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

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Kvalitetskontroll (Quality Control)

Batch: Renhet: 99.87%

99.87

Relaterade mål	PI3K mTOR GSK-3 ATM/ATR DNA-PK AMPK PDPK1 PTEN PP2A PDK
Övrigt Akt Inhibitorer	SC79 AZD5363 (Capivasertib) MK-2206 Dihydrochloride Perifosine GSK690693 Triciribine (API-2) Afuresertib (GSK2110183) CCT128930 A-674563 HCl AKTi-1/2 (AKT Inhibitor VIII)

Cellodling, behandling & arbetskoncentration
(Cell Culture, Treatment & Working Concentration)

Cellinjer	Analystyp	Koncentration	Inkubationstid	Formulering	Aktivitetsbeskrivning	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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Kemisk information, lagring & stabilitet (Chemical Information, Storage & Stability)

Molekylvikt	458	Formel	C₂₄H₃₂ClN₅O₂	Lagring (från mottagningsdatumet)	3 år-20°Cpulver
CAS-nr	1001264-89-6	Ladda ner SDF		Lagring av stamlösningar	1 år-80°Ci lösningsmedel 1 månad-20°Ci lösningsmedel
Synonymer	RG7440			Smiles	CC1CC(C2=C1C(=NC=N2)N3CCN(CC3)C(=O)C(CNC(C)C)C4=CC=C(C=C4)Cl)O

Löslighet (Solubility)

In vitro
Batch:

DMSO : 91 mg/mL (198.68 mM)
(Fuktkontaminerad DMSO kan minska lösligheten. Använd färk, vattenfri DMSO.)

Ethanol : 91 mg/mL

Water : Insoluble

Molaritetsräknare

Massa	Koncentration	Volym	Molekylvikt
=	×	×

Utspädningsräknare Molekylviktsräknare

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.
Clear solution	5%DMSO 1 40%PEG300 2 5%Tween80 3 50%ddH2O Validerad av Selleck-laboratorier. Om du behöver justeringar av denna formulering, kontakta vårt säljteam för skräddarsydd testning.	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.

In vivo-formuleringsräknare (Klar lösning)

Steg 1: Ange information nedan (Rekommenderas: Ett extra djur för att ta hänsyn till förluster under experimentet)

Dosering: mg/kg Djurens medelvikt: g Doseringsvolym per djur:μL Antal djur:

Steg 2: Ange in vivo-formuleringen (Detta är endast räknaren, inte formuleringen. Vänligen kontakta oss först om det inte finns någon in vivo-formulering i löslighetsavsnittet.)

% DMSO + % + % Tween 80 + % ddH₂O

%DMSO+ %

Beräkningsresultat:

Arbetskoncentration: mg/ml;

Metod för att bereda DMSO-stamlösning: mg substans förlöst i μL DMSO ( Stamlösningskoncentration mg/mL, Vänligen kontakta oss först om koncentrationen överskrider DMSO-lösligheten för denna batch av substansen. )

Metod för att bereda in vivo-formulering: Ta μL DMSO stamlösning, tillsätt sedanμL PEG300, blanda och klarna, tillsätt sedanμL Tween 80, blanda och klarna, tillsätt sedan μL ddH₂O, blanda och klarna.

Metod för att bereda in vivo-formulering: Ta μL DMSO stamlösning, tillsätt sedan μL Majsolja, blanda och klarna.

Obs: 1. Se till att vätskan är klar innan du tillsätter nästa lösningsmedel.
2. Se till att tillsätta lösningsmedlet/lösningsmedlen i ordning. Du måste se till att lösningen som erhålls i föregående tillsats är en klar lösning innan du fortsätter att tillsätta nästa lösningsmedel. Fysiska metoder som vortex, ultraljud eller varmt vattenbad kan användas för att underlätta upplösningen.

Verkningsmekanism (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) was tested against a broad panel of 230 kinases, and it only inhibits 3 kinases by >70% at 1 μM concentration (PRKG1α, PRKG1β, and p70S6K, with IC50 of 98 nM, 69 nM, and 860 nM, respectively). This compound displays >100-fold selectivity for Akt over PKA with IC50 of 3.1 μM. In LNCaP, PC3 and BT474M1 cells, it inhibits the phosphorylation of the Akt substrate, PRAS40 with IC50 of 157 nM, 197 nM, and 208 nM, respectively. Furthermore, it selectively inhibits cell cycle progression and viability of cancer cell lines driven by Akt signaling, including those with defects in the tumor suppressor PTEN, oncogenic mutations in PIK3CA, and amplification of HER2, with strongest effects in HER2⁺ and Luminal subtypes.
In vivo	Oral administration of Ipatasertib (GDC-0068) in PC3 prostate tumor xenografts model induces down-regulation of p-PRAS40. In BT474-Tr xenografts, this compound reduces pS6 and peIF4G levels, re-localizes FOXO3a to nucleus, and induces feedback upregulation of HER3 and pERK. It exhibits potent antitumor efficacy in multiple xenograft tumor models, including the PTEN-deficient prostate cancer models LNCaP and PC3, the PIK3CA H1047R mutant breast cancer model KPL-4, and MCF7-neo/HER2 tumor model.
Referenser	[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/

Applikationer (Applications)

Metoder	Biomarkörer	Bilder	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

Klinisk prövningsinformation (Clinical Trial Information)

(data från https://clinicaltrials.gov, uppdaterad den 2024-05-22)

NCT-nummer	Rekrytering	Tillstånd	Sponsor/Samarbetspartners	Startdatum	Faser
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 Hämmare

Molekylvikt: 458

Kvalitetskontroll (Quality Control)

Cellodling, behandling & arbetskoncentration
(Cell Culture, Treatment & Working Concentration)

Kemisk information, lagring & stabilitet (Chemical Information, Storage & Stability)

Löslighet (Solubility)

Molaritetsräknare

In vivo-formuleringsräknare (Klar lösning)

Verkningsmekanism (Mechanism of Action)

Applikationer (Applications)

Klinisk prövningsinformation (Clinical Trial Information)

Ipatasertib (GDC-0068) Akt Hämmare

Molekylvikt: 458

Kvalitetskontroll (Quality Control)

Cellodling, behandling & arbetskoncentration (Cell Culture, Treatment & Working Concentration)

Kemisk information, lagring & stabilitet (Chemical Information, Storage & Stability)

Löslighet (Solubility)

Molaritetsräknare

In vivo-formuleringsräknare (Klar lösning)

Verkningsmekanism (Mechanism of Action)

Applikationer (Applications)

Klinisk prövningsinformation (Clinical Trial Information)

Cellodling, behandling & arbetskoncentration
(Cell Culture, Treatment & Working Concentration)