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

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Control de calidad

Lote: Pureza: 99.87%

99.87

Dianas relacionadas	PI3K mTOR GSK-3 ATM/ATR DNA-PK AMPK PDPK1 PTEN PP2A PDK
Otros Akt Inhibidores	SC79 AZD5363 (Capivasertib) MK-2206 Dihydrochloride Perifosine GSK690693 Triciribine (API-2) Afuresertib (GSK2110183) CCT128930 A-674563 HCl Akti-1/2

Cultivo celular, tratamiento y concentración de trabajo

Líneas celulares	Tipo de ensayo	Concentración	Tiempo de incubación	Formulación	Descripción de la actividad	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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Información química, almacenamiento y estabilidad

Peso molecular	458	Fórmula	C₂₄H₃₂ClN₅O₂	Almacenamiento (Desde la fecha de recepción)	3 años-20°Cpolvo
Nº CAS	1001264-89-6	Descargar SDF		Almacenamiento de soluciones madre	1 año-80°Cen disolvente 1 mes-20°Cen disolvente
Sinónimos	RG7440			Smiles	CC1CC(C2=C1C(=NC=N2)N3CCN(CC3)C(=O)C(CNC(C)C)C4=CC=C(C=C4)Cl)O

Solubilidad

In vitro
Lote:

DMSO : 91 mg/mL (198.68 mM)
(El DMSO contaminado con humedad puede reducir la solubilidad. Usar DMSO fresco y anhidro.)

Ethanol : 91 mg/mL

Water : Insoluble

Calculadora de Molaridad

Masa	Concentración	Volumen	Peso molecular
=	×	×

Calculadora de Dilución Calculadora de Peso Molecular

In vivo Lote:
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 Validado por los laboratorios Selleck. Si necesita ajustes en esta formulación, contacte con nuestro equipo de ventas para pruebas personalizadas.	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.

Calculadora de formulación in vivo (Solución clara)

Paso 1: Introduzca la información a continuación (Recomendado: Un animal adicional para tener en cuenta la pérdida durante el experimento)

Dosis: mg/kg Peso promedio de los animales: g Volumen de dosificación por animal:μL Número de animales:

Paso 2: Introduzca la formulación in vivo (Esto es solo la calculadora, no la formulación. Por favor, contáctenos primero si no hay una formulación in vivo en la sección de Solubilidad.)

% DMSO + % + % Tween 80 + % ddH₂O

%DMSO+ %

Resultados del cálculo:

Concentración de trabajo: mg/ml;

Método para preparar el líquido maestro de DMSO: mg fármaco predissuelto en μL DMSO ( Concentración del líquido maestro mg/mL, Por favor, contáctenos primero si la concentración excede la solubilidad del DMSO del lote del fármaco. )

Método para preparar la formulación in vivo: Tomar μL DMSO líquido maestro, luego añadirμL PEG300, mezclar y clarificar, luego añadirμL Tween 80, mezclar y clarificar, luego añadir μL ddH₂O, mezclar y clarificar.

Método para preparar la formulación in vivo: Tomar μL DMSO líquido maestro, luego añadir μL Aceite de maíz, mezclar y clarificar.

Nota: 1. Por favor, asegúrese de que el líquido esté claro antes de añadir el siguiente disolvente.
2. Asegúrese de añadir el (los) disolvente(s) en orden. Debe asegurarse de que la solución obtenida, en la adición anterior, sea una solución clara antes de proceder a añadir el siguiente disolvente. Se pueden utilizar métodos físicos como el vórtice, el ultrasonido o el baño de agua caliente para ayudar a la disolución.

Mecanismo de acción

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) se probó contra un amplio panel de 230 quinasas, e inhibe solo 3 quinasas en >70% a una concentración de 1 μM (PRKG1α, PRKG1β y p70S6K, con IC50 de 98 nM, 69 nM y 860 nM, respectivamente). Este compuesto muestra una selectividad >100 veces mayor para Akt sobre PKA con una IC50 de 3,1 μM. En células LNCaP, PC3 y BT474M1, inhibe la fosforilación del sustrato de Akt, PRAS40, con una IC50 de 157 nM, 197 nM y 208 nM, respectivamente. Además, inhibe selectivamente la progresión del ciclo celular y la viabilidad de las líneas celulares cancerosas impulsadas por la señalización de Akt, incluidas aquellas con defectos en el supresor tumoral PTEN, mutaciones oncogénicas en PIK3CA y amplificación de HER2, con los efectos más fuertes en los subtipos HER2⁺ y Luminal.
In vivo	La administración oral de Ipatasertib (GDC-0068) en el modelo de xenoinjertos de tumores de próstata PC3 induce la regulación a la baja de p-PRAS40. En los xenoinjertos BT474-Tr, este compuesto reduce los niveles de pS6 y peIF4G, reubica FOXO3a al núcleo e induce la regulación al alza por retroalimentación de HER3 y pERK. Exhibe una potente eficacia antitumoral en múltiples modelos de tumores xenoinjertados, incluidos los modelos de cáncer de próstata deficientes en PTEN LNCaP y PC3, el modelo de cáncer de mama mutante PIK3CA H1047R KPL-4 y el modelo de tumor MCF7-neo/HER2.
Referencias	[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/

Aplicaciones

Métodos	Biomarcadores	Imágenes	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

Información del ensayo clínico

(datos de https://clinicaltrials.gov, actualizado el 2024-05-22)

Número NCT	Reclutamiento	Condiciones	Patrocinador/Colaboradores	Fecha de inicio	Fases
NCT01090960	Completed	Solid Cancers	Genentech Inc.	March 2010	Phase 1

Soporte técnico

Instrucciones de manipulación

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

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Ipatasertib (GDC-0068) Akt inhibidor

Estructura química

Peso molecular: 458