Name: Ipatasertib (GDC-0068)
Brand: Selleck Chemicals
SKU: S2808
Rating: 5 (131 reviews)

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Controllo Qualità (Quality Control)

Lotto: Purezza: 99.87%

99.87

Target correlati	PI3K mTOR GSK-3 ATM/ATR DNA-PK AMPK PDPK1 PTEN PP2A PDK
Altro Akt Inibitori	SC79 AZD5363 (Capivasertib) MK-2206 Dihydrochloride Perifosine GSK690693 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	Concentrazione	Tempo di incubazione	Formulazione	Descrizione dell'attività	PMID
HCC70	Function Assay	1 μM	24 h		increases the abundance of HER3 and induces the phosphorylation (activation) of both EGFR and HER3	24667376
MDA-MB-468	Function Assay	1 μM	24 h		increases the abundance of HER3	24667376
HCC70	Growth Inhibition Assay	1 μM	5 d		enhances the antiproliferative response	24667376
MDA-MB-468	Growth Inhibition Assay	1 μM	5 d		enhances the antiproliferative response	24667376
PC-3	Function Assay	0.0038-2.5 μM	1 h	DMSO	induces a dose-dependent increase in Akt phosphorylation at both Thr308 (T308) and Ser473	23287563
BT474M1	Function Assay	0.0038-2.5 μM	1 h	DMSO	induces a dose-dependent increase in Akt phosphorylation at both Thr308 (T308) and Ser473	23287563
IGROV-1	Function Assay	0.0038-2.5 μM	1 h	DMSO	induces a dose-dependent increase in Akt phosphorylation at both Thr308 (T308) and Ser473	23287563
PC-3	Growth Inhibition Assay	1/5/10 μM	24/48/72 h	DMSO	dose-dependently increases the G0–G1 phase population	23287563
MCF7-neo/HER2	Growth Inhibition Assay	1/5/10 μM	24/48/72 h	DMSO	dose-dependently increases the G0–G1 phase population	23287563
BT474M1	Growth Inhibition Assay	1/5/10 μM	24/48/72 h	DMSO	dose-dependently increases the G0–G1 phase population	23287563
PC-3	Apoptosis Assay	1/5/10 μM	15/48/72 h	DMSO	causes a dose- and time-dependent increase in apoptotic and necrotic populations	23287563
MCF7-neo/HER2	Apoptosis Assay	1/5/10 μM	15/48/72 h	DMSO	causes a dose- and time-dependent increase in apoptotic and necrotic populations	23287563
BT474M1	Apoptosis Assay	1/5/10 μM	15/48/72 h	DMSO	causes a dose- and time-dependent increase in apoptotic and necrotic populations	23287563
LNCAP	Cytotoxicity assay		72 hrs		Cytotoxicity against human LNCAP cells assessed as reduction of resazurin to resorufin after 72 hrs, IC50 = 0.095 μM.	22934575
LNCAP	Function assay		1.5 hrs		Inhibition of Akt1 in human LNCAP cells assessed as phosphorylation of PRAS40 at Thr246 after 1.5 hrs, IC50 = 0.157 μM.	22934575
PC3	Function assay	50 mg/kg	9 hrs		Plasma concentration in nu/nu mouse xenografted with human PC3 cells at 50 mg/kg, po at 9 hrs by LC/MS/MS analysis, Cp = 0.5 μM.	22934575
BT474M1	Cytotoxicity assay		96 hrs		Cytotoxicity against human BT474M1 cells assessed as decrease in cell viability after 96 hrs by CellTitre-Glo assay, IC50 = 1 μM.	22934575
PC3	Cytotoxicity assay		96 hrs		Cytotoxicity against human PC3 cells assessed as decrease in cell viability after 96 hrs by CellTitre-Glo assay, IC50 = 1 μM.	22934575
MCF7	Cytotoxicity assay		96 hrs		Cytotoxicity against human MCF7 cells overexpressing Her2 assessed as decrease in cell viability after 96 hrs by CellTitre-Glo assay, IC50 = 1 μM.	22934575
PC3	Function assay	50 mg/kg	1 hr		Plasma concentration in nu/nu mouse xenografted with human PC3 cells at 50 mg/kg, po at 1 hr by LC/MS/MS analysis, Cp = 7.4 μM.	22934575
PC3	Function assay	100 mg/kg	8 hrs		Inhibition of Akt in nu/nu mouse xenografted with human PC3 cells assessed as decrease in tumor p-S6RP level at 100 mg/kg, po at 8 hrs by ELISA relative to total S6RP	22934575
MCF7	Function assay				Inhibition of Akt1-mediated PRAS40 phosphorylation in human MCF7 cells overexpressing Her2	22934575
BT474M1	Function assay				Inhibition of Akt1-mediated PRAS40 phosphorylation in human BT474M1 cells	22934575
PC3	Function assay				Inhibition of Akt1-mediated PRAS40 phosphorylation in human PC3 cells	22934575
LNCAP	Function assay				Inhibition of Akt1-mediated PRAS40 phosphorylation in human LNCAP cells	22934575
A673	qHTS assay				qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for A673 cells	29435139
DAOY	qHTS assay				qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for DAOY cells	29435139
Saos-2	qHTS assay				qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Saos-2 cells	29435139
BT-37	qHTS assay				qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for BT-37 cells	29435139
RD	qHTS assay				qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for RD 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
BT-12	qHTS assay				qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for BT-12 cells	29435139
MG 63 (6-TG R)	qHTS assay				qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for MG 63 (6-TG R) 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
LAN-5	qHTS assay				qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for LAN-5 cells	29435139
SK-N-SH	qHTS assay				qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for SK-N-SH cells	29435139
Rh41	qHTS assay				qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Rh41 cells	29435139
MG 63 (6-TG R)	qHTS assay				qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for MG 63 (6-TG R) cells	29435139
Rh30	qHTS assay				qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for Rh30 cells	29435139
Rh41	qHTS assay				qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for Rh41 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
Rh18	qHTS assay				qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Rh18 cells	29435139
SK-N-MC	qHTS assay				qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for SK-N-MC cells	29435139
TC32	qHTS assay				qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for TC32 cells	29435139
Saos-2	qHTS assay				qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for Saos-2 cells	29435139
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Informazioni chimiche, conservazione e stabilità (Chemical Information, Storage & Stability)

Peso molecolare	458	Formula	C₂₄H₃₂ClN₅O₂	Conservazione (Dalla data di ricezione)	3 anni-20°Cpolvere
N. CAS	1001264-89-6	Scarica SDF		Conservazione delle soluzioni stock	1 anno-80°Cin solvente 1 mese-20°Cin solvente
Sinonimi	RG7440			Smiles	CC1CC(C2=C1C(=NC=N2)N3CCN(CC3)C(=O)C(CNC(C)C)C4=CC=C(C=C4)Cl)O

Solubilità (Solubility)

In vitro
Lotto:

DMSO : 91 mg/mL (198.68 mM)
(Il DMSO contaminato da umidità può ridurre la solubilità. Utilizzare DMSO fresco e anidro.)

Ethanol : 91 mg/mL

Water : 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.
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.	4.600mg/ml (10.04mM)	Taking the 1 mL working solution as an example, add 50 μL of 92 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.
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	Akt1 (Cell-free assay) 5 nM Akt3 (Cell-free assay) 8 nM Akt2 (Cell-free assay) 18 nM
In vitro	Ipatasertib (GDC-0068) è stato testato contro un ampio pannello di 230 chinasi e inibisce solo 3 chinasi di >70% a una concentrazione di 1 μM (PRKG1α, PRKG1β e p70S6K, con IC50 di 98 nM, 69 nM e 860 nM, rispettivamente). Questo composto mostra una selettività >100 volte superiore per Akt rispetto a PKA con una IC50 di 3,1 μM. Nelle cellule LNCaP, PC3 e BT474M1, inibisce la fosforilazione del substrato di Akt, PRAS40, con IC50 di 157 nM, 197 nM e 208 nM, rispettivamente. Inoltre, inibisce selettivamente la progressione del ciclo cellulare e la vitalità delle linee cellulari tumorali guidate dalla segnalazione Akt, comprese quelle con difetti nel soppressore tumorale PTEN, mutazioni oncogeniche in PIK3CA e amplificazione di HER2, con gli effetti più forti nei sottotipi HER2⁺ e Luminal.
In vivo	La somministrazione orale di Ipatasertib (GDC-0068) nel modello di xenotrapianto di tumore prostatico PC3 induce la down-regolazione di p-PRAS40. Negli xenotrapianti BT474-Tr, questo composto riduce i livelli di pS6 e peIF4G, rilocalizza FOXO3a nel nucleo e induce l'up-regolazione di feedback di HER3 e pERK. Esibisce una potente efficacia antitumorale in diversi modelli di tumore xenotrapiantato, inclusi i modelli di cancro alla prostata deficienti di PTEN LNCaP e PC3, il modello di cancro al seno mutato PIK3CA H1047R KPL-4 e il modello di tumore MCF7-neo/HER2.
Riferimenti	[1] http://cancerres.aacrjournals.org/cgi/content/meeting_abstract/71/8_MeetingAbstracts/DDT02-01?sid=e2 [2] http://www.arraybiopharma.com/_documents/Publication/PubAttachment478.pdf [3] http://www.arraybiopharma.com/_documents/Publication/PubAttachment437.pdf [4] http://cancerres.aacrjournals.org/cgi/content/short/72/8_MeetingAbstracts/966?rss=1 [5] http://www.arraybiopharma.com/_documents/Publication/PubAttachment524.pdf [6] https://pubmed.ncbi.nlm.nih.gov/23287563/

Applicazioni (Applications)

Metodi	Biomarcatori	Immagini	PMID
Western blot	PUMA p-AKT / AKT / p-FoxO3a / FoxO3a / p-p65 / p65 Noxa / Bid / Bad / Bim / Bcl-2 / Bcl-xl / Mcl-1 cleaved-caspase3 p-PRAS40(T246) / PRAS40 / p-ERK / ERK / pFOXO1 / pFOXO3a / pGSK3b(S9) / pAS160(S318) / pBAD(S136) / pS6 / p4E-BP1		30185800

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
NCT01090960	Completed	Solid Cancers	Genentech Inc.	March 2010	Phase 1

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):

Ipatasertib (GDC-0068) Akt Inibitore

Struttura chimica

Peso molecolare: 458

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)

Ipatasertib (GDC-0068) Akt Inibitore

Struttura chimica

Peso molecolare: 458

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)

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