Reagenti e strumenti per immunologia, biologia cellulare e biologia molecolare

Ipatasertib [1001264-89-6]

Stampa

Cat# HY-15186-100mg

Size : 100mg

Marca : MedChemExpress

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Description

Ipatasertib (GDC-0068) is an orally active, highly selective and ATP-competitive pan-Akt inhibitor with IC₅₀ values of 5, 18, 8 nM for Akt1/2/3, respectively. Ipatasertib synchronously activates FoxO3a and NF-κB through inhibition of Akt leading to p53-independent activation of PUMA. Ipatasertib also induces apoptosis in cancer cells and inhibits tumor growth in xenograft mouse models^[1]^[2].

IC₅₀ & Target^[2]

Akt1

5 nM (IC₅₀)

Akt3

8 nM (IC₅₀)

Akt2

18 nM (IC₅₀)

PKA

3100 nM (IC₅₀)

Cellular Effect

Cell Line	Type	Value	Description	References
AN3-CA	EC₅₀	925 nM Compound: Ipatasertib	Antiproliferative activity against human AN3-CA cells assessed as reduction in cell viability incubated for 5 days by celltiter-glo assay Antiproliferative activity against human AN3-CA cells assessed as reduction in cell viability incubated for 5 days by celltiter-glo assay	[PMID: 30996949]
BT-474	EC₅₀	2371 nM Compound: Ipatasertib	Antiproliferative activity against human BT-474 cells assessed as reduction in cell viability incubated for 5 days by celltiter-glo assay Antiproliferative activity against human BT-474 cells assessed as reduction in cell viability incubated for 5 days by celltiter-glo assay	[PMID: 30996949]
BT-474	GI₅₀	0.3 μM Compound: GDC-0068	Antiproliferative activity against human BT-474 cells assessed as growth inhibition incubated for 5 days by IncuCyte live-cell imaging analysis Antiproliferative activity against human BT-474 cells assessed as growth inhibition incubated for 5 days by IncuCyte live-cell imaging analysis	[PMID: 34855399]
C-33-A	IC₅₀	725.97 nM Compound: GDC-0068	Antiproliferative activity against human C-33-A habouring PTEN deletion mutant assessed as reduction in cell viability incubated for 72 hrs by Cell Titer Glo luminescent assay Antiproliferative activity against human C-33-A habouring PTEN deletion mutant assessed as reduction in cell viability incubated for 72 hrs by Cell Titer Glo luminescent assay	[PMID: 35679512]
CAL-51	IC₅₀	265.2 nM Compound: GDC-0068	Antiproliferative activity against human CAL-51 habouring PTEN deletion and PIK3CA mutation/amplication assessed as reduction in cell viability incubated for 72 hrs by Cell Titer Glo luminescent assay Antiproliferative activity against human CAL-51 habouring PTEN deletion and PIK3CA mutation/amplication assessed as reduction in cell viability incubated for 72 hrs by Cell Titer Glo luminescent assay	[PMID: 35679512]
Hep 3B2	IC₅₀	389 μM Compound: GDC-0068	Cytotoxicity against human Hep3B cells assessed as reduction in cell viability by MTT assay Cytotoxicity against human Hep3B cells assessed as reduction in cell viability by MTT assay	[PMID: 32007668]
HepG2	IC₅₀	0.268 μM Compound: GDC-0068	Cytotoxicity against human HepG2 cells assessed as reduction in cell viability by MTT assay Cytotoxicity against human HepG2 cells assessed as reduction in cell viability by MTT assay	[PMID: 32007668]
Huh-7	IC₅₀	0.167 μM Compound: GDC-0068	Cytotoxicity against human Huh-7 cells assessed as reduction in cell viability by MTT assay Cytotoxicity against human Huh-7 cells assessed as reduction in cell viability by MTT assay	[PMID: 32007668]
KU-19-19	EC₅₀	24037 nM Compound: Ipatasertib	Antiproliferative activity against human KU-19-19 cells assessed as reduction in cell viability incubated for 5 days by celltiter-glo assay Antiproliferative activity against human KU-19-19 cells assessed as reduction in cell viability incubated for 5 days by celltiter-glo assay	[PMID: 30996949]
LNCaP	IC₅₀	157 nM Compound: 28, GDC-0068	Inhibition of Akt1 in human LNCAP cells assessed as phosphorylation of PRAS40 at Thr246 after 1.5 hrs Inhibition of Akt1 in human LNCAP cells assessed as phosphorylation of PRAS40 at Thr246 after 1.5 hrs	[PMID: 22934575]
LNCaP	IC₅₀	95 nM Compound: 28, GDC-0068	Cytotoxicity against human LNCAP cells assessed as reduction of resazurin to resorufin after 72 hrs Cytotoxicity against human LNCAP cells assessed as reduction of resazurin to resorufin after 72 hrs	[PMID: 22934575]
MCF7	EC₅₀	5036 nM Compound: Ipatasertib	Antiproliferative activity against human MCF7 cells assessed as reduction in cell viability incubated for 5 days by celltiter-glo assay Antiproliferative activity against human MCF7 cells assessed as reduction in cell viability incubated for 5 days by celltiter-glo assay	[PMID: 30996949]
MCF7	IC₅₀	1 μM Compound: 28, GDC-0068	Cytotoxicity against human MCF7 cells overexpressing Her2 assessed as decrease in cell viability after 96 hrs by CellTitre-Glo assay Cytotoxicity against human MCF7 cells overexpressing Her2 assessed as decrease in cell viability after 96 hrs by CellTitre-Glo assay	[PMID: 22934575]
MDA-MB-468	GI₅₀	3.7 μM Compound: GDC-0068	Antiproliferative activity against human MDA-MB-468 cells assessed as growth inhibition incubated for 5 days by IncuCyte live-cell imaging analysis Antiproliferative activity against human MDA-MB-468 cells assessed as growth inhibition incubated for 5 days by IncuCyte live-cell imaging analysis	[PMID: 34855399]
NCI-H1975	IC₅₀	>20 μM Compound: 2; GDC-0068	Antiproliferative activity against human osimertinib resistant NCI-H1975 cells assessed as reduction in cell viability measured after 24 hrs by CCK-8 assay Antiproliferative activity against human osimertinib resistant NCI-H1975 cells assessed as reduction in cell viability measured after 24 hrs by CCK-8 assay	[PMID: 36173763]
PC-3	GI₅₀	7.6 μM Compound: GDC-0068	Antiproliferative activity against human PC-3 cells assessed as growth inhibition incubated for 5 days by IncuCyte live-cell imaging analysis Antiproliferative activity against human PC-3 cells assessed as growth inhibition incubated for 5 days by IncuCyte live-cell imaging analysis	[PMID: 34855399]
PC-3	IC₅₀	1 μM Compound: 28, GDC-0068	Cytotoxicity against human PC3 cells assessed as decrease in cell viability after 96 hrs by CellTitre-Glo assay Cytotoxicity against human PC3 cells assessed as decrease in cell viability after 96 hrs by CellTitre-Glo assay	[PMID: 22934575]
PC-3	IC₅₀	3544.33 nM Compound: GDC-0068	Antiproliferative activity against human PC-3 habouring PTEN deletion and PIK3CA mutation/amplication assessed as reduction in cell viability incubated for 72 hrs by Cell Titer Glo luminescent assay Antiproliferative activity against human PC-3 habouring PTEN deletion and PIK3CA mutation/amplication assessed as reduction in cell viability incubated for 72 hrs by Cell Titer Glo luminescent assay	[PMID: 35679512]
RL95-2	IC₅₀	331.07 nM Compound: GDC-0068	Antiproliferative activity against human RL95-2 habouring PTEN deletion mutant assessed as reduction in cell viability incubated for 72 hrs by Cell Titer Glo luminescent assay Antiproliferative activity against human RL95-2 habouring PTEN deletion mutant assessed as reduction in cell viability incubated for 72 hrs by Cell Titer Glo luminescent assay	[PMID: 35679512]
SMMC-7721	IC₅₀	0.661 μM Compound: GDC-0068	Cytotoxicity against human SMMC-7721 cells assessed as reduction in cell viability by MTT assay Cytotoxicity against human SMMC-7721 cells assessed as reduction in cell viability by MTT assay	[PMID: 32007668]
T47D	EC₅₀	443 nM Compound: Ipatasertib	Antiproliferative activity against human T47D cells assessed as reduction in cell viability incubated for 5 days by celltiter-glo assay Antiproliferative activity against human T47D cells assessed as reduction in cell viability incubated for 5 days by celltiter-glo assay	[PMID: 30996949]
T47D	IC₅₀	327.77 nM Compound: GDC-0068	Antiproliferative activity against human T47D habouring PIK3CA mutation/amplication assessed as reduction in cell viability incubated for 72 hrs by Cell Titer Glo luminescent assay Antiproliferative activity against human T47D habouring PIK3CA mutation/amplication assessed as reduction in cell viability incubated for 72 hrs by Cell Titer Glo luminescent assay	[PMID: 35679512]
TOV21G	IC₅₀	715.2 nM Compound: GDC-0068	Antiproliferative activity against human TOV-21G habouring PTEN deletion and PIK3CA mutation/amplication assessed as reduction in cell viability incubated for 72 hrs by Cell Titer Glo luminescent assay Antiproliferative activity against human TOV-21G habouring PTEN deletion and PIK3CA mutation/amplication assessed as reduction in cell viability incubated for 72 hrs by Cell Titer Glo luminescent assay	[PMID: 35679512]
ZR-75-1	EC₅₀	219 nM Compound: Ipatasertib	Antiproliferative activity against human ZR-75-1 cells assessed as reduction in cell viability incubated for 5 days by celltiter-glo assay Antiproliferative activity against human ZR-75-1 cells assessed as reduction in cell viability incubated for 5 days by celltiter-glo assay	[PMID: 30996949]
ZR-75-1	IC₅₀	1316 nM Compound: GDC-0068	Antiproliferative activity against human ZR-75-1 habouring PTEN deletion mutant assessed as reduction in cell viability incubated for 72 hrs by Cell Titer Glo luminescent assay Antiproliferative activity against human ZR-75-1 habouring PTEN deletion mutant assessed as reduction in cell viability incubated for 72 hrs by Cell Titer Glo luminescent assay	[PMID: 35679512]

In Vitro

Ipatasertib (10 µM; 12, 24 h) suppresses colon cancer cell proliferation by p53 irrespectively activating PUMA in vitro^[1].
Ipatasertib (1, 5, 10, 20 μM; 24 h/10 μM; 3, 6, 12, 24 h) up-regulates the expression level of PUMA in a concentration and time dependent manner in HCT116 cells^[1].
Ipatasertib increases the mRNA level of PUMA in HCT116 WT, p53^−/−, and DLD1 (p53 mutant) cells^[1].
Ipatasertib (10 µM; 24 h) induces apoptosis through PUMA/Bax pathway in HCT116 cells^[1].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Cell Viability Assay^[1]

Cell Line:	HCT116 WT, p53^−/−, and DLD1 (p53 mutant) cells
Concentration:	10 µM
Incubation Time:	12, 24 h
Result:	Decreased all the three cell lines viability.

Apoptosis Analysis^[1]

Cell Line:	HCT116 cells
Concentration:	10 µM
Incubation Time:	24 h
Result:	Induced apoptosis through PUMA/Bax pathway.

Western Blot Analysis^[1]

Cell Line:	HCT116 cells
Concentration:	1, 5, 10, 20 μM for 24 h/10 μM for 3, 6, 12, 24 h
Incubation Time:	24 h; 3, 6, 12, 24 h
Result:	Increased the level of PUMA in a concentration and time dependent manner.

In Vivo

Ipatasertib (30 mg/kg; p.o.; single daily for 15 consecutive days) exhibits PUMA-dependent antitumor activity in HCT116 WT and PUMA^−/− cells xenograft nude mice model^[1].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Animal Model:	HCT116 WT and PUMA^−/− cells xenograft nude mice model^[1].
Dosage:	30 mg/kg
Administration:	Oral gavage; single daily for 15 consecutive days.
Result:	Inhibited growth of tumors in a PUMA-dependent manner.

Masse moléculaire

458.00

Formule

C₂₄H₃₂ClN₅O₂

CAS No.

1001264-89-6

Appearance

Solid

Color

White to light yellow

SMILES

ClC1=CC=C([C@@H](CNC(C)C)C(N2CCN(C3=C([C@H](C)C[C@H]4O)C4=NC=N3)CC2)=O)C=C1

Livraison

Room temperature in continental US; may vary elsewhere.

Stockage

Powder	-20°C	3 years
	4°C	2 years
In solvent	-80°C	2 years
	-20°C	1 year

Solvant et solubilité

In Vitro:

DMSO : 100 mg/mL (218.34 mM; Need ultrasonic; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)

H₂O : 3.57 mg/mL (7.79 mM; ultrasonic and warming and heat to 60°C)

Preparing
Stock Solutions

Concentration Solvent Mass	1 mg	5 mg	10 mg

1 mM	2.1834 mL	10.9170 mL	21.8341 mL
5 mM	0.4367 mL	2.1834 mL	4.3668 mL
10 mM	0.2183 mL	1.0917 mL	2.1834 mL

View the Complete Stock Solution Preparation Table

* Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 2 years; -20°C, 1 year. When stored at -80°C, please use it within 2 years. When stored at -20°C, please use it within 1 year.

* Note: If you choose water as the stock solution, please dilute it to the working solution, then filter and sterilize it with a 0.22 μm filter before use.

Select the appropriate dissolution method based on your experimental animal and administration route.

For the following dissolution methods, please ensure to first prepare a clear stock solution using an In Vitro approach and then sequentially add co-solvents:
To ensure reliable experimental results, the clarified stock solution can be appropriately stored based on storage conditions. As for the working solution for in vivo experiments, it is recommended to prepare freshly and use it on the same day.
The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.

Protocol 1

Add each solvent one by one: 10% DMSO 40% PEG300 5% Tween-80 45% Saline
Solubility: ≥ 5 mg/mL (10.92 mM); Clear solution

This protocol yields a clear solution of ≥ 5 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (50.0 mg/mL) to 400 μL PEG300, and mix evenly; then add 50 μL Tween-80 and mix evenly; then add 450 μL Saline to adjust the volume to 1 mL.
Preparation of Saline: Dissolve 0.9 g sodium chloride in ddH₂O and dilute to 100 mL to obtain a clear Saline solution.
Protocol 2

Add each solvent one by one: 10% DMSO 90% (20% SBE-β-CD in Saline)
Solubility: ≥ 5 mg/mL (10.92 mM); Clear solution

This protocol yields a clear solution of ≥ 5 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (50.0 mg/mL) to 900 μL 20% SBE-β-CD in Saline, and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C, storage for one week): 2 g SBE-β-CD powder is dissolved in 10 mL Saline, completely dissolve until clear.
Protocol 3

Add each solvent one by one: 10% DMSO 90% Corn Oil
Solubility: ≥ 5 mg/mL (10.92 mM); Clear solution

This protocol yields a clear solution of ≥ 5 mg/mL (saturation unknown). If the continuous dosing period exceeds half a month, please choose this protocol carefully.
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (50.0 mg/mL) to 900 μL Corn oil, and mix evenly.

Pureté et documentation

Purity: 99.88%

Fiche technique (281 KB) SDS (396 KB)

COA (252 KB) HNMR (258 KB) RP-HPLC (294 KB) MS (82 KB)

Instruction de manipulation (2659 KB)

Références

[1]. Sun L, et al. Ipatasertib, a novel Akt inhibitor, induces transcription factor FoxO3a and NF-κB directly regulates PUMA-dependent apoptosis. Cell Death Dis. 2018 Sep 5;9(9):911. [Content Brief]

[2]. Blake JF, et al. Discovery and preclinical pharmacology of a selective ATP-competitive Akt inhibitor (GDC-0068) for the treatment of human tumors. J Med Chem. 2012 Sep 27;55(18):8110-27. [Content Brief]

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