuresertib
Kinase-Assay	Die wahre Potenz (Ki*) von Afuresertib (GSK2110183) wird zunächst bei niedrigen Enzymkonzentrationen (0,1 nM AKT1, 0,7 nM AKT2 und 0,2 nM AKT3) mittels eines Filterbindungsassays bestimmt und anschließend durch Progressionskurvenanalyse bestätigt. Im Filterbindungsassay wird eine Vormischung aus Enzym plus dieser Verbindung 1 Stunde lang inkubiert und dann zu einem GSKα-Peptid (Ac-KKGGRARTSS-FAEPG-amid) und [γ³³P] ATP gegeben. Die Reaktionen werden nach 2 Stunden beendet und das radiomarkierte AKT-Peptidprodukt wird in einer Phospho-Cellulose-Filterplatte eingefangen. Die Progressionskurvenanalyse verwendet die kontinuierliche Echtzeit-Fluoreszenzdetektion der Produktbildung unter Verwendung des Sox-AKT-tide-Substrats (Ac-ARKRERAYSF-d-Pro-Sox-Gly-NH2).
In vivo	Afuresertib (GSK2110183) wurde Mäusen mit BT474-Brusttumor-Xenografts oral in Dosen von 10, 30 oder 100 mg/kg täglich verabreicht, was zu einer TGI von 8, 37 bzw. 61 % führte. Bei Mäusen mit SKOV3-Ovarialtumor-Xenografts führte die Behandlung mit 10, 30 und 100 mg/kg dieser Verbindung zu einer TGI von 23, 37 bzw. 97 %.
Literatur	[1] https://pubmed.ncbi.nlm.nih.gov/24978597/

Anwendungen

Methoden	Biomarker	Bilder	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

Klinische Studieninformationen

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

NCT-Nummer	Rekrutierung	Erkrankungen	Sponsor/Kooperationspartner	Startdatum	Phasen
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

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