Name: GSK690693
Brand: Selleck Chemicals
SKU: S1113
Rating: 5 (126 reviews)

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Controllo Qualità (Quality Control)

Lotto: Purezza: 99.09%

99.09

Target correlati	PI3K mTOR GSK-3 ATM/ATR DNA-PK AMPK PDPK1 PTEN PP2A PDK
Altro Akt Inibitori	SC79 AZD5363 (Capivasertib) MK-2206 Dihydrochloride Ipatasertib (GDC-0068) Perifosine Triciribine (API-2) Afuresertib (GSK2110183) CCT128930 A-674563 HCl AKTi-1/2 (AKT Inhibitor VIII)

Coltura cellulare, trattamento e concentrazione di lavoro
(Cell Culture, Treatment & Working Concentration)

Linee cellulari	Tipo di saggio	Tempo di incubazione	Descrizione dell'attività	PMID
LNCaP	Proliferation assay		Antiproliferative activity against human LNCaP cells, IC50=20 nM	18800763
BT474	Proliferation assay		Antiproliferative activity against human BT474 cells, IC50=50 nM	18800763
Sf9	Function assay		Inhibition of human recombinant ROCK1 expressed in Sf9 cells, IC50=0.89 μM	18800763
NCI-H460	Growth inhibition assay	72 h	Growth inhibition of human NCI-H460 cells after 72 hrs by coulter counter method, IC50=5.4 μM	24900862
PC3	Proliferation assay	72 h	Antiproliferative activity against human PC3 cells after 72 hrs by MTT assay, IC50=15.5 μM	24308997
HFF	Cytotoxic assay		Cytotoxicity against HFF cells, IC50=16.3 μM	18800763
LNCAP	Antiproliferative assay		Antiproliferative activity against human LNCAP cells, IC50 = 0.021 μM.	19179070
BT474	Antiproliferative assay		Antiproliferative activity against human BT474 cells, IC50 = 0.069 μM.	19179070
BT474	Function assay		Inhibition of GSK3-beta phosphorylation in human BT474 cells, IC50 = 0.138 μM.	19179070
JVM2	Antiproliferative assay	72 hrs	Antiproliferative activity against human JVM2 cells after 72 hrs by CellTiter Glo assay, IC50 = 1.6 μM.	28704757
JeKo1	Antiproliferative assay	72 hrs	Antiproliferative activity against human JeKo1 cells after 72 hrs by CellTiter Glo assay, IC50 = 3 μM.	28704757
Z138	Antiproliferative assay	72 hrs	Antiproliferative activity against human Z138 cells after 72 hrs by CellTiter Glo assay, IC50 = 3.1 μM.	28704757
SP49	Antiproliferative assay	72 hrs	Antiproliferative activity against human SP49 cells after 72 hrs by CellTiter Glo assay, IC50 = 4.8 μM.	28704757
Maver1	Antiproliferative assay	72 hrs	Antiproliferative activity against human Maver1 cells after 72 hrs by CellTiter Glo assay, IC50 = 5.1 μM.	28704757
C6	Function assay	24 hrs	Inhibition of Akt in rat C6 cells after 24 hrs by ELISA, IC50 = 6.97 μM.	29966916
C6	Cytotoxicity assay	24 hrs	Cytotoxicity against rat C6 cells assessed as decrease in cell viability after 24 hrs by MTT assay, IC50 = 14.5 μM.	29966916
A549	Function assay	24 hrs	Inhibition of Akt in human A549 cells after 24 hrs by ELISA, IC50 = 17.33 μM.	29966916
Mino	Antiproliferative assay	72 hrs	Antiproliferative activity against human Mino cells after 72 hrs by CellTiter Glo assay, IC50 = 20.8 μM.	28704757
A673	qHTS assay		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for A673 cells	29435139
RD	qHTS assay		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for RD cells	29435139
NB1643	qHTS assay		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for NB1643 cells	29435139
SJ-GBM2	qHTS assay		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for SJ-GBM2 cells	29435139
SK-N-MC	qHTS assay		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for SK-N-MC cells	29435139
NB-EBc1	qHTS assay		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for NB-EBc1 cells	29435139
LAN-5	qHTS assay		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for LAN-5 cells	29435139
MCL	Antiproliferative assay	24 hrs	Antiproliferative activity against primary human MCL cells up to 60 uM after 24 hrs by CellTiter Glo assay	28704757
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Informazioni chimiche, conservazione e stabilità (Chemical Information, Storage & Stability)

Peso molecolare	425.48	Formula	C₂₁H₂₇N₇O₃	Conservazione (Dalla data di ricezione)	3 anni-20°Cpolvere
N. CAS	937174-76-0	Scarica SDF		Conservazione delle soluzioni stock	1 anno-80°Cin solvente 1 mese-20°Cin solvente
Sinonimi	N/A			Smiles	CCN1C2=C(C(=NC=C2OCC3CCCNC3)C#CC(C)(C)O)N=C1C4=NON=C4N

Solubilità (Solubility)

In vitro
Lotto:

DMSO : 21 mg/mL (49.35 mM)
(Il DMSO contaminato da umidità può ridurre la solubilità. Utilizzare DMSO fresco e anidro.)

Water : Insoluble

Ethanol : Insoluble

Calcolatore di Molarità

Massa	Concentrazione	Volume	Peso molecolare
=	×	×

Calcolatore di Diluizione Calcolatore del Peso Molecolare

In vivo Lotto:
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 Validato dai laboratori Selleck. Se necessiti di modifiche a questa formulazione, contatta il nostro team di vendita per test personalizzati.	3.000mg/ml (7.05mM)	Taking the 1 mL working solution as an example, add 50 μL of 60 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.
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.
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.

Calcolatore di formulazione in vivo (Soluzione chiara)

Passo 1: Inserire le informazioni di seguito (Consigliato: Un animale aggiuntivo per tenere conto della perdita durante l'esperimento)

Dosaggio: mg/kg Peso medio degli animali: g Volume di dosaggio per animale:μL Numero di animali:

Passo 2: Inserire la formulazione in vivo (Questo è solo il calcolatore, non la formulazione. Contattateci prima se non c'è una formulazione in vivo nella sezione Solubilità.)

% DMSO + % + % Tween 80 + % ddH₂O

%DMSO+ %

Risultati del calcolo:

Concentrazione di lavoro: mg/ml;

Metodo per preparare il liquido master di DMSO: mg farmaco predissolto in μL DMSO ( Concentrazione del liquido master mg/mL, Vi preghiamo di contattarci prima se la concentrazione supera la solubilità del DMSO del lotto del farmaco. )

Metodo per preparare la formulazione in vivo: Prendere μL DMSO liquido master, quindi aggiungereμL PEG300, mescolare e chiarire, quindi aggiungereμL Tween 80, mescolare e chiarire, quindi aggiungere μL ddH₂O, mescolare e chiarire.

Metodo per preparare la formulazione in vivo: Prendere μL DMSO liquido master, quindi aggiungere μL Olio di mais, mescolare e chiarire.

Nota: 1. Si prega di assicurarsi che il liquido sia limpido prima di aggiungere il solvente successivo.
2. Assicurarsi di aggiungere il/i solvente/i in ordine. È necessario assicurarsi che la soluzione ottenuta, nell'aggiunta precedente, sia una soluzione limpida prima di procedere all'aggiunta del solvente successivo. Metodi fisici come il vortex, gli ultrasuoni o il bagno d'acqua calda possono essere utilizzati per facilitare la dissoluzione.

Meccanismo d'azione (Mechanism of Action)

Targets/IC₅₀/Ki	ULK1 STING AMPK Akt1 (Cell-free assay) 2 nM PKCη (Cell-free assay) 2 nM PKCθ (Cell-free assay) 2 nM PrkX (Cell-free assay) 5 nM Akt3 (Cell-free assay) 9 nM Akt2 (Cell-free assay) 13 nM PKCδ (Cell-free assay) 14 nM PKCβ (Cell-free assay) 19 nM PKCε (Cell-free assay) 21 nM PKA (Cell-free assay) 24 nM PKG1β (Cell-free assay) 33 nM
In vitro	GSK690693 is very selective for the Akt isoforms versus the majority of kinases in other families. However, this compound is less selective for members of the AGC kinase family including PKA, PrkX, and PKC isozymes with IC50 of 24 nM, 5 nM, and 2-21 nM, respectively. It also potently inhibits AMPK and DAPK3 from the CAMK family with IC50 of 50 nM and 81 nM, respectively, and PAK4, 5, and 6 from the STE family with IC50 of 10 nM, 52 nM, and 6 nM, respectively. This chemical inhibits the phosphorylation of GSK3β in tumor cells with IC50 ranging from 43 nM to 150 nM. Its treatment leads to a dose-dependent increase in the nuclear accumulation of the transcription factor FOXO3A. This compound potently inhibits the proliferation of T47D, ZR-75-1, BT474, HCC1954, MDA-MB-453, and LNCaP cells with IC50 of 72 nM, 79 nM, 86 nM, 119 nM, 975 nM, and 147 nM, respectively. Its treatment induces apoptosis at concentrations >100 nM in both LNCaP and BT474 cells. Consistent with the role of AKT in cell survival, it induces apoptosis in sensitive ALL cell lines.
Saggio chinasico	Saggi chinasici in vitro
Saggio chinasico	Akt1, 2 o 3 a lunghezza intera con tag His vengono espressi e purificati da baculovirus. L'attivazione viene eseguita con PDK1 purificata per fosforilare Thr308 e MK2 purificata per fosforilare Ser473. Per misurare con maggiore precisione l'inibizione tempo-dipendente di Akt, gli enzimi Akt attivati vengono incubati con GSK690693 a varie concentrazioni a temperatura ambiente per 30 minuti prima che la reazione venga avviata con l'aggiunta di substrato. La reazione finale contiene da 5 nM a 15 nM di enzimi Akt1, 2 e 3; 2 μM di ATP; 0,15 μCi/μL [γ-³³P]ATP; 1 μM di peptide (Biotin-aminohexanoicacid-ARKR-ERAYSFGHHA-amide); 10 mM di MgCl₂; 25 mM di MOPS (pH 7,5); 1 mM di DTT; 1 mM di CHAPS; e 50 mM di KCl. Le reazioni vengono incubate a temperatura ambiente per 45 minuti, seguite dall'interruzione con perle Leadseeker in PBS contenente EDTA (concentrazione finale, 2 mg/mL di perle e 75 mM di EDTA). Le piastre vengono quindi sigillate, le perle vengono lasciate sedimentare per almeno 5 ore e la formazione del prodotto viene quantificata utilizzando un Viewlux Imager.
In vivo	A single administration of GSK690693 inhibits GSK3β phosphorylation in human breast carcinoma (BT474) xenografts in a dose- and time-dependent manner. Similarly, this compound induces a reduction in phosphorylation of the Akt substrates, PRAS40, and FKHR/FKHRL1. It also results in an acute increase in blood glucose, returning to baseline 8 to 10 hours after drug administration. Administration of this chemical induces reductions in phosphorylated Akt substrates in vivo, and potently inhibits the growth of human SKOV-3 ovarian, LNCaP prostate, and BT474 and HCC-1954 breast carcinoma xenografts, with maximal inhibition of 58% to 75% at the dose of 30 mg/kg/day. This compound exhibits efficacy irrespective of the mechanism of Akt activation involved. It is most effective in delaying tumor progression in Lck-MyrAkt2 mice expressing a membrane-bound, constitutively active form of Akt.
Riferimenti	[1] https://pubmed.ncbi.nlm.nih.gov/18381444/ [2] https://pubmed.ncbi.nlm.nih.gov/19064730/ [3] https://pubmed.ncbi.nlm.nih.gov/20075391/ [4] https://pubmed.ncbi.nlm.nih.gov/29694889/

Applicazioni (Applications)

Metodi	Biomarcatori	Immagini	PMID
Western blot	p-Akt / Akt / p-GSK3 / p-mTOR / mTOR / p-p70S6K / p-FoxO3a / p-FoxO1 pPRAS40 / PRAS40 / pBAD / BAD		20075391
Growth inhibition assay	Cell viability		20075391

Informazioni sullo studio clinico (Clinical Trial Information)

(dati da https://clinicaltrials.gov, aggiornato il 2024-05-22)

Numero NCT	Reclutamento	Condizioni	Sponsor/Collaboratori	Data di inizio	Fasi
NCT00666081	Withdrawn	Cancer	GlaxoSmithKline	April 2008	Phase 1
NCT00493818	Terminated	Cancer	GlaxoSmithKline	April 2007	Phase 1

Domande Frequenti (Frequently Asked Questions)

Domanda 1:
Why did pAKT increase after treatment with it?

Risposta:
It actually inhibits AKT, but does not necessarily decrease p-Akt level. Treatment with this compound caused AKT hyper phosphorylation which has already been reported in some papers. (For example, http://www.bloodjournal.org/content/113/8/1723.short?sso-checked=true). To test the inhibition of AKT activity, you might have to look at the level of AKT substrates.

C1=C0/X	C1:	LOG(C1):
C2=C1/X	C2:	LOG(C2):
C3=C2/X	C3:	LOG(C3):
C4=C3/X	C4:	LOG(C4):
C5=C4/X	C5:	LOG(C5):
C6=C5/X	C6:	LOG(C6):
C7=C6/X	C7:	LOG(C7):
C8=C7/X	C8:	LOG(C8):

GSK690693 pan-Akt Inhibitor

Struttura chimica

Peso molecolare: 425.48

Controllo Qualità (Quality Control)

Coltura cellulare, trattamento e concentrazione di lavoro
(Cell Culture, Treatment & Working Concentration)

Informazioni chimiche, conservazione e stabilità (Chemical Information, Storage & Stability)

Solubilità (Solubility)

Calcolatore di Molarità

Calcolatore di formulazione in vivo (Soluzione chiara)

Meccanismo d'azione (Mechanism of Action)

Applicazioni (Applications)

Informazioni sullo studio clinico (Clinical Trial Information)

Domande Frequenti (Frequently Asked Questions)

GSK690693 pan-Akt Inhibitor

Struttura chimica

Peso molecolare: 425.48

Controllo Qualità (Quality Control)

Coltura cellulare, trattamento e concentrazione di lavoro (Cell Culture, Treatment & Working Concentration)

Informazioni chimiche, conservazione e stabilità (Chemical Information, Storage & Stability)

Solubilità (Solubility)

Calcolatore di Molarità

Calcolatore di formulazione in vivo (Soluzione chiara)

Meccanismo d'azione (Mechanism of Action)

Applicazioni (Applications)

Informazioni sullo studio clinico (Clinical Trial Information)

Domande Frequenti (Frequently Asked Questions)

Coltura cellulare, trattamento e concentrazione di lavoro
(Cell Culture, Treatment & Working Concentration)