Uprosertib (GSK2141795)

別名：GSK795

製品コード：S7492 純度：99.84%

Uprosertib (GSK2141795, GSK795) is a selective, ATP-competitive, and orally bioavailable Akt inhibitor with IC50 of 180 nM, 328 nM, and 38 nM for Akt 1, 2 and 3, respectively. Phase 2.

CAS No. 1047634-65-0

サイズ	価格(税別)	在庫状況
10mM (1mL in DMSO)	JPY 29500	国内在庫あり
5mg	JPY 22000	国内在庫あり
25mg	JPY 59500	国内在庫あり
100mg	JPY 134500	国内在庫あり

代表番号: 045-509-1970\|電子メール：[email protected] よく尋ねられる質問

文献中Selleckの製品使用例（13）

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製品安全説明書

現在のバッチを見る：純度： 99.84%

99.84

Uprosertib (GSK2141795)関連製品

関連ターゲット	Akt1 Akt2 Akt3	もっと見る
関連製品	MK-2206 2HCl Perifosine SC79 Capivasertib (AZD5363) GSK690693 Ipatasertib (GDC-0068) Triciribine (API-2) CCT128930 Afuresertib (GSK2110183) A-674563 HCl AT7867 Oridonin Akti-1/2 PHT-427 TIC10 (ONC201) Miransertib (ARQ 092) HCl AT13148 Miransertib (ARQ-092) SC66 Deguelin ML-9 HCl	もっと見る
関連化合物ライブラリー	Kinase Inhibitor Library PI3K/Akt Inhibitor Library Apoptosis Compound Library Cell Cycle compound library NF-κB Signaling Compound Library	もっと見る

シグナル伝達経路

Aktシグナル伝達経路

Akt阻害剤の選択性比較

Cell Data

Cell Lines	Assay Type	Incubation Time	活性情報	PMID
Sf9	Function assay	40 mins	Inhibition of full length human AKT2 expressed in Sf9 cells assessed as reduction in substrate phosphorylation using biotin-ahx-ARKRERAYSFGHHA-amide substrate and [gamma-33P]ATP incubated for 40 mins by top count microplate scintillation counting method, IC50=0.01585μM	ChEMBL
Sf9	Function assay	40 mins	Inhibition of full length human AKT1 expressed in Sf9 cells assessed as reduction in substrate phosphorylation using biotin-ahx-ARKRERAYSFGHHA-amide substrate and [gamma-33P]ATP incubated for 40 mins by top count microplate scintillation counting method, IC50=0.001995μM	ChEMBL
OVCAR8	Cytotoxicity assay	72 hrs	Cytotoxicity against human OVCAR8 cells assessed as reduction in cell viability incubated for 72 hrs by SRB assay, IC50=0.54μM	31301565
HCT116	Antiproliferative assay	72 hrs	Antiproliferative activity against human HCT116 cells after 72 hrs by SRB assay, IC50=0.72μM	31298542
PTEN-null LNCAP	Function assay	1 hr	Inhibition of Akt in human PTEN-null LNCAP cells assessed as suppression in PRAS40 phosphorylation after 1 hr by ELISA analysis, IC50=0.07563μM	27089211
HCT116	Growth inhibition assay	72 hrs	Growth inhibition of human HCT116 cells over-expressing DHODH at 2 times antiproliferative IC50 after 72 hrs in absence of uridine by MTT assay	31301565
OVCAR8	Cytotoxicity assay	72 hrs	Cytotoxicity against human OVCAR8 cells assessed as reduction in cell viability incubated for 72 hrs by SRB assay, IC50=0.54μM	31301565
HCT116	Antiproliferative assay	72 hrs	Antiproliferative activity against human HCT116 cells after 72 hrs by SRB assay, IC50=0.72μM	31298542
HCT116	Growth inhibition assay	72 hrs	Growth inhibition of human HCT116 cells over-expressing DHODH at 2 times antiproliferative IC50 after 72 hrs in absence of uridine by MTT assay	31301565
RPMI8226	Antiproliferative assay		Antiproliferative activity against human RPMI8226 cells assessed as reduction in cell viability, IC50=0.538μM	31301565
MM1S	Antiproliferative assay		Antiproliferative activity against human MM1S cells assessed as reduction in cell viability, IC50=0.032μM	31301565
CEM/C1	Antiproliferative assay		Antiproliferative activity against human CEM/C1 cells assessed as reduction in cell viability, IC50=0.03μM	31301565
HUT78	Antiproliferative assay		Antiproliferative activity against human HUT78 cells assessed as reduction in cell viability, IC50=0.378μM	31301565
KB-3-1	qHTS assay		P-glycoprotein substrates identified in KB-3-1 adenocarcinoma cell line, qHTS therapeutic library screen	ChEMBL
JVM2	Antiproliferative assay		Antiproliferative activity against human JVM2 cells assessed as reduction in cell viability, IC50=0.293μM	31301565
OVCAR8	Antiproliferative assay		Antiproliferative activity against human OVCAR8 cells, IC50=0.24μM	31298542
MOLT4	Antiproliferative assay		Antiproliferative activity against human MOLT4 cells assessed as reduction in cell viability, IC50=0.066μM	31301565
MV4-11	Antiproliferative assay		Antiproliferative activity against human MV4-11 cells assessed as reduction in cell viability, IC50=0.635μM	31301565
LNCAP	Antiproliferative assay		Antiproliferative activity against human LNCAP cells, IC50=0.07μM	31298542
U937	Antiproliferative assay		Antiproliferative activity against human U937 cells assessed as reduction in cell viability, IC50=0.101μM	31301565
OVCAR8	Antiproliferative assay		Antiproliferative activity against human OVCAR8 cells, IC50=0.24μM	31298542
JVM2	Antiproliferative assay		Antiproliferative activity against human JVM2 cells assessed as reduction in cell viability, IC50=0.293μM	31301565
HUT78	Antiproliferative assay		Antiproliferative activity against human HUT78 cells assessed as reduction in cell viability, IC50=0.378μM	31301565
RPMI8226	Antiproliferative assay		Antiproliferative activity against human RPMI8226 cells assessed as reduction in cell viability, IC50=0.538μM	31301565
MV4-11	Antiproliferative assay		Antiproliferative activity against human MV4-11 cells assessed as reduction in cell viability, IC50=0.635μM	31301565
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生物活性

製品説明

Uprosertib (GSK2141795, GSK795) is a selective, ATP-competitive, and orally bioavailable Akt inhibitor with IC50 of 180 nM, 328 nM, and 38 nM for Akt 1, 2 and 3, respectively. Phase 2.

Targets

Akt3 ^[1] (Cell-free assay)	Akt1 ^[1] (Cell-free assay)	Akt2 ^[1] (Cell-free assay)
38 nM	180 nM	328 nM

In Vitro
In vitro	Uprosertib inhibits multiple AKT substrate phosphorylation levels, including GSK3β, PRAS40, FOXO and Caspase 9 in both BT474 and LNCaP cells. Uprosertib preferentially inhibits the proliferation of human cancer cells lines with AKT pathway activation. In LNCaP, BT474, A3 and I9.2 cells lines, Uprosertib also causes cell cycle arrest. ^[2] In both SKOV3 and PEO4 cells, Uprosertib causes growth-arrest as single agent, and enhances induced apoptosis. ^[3]
Kinase Assay	Selectivity profiling experiments
Kinase Assay	The lysates (5 mg of total protein each) are preincubated with 0 (DMSO control), 2.5 nM, 25 nM, 250 nM, 2.5 μM or 25 μM free compound (GSK690693 or GSK2141795) on an end-over-end shaker for 45 min at 4 °C. Subsequently, lysates are incubated with beads (coupled Akt probe or kinobeads) for 1 h at 4 °C, for both qualitative and quantitative experiments. The beads are washed with 1× CP buffer and collected by centrifugation. Bound proteins are eluted with 2× NuPAGE LDS sample buffer, and eluates are reduced and alkylated by 50 mM dithiothreitol and 55 mM iodoacetamide.
細胞実験	細胞株	A panel of 290 cells lines
	濃度	~30 μM
	反応時間	3 d
	実験の流れ	Cell lines are typically grown in RPMI 160 medium containing 10% FBS. Some cell lines are grown in media specified by the vendor. A 3-day proliferation assay using CellTiter-Glo is performed to measure the growth inhibition by the compounds at 0–30 µM. Cell growth is determined relative to untreated (DMSO) controls. EC50's are calculated from inhibition curves using a 4- or 6-parameter fitting algorithm in the Assay Client application.

In Vivo
In Vivo	In mice bearing BT474 breast tumor xenografts, Uprosertib (100 mg/kg, p.o.) results 61% tumor growth inhibition. In mice bearing SKOV3 ovarian tumor xenografts, Uprosertib (30 mg/kg, p.o.) results 61% tumor growth inhibition. ^[2]
動物実験	動物モデル	Mice bearing either BT474 or SKOV3 tumors
	投与量	100 mg/kg
	投与経路	p.o.

NCT Number	Recruitment	Conditions	Sponsor/Collaborators	Start Date	Phases
臨床試験 (data from https://clinicaltrials.gov, updated on 2024-05-22)
NCT01958112	Terminated	Cervical Cancer	Dana-Farber Cancer Institute\|Novartis\|National Comprehensive Cancer Network	October 2013	Phase 2
NCT01941927	Completed	Melanoma	Adil Daud\|National Comprehensive Cancer Network\|University of California San Francisco	September 10 2013	Phase 2
NCT01266954	Completed	Solid Tumours	GlaxoSmithKline	June 1 2010	Phase 1
NCT01138085	Completed	Cancer	GlaxoSmithKline	May 4 2010	Phase 1

参考
[1] Pachl F, et al. J Proteome Res. 2013, 12(8), 3792-3800. [2] Dumble M, et al. PLoS One. 2014, 9(6):e100880. [3] Cheraghchi-Bashi A, et al. Oncotarget. 2015, 6(39), 41736-41749.

参考

化学情報

分子量	429.25	化学式	C₁₈H₁₆C_l2F₂N₄O₂
CAS No.	1047634-65-0	SDF	Download Uprosertib (GSK2141795) SDFをダウンロードする
Smiles	CN1C(=C(C=N1)Cl)C2=C(OC(=C2)C(=O)NC(CC3=CC(=C(C=C3)F)F)CN)Cl
保管	3年-20°C粉	溶液の保管冷凍と解凍の繰り返しを避けるため小分けにしてください	1年-80°Cin solvent
保管	3年-20°C粉	溶液の保管冷凍と解凍の繰り返しを避けるため小分けにしてください	１ケ月-20°Cin solvent

In vitro
Batch:

DMSO : 85 mg/mL ( (198.01 mM)；吸湿したDMSOは溶解度を減少させます。新しいDMSOをご使用ください。)

Ethanol : 85 mg/mL

Water : Insoluble

モル濃度計算器

in vivo
Batch:

Add solvents to the product individually and in order.

投与溶液組成計算機

実験計算

モル濃度計算器

質量	濃度	体積	分子量
=	×	×

希釈計算器分子量計算器

投与溶液組成計算機(クリア溶液)

ステップ１：実験データを入力してください。（実験操作によるロスを考慮し、動物数を1匹分多くして計算・調製することを推奨します）

投与量 mg/kg 動物平均体重 g 投与体積（動物毎）μL 動物数匹

ステップ２：投与溶媒の組成を入力してください。（ロット毎に適した溶解組成が異なる場合があります。詳細については弊社までお問い合わせください）

% DMSO + % + % Tween 80 + % ddH₂O

%DMSO+ %

計算結果：

投与溶媒濃度： mg/ml;

DMSOストック溶液調製方法： mg 試薬を μL DMSOに溶解する（濃度 mg/mL, 注：濃度が当該ロットのDMSO溶解度を超える場合はご連絡ください。 )

投与溶媒調製方法：Take μL DMSOストック溶液に μL PEG300，を加え、完全溶解後μL Tween 80，を加えて完全溶解させた後 μL ddH₂O，を加え完全に溶解させます。

投与溶媒調製方法：μL DMSOストック溶液に μL Corn oil，を加え、完全溶解。

注意：１.ストック溶液に沈殿、混濁などがないことをご確認ください；
２.順番通りに溶剤を加えてください。次のステップに進む前に溶液に沈殿、混濁などがないことを確認してから加えてください。ボルテックス、ソニケーション、水浴加熱など物理的な方法で溶解を早めることは可能です。

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