Olaparib (AZD2281)

別名：Ku-0059436

製品コード：S1060 純度：99.99%

オラパリブ (Olaparib (AZD2281, KU0059436)) は選択的 PARP1/2 阻害剤であり、cell-free assay における IC50 はそれぞれ 5 nM および 1 nM です。タンキラーゼ-1 (Tankyrase-1) に対しては 1/300 の効果を示します。オラパリブは BRCA に変異をきたした細胞において、マイトファジー (mitophagy) に関連した顕著なオートファジー (mitophagy) を誘発します。

CAS No. 763113-22-0

サイズ	価格(税別)	在庫状況
10mM (1mL in DMSO)	JPY 41500	国内在庫あり
10mg	JPY 29500	国内在庫あり
25mg	JPY 41500	国内在庫あり
100mg	JPY 86500	国内在庫あり
1g	JPY 295500	国内在庫あり

代表番号: 045-509-1970\|電子メール：sales@selleck.co.jp よく尋ねられる質問

文献中Selleckの製品使用例（1201）

1/41

製品安全説明書

現在のバッチを見る：純度： 99.99%

99.99

Olaparib (AZD2281)関連製品

関連ターゲット	PARP1 PARP2 PARP3 Tankyrase-1 Tankyrase-2 PARP14 PARP7 TNKS1 TNKS2	もっと見る
関連製品	XAV-939 Veliparib (ABT-888) PJ34 HCl AG-14361 Iniparib (BSI-201) A-966492 G007-LK UPF 1069 AZD2461 Pamiparib ME0328 3-Aminobenzamide NMS-P118 Stenoparib (E7449) NVP-TNKS656 WIKI4 Benzamide BGP-15 2HCl NU1025 BYK204165 Fluzoparib (SHR-3162) Picolinamide	もっと見る
関連化合物ライブラリー	FDA-approved Drug Library Natural Product Library Apoptosis Compound Library DNA Damage/DNA Repair compound Library Cell Cycle compound library	もっと見る

シグナル伝達経路

PARPシグナル伝達経路

PARP阻害剤の選択性比較

阻害剤	Citation	PARP	PARP1	PARP2	PARP3	Tankyrase-1	Tankyrase-2	PARP14	PARP7	TNKS1	TNKS2	PARP10	その他
Veliparib (ABT-888)	243		++	+++
XAV-939	393					++	+++			++	+++
AG-14361	35		+++
A-966492	9		++++	+++
PJ34 HCl	44	++
UPF 1069	8		+	+
ME0328	6		+		+
XYL-1	0								++++
OUL232	0											++
Nesuparib	0		+++			+++	++++			+++	++++
M2912	0	++				++++				++++			Wnt
Venadaparib(IDX-1197)	0		++++	++++
Saruparib (AZD5305)	4		+++
DR2313	0		+	+
RBN012759	0							+++
Atamparib (RBN-2397)	1								++++
GeA-69	0							+
BYK204165	1		+	+
MN 64	0					++	+			++	+
RK-287107	0					++	++
4-Hydroxyquinazoline	0		+
Pamiparib	9		++++	++++
NMS-P118	6		++
Stenoparib (E7449)	8		++++	++++
Picolinamide	1	+
Benzamide	3	+
NVP-TNKS656	3						++				++
NU1025	2	+
WIKI4	3						++				++
G007-LK	13					+	++			+	++
Iniparib (BSI-201)	15		✔
3-Aminobenzamide	7	✔
AZD2461	7	✔
AZD9574	1	✔
Berberine chloride hydrate	2	✔											Bcl-XL,Bcl-2,c-IAP1
Fluzoparib (SHR-3162)	1	✔
Licochalcone D	0	✔											Caspase,Met,EGFR
HI-TOPK-032	0	✔											p53,ERK-RSK,TOPK
4',5,7-Trimethoxyflavone	0	✔											caspase-3
BGP-15 2HCl	3	✔
Berberine chloride	10	✔											cytochrome c,Topo II,Caspase-8

1. "+" indicates inhibitory effect. Increased inhibition is marked by a higher "+" designation. 2. "✔" indicates inhibitory effect, but without specific value.

Cell Data

Cell Lines	Assay Type	Concentration	Incubation Time	活性情報	PMID
SGC-7901	Growth Inhibition Assay	30 μM	48 h	Block oxaliplatin-induced cell death	25767076
Huh7	Function Assay	40 μM	24 h	Induces cell autophagy with DHMEQ	25072752
Hep3B	Function Assay	40 μM	24 h	Induces cell autophagy with DHMEQ	25072752
他の多くの細胞株試験データをご覧になる場合はこちらをクリックして下さい

生物活性

製品説明

特性

A potent PARP inhibitor (currently in late stage clinical trials).

Targets

PARP2 ^[1] (Cell-free assay)	PARP1 ^[1] (Cell-free assay)
1 nM	5 nM

In Vitro
In vitro	Olaparib would act against BRCA1 or BRCA2 mutations. Olaparib is not sensitive to tankyrase-1 (IC50 >1 μM). Olaparib could ablate the PARP-1 activity at concentrations of 30-100 nM in SW620 cells. Olaparib is hypersensitive to BRCA1-deficient cell lines (MDA-MB-463 and HCC1937), compared with BRCA1- and BRCA2-proficient cell lines (Hs578T, MDA-MB-231, and T47D). ^[1] Olaparib is strongly sensitive to KB2P cells due to suppression of base excision repair by PARP inhibition, which may result in the conversion of single-strand breaks to double-strand breaks during DNA replication, thus activating BRCA2-dependent recombination pathways. ^[2]
Kinase Assay	FlashPlate assay (96-well screening assay)
Kinase Assay	To columns 1 through 10, 1 μL of Olaparib (in DMSO) is added, and 1 μL DMSO only is added to the positive (POS) and negative (NEG) control wells (columns 11 and 12, respectively) of a pretreated FlashPlate. PARP-1 is diluted 1:40 in buffer (buffer B: 10% glycerol (v/v), 25 mM HEPES, 12.5 mM MgCl₂,50 mM KCl, 1 mM DTT, 0.01% NP-40 (v/v), pH 7.6) and 40 μL added to all 96 wells (final PARP-1 concentration in the assay is ~1 ng/μL). The plate is sealed and shaken at RT for 15 min. Following this, 10 μL of positive reaction mix (0.2 ng/μL of double-stranded oligonucleotide [M3/M4] DNA per well, 5 μM of NAD⁺ final assay concentration, and 0.075 μCi ³H-NAD⁺ per well) is added to the appropriate wells (columns 1-11). The negative reaction mix, lacking the DNA oligonucleotide, is added to column 12 (with the mean negative control value used as the background). The plate is resealed and shaken for a further 60 min at RT to allow the reaction to continue. Then, 50 μL of ice-cold acetic acid (30%) is added to each well to stop the reaction, and the plate is sealed and shaken for a further 60 min at RT. Tritiated signal bound to the FlashPlate is then determined in counts per minute (CPM) using the TopCount plate reader.
細胞実験	細胞株	Breast cancer cell lines including SW620 colon, A2780 ovarian, HCC1937, Hs578T, MDA-MB-231, MDA-MB-436, and T47D
	濃度	1-300 nM
	反応時間	7-14 days
	実験の流れ	The cytotoxicity of Olaparib is measured by clonogenic assay. Olaparib is dissolved in DMSO and diluted by culture media before use. The cells are seeded in six well plates and left to attach overnight. Then Olaparib is added at various concentrations and the cells are incubated for 7-14 days. After that the surviving colonies are counted for calculating the IC50.
実験結果図	Methods	Biomarkers	結果図	PMID
	Western Blot	DR5/CHOP γH2AX/H2AX pATM 53BP1 NF-kB pS6/S6		25531448
	Immunofluorescence	DNA damage γH2AX		27686740
	Growth inhibition assay	Cell viability		25531448
	ELISA	IL-8 GLP-1		28456021

In Vivo
In Vivo	Olaparib (10 mg/kg, p.o.) in Combination significantly suppresses tumor growth in SW620 xenografts. ^[1] Olaparib shows great response to Brca1^-/-;p53^-/- mammary tumors (50 mg/kg i.p. per day), while no responses to HR-deficient Ecad^-/-;p53^-/- mammary tumors. Olaparib even does not show dose-limiting toxicity in tumor-bearing mice. ^[3] Olaparib has been used to treat with BRCA mutated tumors, such as ovarian, breast and prostate cancers. Moreover, Olaparib shows selectively inhibition to ATM (Ataxia Telangiectasia Mutated)-deficient tumor cells, which indicates to be a potential agent for treating ATM mutant lymphoid tumors. ^[4]
動物実験	動物モデル	Brca1^-/-;p53^-/- mammary tumors are generated in K14cre;Brca1^F/F;p53^F/F mice.
	投与量	50 mg/kg
	投与経路	Administered via i.p. injection at 10 μL/g of body weight

NCT Number	Recruitment	Conditions	Sponsor/Collaborators	Start Date	Phases
臨床試験 (data from https://clinicaltrials.gov, updated on 2024-05-22)
NCT05128734	Not yet recruiting	Breast Cancer Triple Negative	AHS Cancer Control Alberta	July 1 2024	Phase 2
NCT05900895	Not yet recruiting	Metastatic Breast Cancer	Mary D Chamberlin\|Dartmouth-Hitchcock Medical Center	May 2024	Phase 1
NCT06377267	Recruiting	Ovarian Cancer	Vall d''Hebron Institute of Oncology	February 6 2024	Phase 2
NCT06065059	Recruiting	Breast Cancer\|Ovarian Cancer\|Pancreas Cancer\|Prostate Cancer\|BRCA1 Mutation\|BRCA-Mutated Ovarian Carcinoma\|BRCA-Associated Breast Carcinoma\|HRD Positive Advanced Ovarian Cancer	Tango Therapeutics Inc.	December 8 2023	Phase 1\|Phase 2

参考
[1] Menear KA, et al. J Med Chem, 2008, 51(20), 6581-6591. [2] Evers B, et al, Clin Cancer Res, 2008, 14(12), 3916-3925. [3] Rottenberg S, et al, Proc Natl Acad Sci U S A, 2008, 105(44), 17079-17084. [4] Weston VJ, et al, Blood, 2010, 116(22), 4578-4587. + 展開

参考

[4] Weston VJ, et al, Blood, 2010, 116(22), 4578-4587.

+ 展開

化学情報

分子量	434.46	化学式	C₂₄H₂₃FN₄O₃
CAS No.	763113-22-0	SDF	Download Olaparib (AZD2281) SDFをダウンロードする
Smiles	C1CC1C(=O)N2CCN(CC2)C(=O)C3=C(C=CC(=C3)CC4=NNC(=O)C5=CC=CC=C54)F
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 : 87 mg/mL ( (200.24 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。)

Water : Insoluble

Ethanol : 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
	Clear solution	10%DMSO 1 40%PEG300 Click to order 2 5%Tween 80 Click to order 3 45%ddH2O	9.0mg/ml (20.72mM)	Taking the 1 mL working solution as an example, add 100 μL of 90 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 450 μL of ddH2O to adjust the volume to 1 mL. The mixed solution should be used immediately for optimal results.	投与溶液組成計算機
Clear solution	10% DMSO 1 40%PEG300 Click to order 2 5%Tween 80 Click to order 3 45%ddH2O	11.0mg/ml (25.32mM)	Taking the 1 mL working solution as an example, add 100 μL of 110 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 450 μL of ddH2O to adjust the volume to 1 mL. The mixed solution should be used immediately for optimal results.
Clear solution	10%DMSO 1 90%Corn oil	10.0mg/ml (23.02mM)	Taking the 1 mL working solution as an example, add 100 μL of 100 mg/ml clear DMSO stock solution to 900 μL of corn oil and mix evenly. The mixed solution should be used immediately for optimal results.
Clear solution	5%DMSO 1 40%PEG300 Click to order 2 5%Tween 80 Click to order 3 50%ddH2O	7.5mg/ml (17.26mM)	Taking the 1 mL working solution as an example, add 50 μL of 150 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.

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。

技術サポート

ストックの作り方、阻害剤の保管方法、細胞実験や動物実験の際に注意すべき点など、製品を取扱う時に問い合わせが多かった質問に対しては取扱説明書でお答えしています。

Handling Instructions

他に質問がある場合は、お気軽にお問い合わせください。

* 必須

* 大学・企業名 大学・企業名を記入してください

* 名前 名前を記入してください

* 電子メール 電子メール・アドレスを記入してください 有効なメールアドレスを入力してください

電話番号

* 内容 お問い合わせ内容をご入力ください

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):