Capivasertib (AZD5363)

Capivasertib (AZD5363) potently inhibits all isoforms of Akt(Akt1/Akt2/Akt3) with IC50 of 3 nM/8 nM/8 nM in cell-free assays, similar to P70S6K/PKA and lower activity towards ROCK1/2. Phase 2.

CAS No. 1143532-39-1

サイズ	価格(税別)	在庫状況
10mM (1mL in DMSO)	JPY 35200	国内在庫あり
5mg	JPY 22000	国内在庫あり
25mg	JPY 70500	国内在庫あり
100mg	JPY 175500	国内在庫あり
1g	JPY 370500	国内在庫なし(納期7~10日)

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（127）

製品安全説明書

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Capivasertib (AZD5363)と併用されることが多い化合物

Everolimus

Capivasertib and Everolimus inhibits the proliferation of homozygous H2189Y mutant cells.

Wu X, et al. Cancer Biol Ther. 2018 Jul 3;19(7):584-589.

Alpelisib (BYL719)

Capivasertib and Alpelisib are recently approved in combination with the estrogen receptor degrader fulvestrant for the treatment of ER+ advanced breast cancer.

Alves CL, et al. Int J Mol Sci. 2023 Feb 24;24(5):4522.

Enzalutamide

Capivasertib and Enzalutamide show synergistic decreases in cell proliferation and induce cell-cycle arrest and apoptosis in prostate cancer cell lines LNCaP and C4-2.

Toren P, et al. Eur Urol. 2015 Jun;67(6):986-990.

Paclitaxel

Capivasertib addition to first-line paclitaxel therapy for triple-negative breast cancer (TNBC) results in significantly longer progression-free survival (PFS) and overall survival (OS).

Schmid P, et al. J Clin Oncol. 2020 Feb 10;38(5):423-433.

Palbociclib

Capivasertib and Palbociclib synergistically inhibit the proliferation of luminal androgen receptor (LAR) triple-negative breast cancer (TNBC) cells.

Kim GM, et al. Cancer Res (2022) 82 (4_Supplement): PD3-07.

Capivasertib (AZD5363)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 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 Miltefosine AT13148 Uprosertib (GSK2141795) 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	Concentration	Incubation Time	活性情報	PMID
LNCaP	Function Assay	5 μM	0-24 h	induces AKTS473 and AKTT308 phosphorylation in a time dependent manner	23966621
C4-2	Function Assay	5 μM	0-24 h	induces AKTS473 and AKTT308 phosphorylation in a time dependent manner	23966621
LNCaP	Function Assay	5 μM	0-24 h	inhibits phosphorylation of the distal AKT-pathway biomarkers including PRAS40, eIF4E, 4E-BP1, mTOR, and P70 S6 kinase in a time-dependent manner	23966621
C4-2	Function Assay	5 μM	0-24 h	inhibits phosphorylation of the distal AKT-pathway biomarkers including PRAS40, eIF4E, 4E-BP1, mTOR, and P70 S6 kinase in a time-dependent manner	23966621
LNCaP	Growth Inhibition Assay	1-10000 nM	0-3 d	inhibits cell viability dose dependently	23966621
C4-2	Growth Inhibition Assay	1-10000 nM	0-3 d	inhibits cell viability dose dependently	23966621
LNCaP	Growth Inhibition Assay	100-5000 nM	72 h	increases the fraction of cells undergoing cell death	23966621
C4-2	Growth Inhibition Assay	100-5000 nM	72 h	increases the fraction of cells undergoing cell death	23966621
PC-3	Function Assay	0.5/1/10 μM	48 h	downregulates the phosphorylation of downstream pathway proteins in a dose-dependent manner	23258740
DU145	Function Assay	0.5/1/10 μM	48 h	downregulates the phosphorylation of downstream pathway proteins in a dose-dependent manner	23258740
LNCaP	Cell Viability Assay	0-1000 nM	0-4 d	reduced LNCaP cell viability in a dose- and time-dependent manner	23258740
PC-3	Function Assay	10 μM	12 h	induces autophagy	23258740
PC-9	Function Assay	1/5/10 μM	4/24 h	increases AKT phosphorylation	24957682
NCI-H522	Function Assay	1/5/10 μM	4/24 h	increases AKT phosphorylation	24957682
MR49F	Growth Inhibition Assay	0-5 μM	48 h	inhibits cell growth in a dose dependent manner	25151012
MR49C	Growth Inhibition Assay	0-5 μM	48 h	inhibits cell growth in a dose dependent manner	25151012
SKBR3	Growth Inhibition Assay	0-1.35 μM	5 d	enhances the growth inhibition of AZD8931	26095475
KPL4	Growth Inhibition Assay	0-1.35 μM	5 d	enhances the growth inhibition of AZD8931	26095475
BT474c	Growth Inhibition Assay	0-1.35 μM	5 d	enhances the growth inhibition of AZD8931	26095475
HCC1954	Growth Inhibition Assay	0-1.35 μM	5 d	enhances the growth inhibition of AZD8931	26095475
TamR	Growth Inhibition Assay	400 nM	6 d	increased drug sensitivity of 4-OHT and fulvestrant	26351323
T74D LTED	Growth Inhibition Assay	100 nM	6 d	increased drug sensitivity of 4-OHT and fulvestrant	26351323
ZR75 LTED	Growth Inhibition Assay	100 nM	6 d	increased drug sensitivity of 4-OHT and fulvestrant	26351323
MCF7 LTED	Growth Inhibition Assay	200 nM	6 d	increased drug sensitivity of 4-OHT and fulvestrant	26351323
1%MCF7	Growth Inhibition Assay	400 nM	6 d	increased drug sensitivity of 4-OHT and fulvestrant	26351323
T74D	Growth Inhibition Assay	100 nM	6 d	increased drug sensitivity of 4-OHT and fulvestrant	26351323
ZR75	Growth Inhibition Assay	100 nM	6 d	increased drug sensitivity of 4-OHT and fulvestrant	26351323
MCF7	Growth Inhibition Assay	200 nM	6 d	increased drug sensitivity of 4-OHT and fulvestrant	26351323
MDA-MB-468	Function assay		2 hrs	Inhibition of Akt in human MDA-MB-468 cells assessed as inhibition of GSK3beta phosphorylation after 2 hrs by laser scanning cytometry, IC50 = 0.089 μM.	23394218
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 = 0.3368 μM.	27089211
HCT116	Antiproliferative assay		72 hrs	Antiproliferative activity against human HCT116 cells after 72 hrs by SRB assay, IC50 = 5.2 μM.	27089211
OVCAR8	Antiproliferative assay		72 hrs	Antiproliferative activity against human OVCAR8 cells after 72 hrs by SRB assay, IC50 = 7.27 μM.	27089211
SNU-638	Growth Inhibition Assay			IC50=4.523 μM	24088382
SNU-1	Growth Inhibition Assay			IC50=5.258 μM	24088382
SNU-601	Growth Inhibition Assay			IC50=5.938 μM	24088382
SNU-668	Growth Inhibition Assay			IC50=6.003 μM	24088382
HS746T	Growth Inhibition Assay			IC50=6.084 μM	24088382
KATO III	Growth Inhibition Assay			IC50=7.267 μM	24088382
SNU-484	Growth Inhibition Assay			IC50=7.392 μM	24088382
OCUM-1	Growth Inhibition Assay			IC50=14.515 μM	24088382
SNU-16	Growth Inhibition Assay			IC50=11.097 μM	24088382
NUGC-3	Growth Inhibition Assay			IC50=21.873 μM	24088382
AZ521	Growth Inhibition Assay			IC50=25.448 μM	24088382
SNU-216	Growth Inhibition Assay			IC50=30 μM	24088382
NUGC-4	Growth Inhibition Assay			IC50=30 μM	24088382
SNU-5	Growth Inhibition Assay			IC50=30 μM	24088382
GTL-16	Growth Inhibition Assay			IC50=30 μM	24088382
MKN74	Growth Inhibition Assay			IC50=30 μM	24088382
PAMC82	Growth Inhibition Assay			IC50=30 μM	24088382
SNU-620	Growth Inhibition Assay			IC50=3.384 μM	24088382
MKN1	Growth Inhibition Assay			IC50=2.421 μM	24088382
23132/87	Growth Inhibition Assay			IC50=1.671 μM	24088382
NCI-N87	Growth Inhibition Assay			IC50=1.037 μM	24088382
AGS	Growth Inhibition Assay			IC50=0.552 μM	24088382
IM95m	Growth Inhibition Assay			IC50=0.51 μM	24088382
HGC27	Growth Inhibition Assay			IC50=0.445 μM	24088382
PC-9	Growth Inhibition Assay			IC50=9.3 (±1.2) μM	24957682
NCI-H522	Growth Inhibition Assay			IC50=11.3 (±2.7) μM	24957682
LNCaP	Function assay			Inhibition of Akt in PTEN-deficient human LNCaP cells assessed as phosphorylation of GSK3beta, IC50 = 0.06 μM.	23394218
LNCaP	Function assay			Inhibition of Akt in PTEN-deficient human LNCaP cells assessed as phosphorylation of PRAS40, IC50 = 0.22 μM.	23394218
BT474c	Function assay			Inhibition of Akt in human BT474c cells harboring HER2+/PIK3CA double mutant assessed as phosphorylation of PRAS40, IC50 = 0.31 μM.	23394218
MDA-MB-468	Function assay			Inhibition of Akt in PTEN-deficient human MDA-MB-468 cells assessed as phosphorylation of GSK3beta, IC50 = 0.38 μM.	23394218
MDA-MB-468	Function assay			Inhibition of Akt in PTEN-deficient human MDA-MB-468 cells assessed as phosphorylation of PRAS40, IC50 = 0.39 μM.	23394218
BT474c	Function assay			Inhibition of Akt in human BT474c cells harboring HER2+/PIK3CA double mutant assessed as phosphorylation of GSK3beta, IC50 = 0.76 μM.	23394218
RT4	Function assay			Inhibition of PKA in TSC1 deficient human RT4 cells assessed as S6 phosphorylation, IC50 = 1 μM.	23394218
RT4	Function assay			Inhibition of P70S6K in TSC1 deficient human RT4 cells assessed as S6 phosphorylation, IC50 = 5 μM.	23394218
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
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
NB1643	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for NB1643 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
Rh41	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Rh41 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
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生物活性

製品説明

Capivasertib (AZD5363) potently inhibits all isoforms of Akt(Akt1/Akt2/Akt3) with IC50 of 3 nM/8 nM/8 nM in cell-free assays, similar to P70S6K/PKA and lower activity towards ROCK1/2. Phase 2.

特性

Moderate preclinical tolerability, and PD characteristics of an AKT inhibitor. Distinct profile from other AKT inhibitors in clinical development.

Targets

Akt1 ^[1] (Cell-free assay)	Akt2 ^[1] (Cell-free assay)	Akt3 ^[1] (Cell-free assay)	ROCK2 ^[1] (Cell-free assay)
3 nM	8 nM	8 nM	56 nM

In Vitro
In vitro	AZD5363 is a potent Akt inhibitor with IC50 of 3 nM, 8 nM and 8 nM for Akt1, Akt2 and Akt3, respectively. ^[1] AZD5363 inhibits phosphorylation of AKT substrates in cells with a potency of approximately 0.3 to 0.8 μM. AZD5363 inhibits the proliferation of 41 of 182 solid and hematologic tumor cell lines with a potency of < 3 μM. ^[2] Activating mutations in PIK3CA, loss or inactivation of tumor suppressor PTEN, or HER2 amplification all are significantly predictive of responsiveness to AZD5363. Additionally, correlation is also seen between the RAS mutation status of cell lines and resistance to AZD5363. ^[1]
Kinase Assay	Caliper Off-Chip Incubation Mobility Shift assay
Kinase Assay	The ability of AZD5363 and other compounds to inhibit the activity of AKT1, AKT2, and AKT3 is evaluated by the Caliper Off-Chip Incubation Mobility Shift assay. Active recombinant AKT1, AKT2, or AKT3 are incubated with a 5-FAM-labeled custom-synthesized peptide substrate together with increasing concentrations of inhibitor. Final reactions contained 1 to 3 nM AKT1, AKT2, or AKT3 enzymes; 1.5 mM peptide substrate; ATP at K _m for each AKT isoform; 10 mM MgCl₂, 4 mM DTT, 100 mM HEPES, and 0.015% Brij-35. The reactions are incubated at room temperature for 1 hour and stopped by the addition of buffer containing 100 mM HEPES, 0.015% Brij-35 solution, 0.1% coating reagent, 40 mM EDTA, and 5% DMSO. Plates are then analyzed using a Caliper LC3000, allowing for separation of peptide substrate and phosphorylated product by electrophoresis with subsequent detection and quantification of laser induced fluorescence.
細胞実験	細胞株	182 solid and hematologic tumor cell lines
	濃度	~30 μM
	反応時間	72 hours
	実験の流れ	Cell proliferation assay is determined by 2 methods, MTS and Sytox Green. Briefly, cells are seeded in 96-well plates and incubated overnight at 37 ℃, 5% CO₂. Cells are then exposed to concentrations of AZD5363 ranging from 30 to 0.003μM for 72 hours. For the MTS endpoint, cell proliferation is measured by the CellTiter AQueous Non-Radioactive Cell Proliferation Assay reagent in accordance with the manufacturer's protocol. For the Sytox Green endpoint, Sytox Green nucleic acid dye diluted in TBS-EDTA buffer is added to cells (final concentration of 0.13 μM) and the number of dead cells detected using an Acumen Explorer. Cells are then permeabilized by the addition of saponin (0.03% final concentration, diluted in TBS-EDTA buffer), incubated overnight and a total cell count measured. Predose measurements are made for both MTS and Sytox Green endpoints, and concentration needed to reduce the growth of treated cells to half that of untreated cells values are determined using absorbance readings (MTS) or live cell counts.
実験結果図	Methods	Biomarkers	結果図	PMID
	Western blot	pAKT / AKT / pGSK3β / GSK3β HER3 / pHER3 / HER2 / pHER2 / pPRAS40 / pS6 / p-4EBP1 / pFOXO / pERK / PARP / Cleaved PARP		26998062
	Immunofluorescence	p-Chk2 / γ-H2AX		29879757
	Growth inhibition assay	Cell viability		29879757

In Vivo
In Vivo	Oral dosing of AZD5363 (100, 300 mg/kg) to nude mice causes dose- and time-dependent reduction of PRAS40, GSK3β, and S6 phosphorylation in BT474c xenografts, reversible increases in blood glucose concentrations, and dose-dependent decreases in 2[¹⁸F]fluoro-2-deoxy-d-glucose (¹⁸F-FDG) uptake in U87-MG xenografts. Chronic oral dosing of AZD5363 (130, 200, and 300 mg/kg) causes dose-dependent growth inhibition of xenografts derived from various tumor types, including HER2+ breast cancer models that are resistant to trastuzumab. AZD5363 also significantly enhances the antitumor activity of docetaxel, lapatinib, and trastuzumab in breast cancer xenografts. ^[2]
動物実験	動物モデル	Female nude mice and male SCID mice with BT474c, U87MG, KPL-4, HCC-1187 xenografts.
	投与量	130 mg/Kg - 300 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 2024-01-11)
NCT03310541	Completed	Breast Cancer\|Prostate Cancer\|Advanced Solid Tumors	Memorial Sloan Kettering Cancer Center	October 11 2017	Phase 1
NCT01992952	Active not recruiting	Estrogen Receptor Positive Breast Cancer	Velindre NHS Trust\|AstraZeneca\|Cenduit LLC\|Covance\|Cardiff and Vale University Health Board	May 2014	Phase 1\|Phase 2
NCT02338622	Completed	Advanced Cancer	Royal Marsden NHS Foundation Trust\|Institute of Cancer Research United Kingdom\|AstraZeneca	March 31 2014	Phase 1
NCT02121639	Completed	Prostate Cancer	University Hospital Southampton NHS Foundation Trust\|AstraZeneca\|Cancer Research UK	January 29 2014	Phase 1\|Phase 2
NCT02077569	Completed	Invasive Breast Cancer	University of Nottingham\|AstraZeneca\|Cancer Research UK\|National Cancer Research Network	January 2014	Phase 2
NCT01692262	Completed	Metastatic Castrate-Resistant Prostate Cancer (mCRPC)\|Efficacy\|Safety and Tolerability\|Pharmacokinetics\|Pharmacodynamics\|Tumour Response.	AstraZeneca	November 2012	Phase 1

参考
[1] Addie M, et al. J Med Chem, 2013, 26. [2] Davies BR, et al. Mol Cancer Ther, 2012, 11(4), 873-887.

参考

化学情報

分子量	428.92	化学式	C₂₁H₂₅ClN₆O₂
CAS No.	1143532-39-1	SDF	Download Capivasertib (AZD5363) SDFをダウンロードする
Smiles	C1CN(CCC1(C(=O)NC(CCO)C2=CC=C(C=C2)Cl)N)C3=NC=NC4=C3C=CN4
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个月-20°Cin solvent

In vitro
Batch:

DMSO : 86 mg/mL ( (200.5 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 : 20 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。

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):