Onalespib (AT13387)

製品コード：S1163 純度：99.94%

Onalespib (AT13387) is a selective potent Hsp90 inhibitor with IC50 of 18 nM in A375 cells, displays a long duration of anti-tumor activity. Phase 2.

CAS No. 912999-49-6

サイズ	価格(税別)	在庫状況
10mM (1mL in DMSO)	JPY 66000	国内在庫あり
5mg	JPY 40500	国内在庫あり
50mg	JPY 145500	国内在庫あり
1g	JPY 448500	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（28）

カスタマーフィードバック3个实验数据

製品安全説明書

現在のバッチを見る：純度： 99.94%

99.94

Onalespib (AT13387)関連製品

関連ターゲット	HSP40 HSP70 HSP90 HSP105 HSF1	もっと見る
関連製品	Tanespimycin (17-AAG) Luminespib (NVP-AUY922) Elesclomol (STA-4783) Ganetespib (STA-9090) Alvespimycin (17-DMAG) HCl VER155008 BIIB021 NVP-BEP800 KRIBB11 SNX-2112 HA15 Zelavespib (PU-H71) HSP990 (NVP-HSP990) NMS-E973 Apoptozole XL888 PF-04929113 (SNX-5422) KNK437 Teprenone TRC051384 VER-50589 Rocaglamide VER-49009 Pimitespib (TAS-116) JG98 DTHIB KW-2478	もっと見る
関連化合物ライブラリー	Kinase Inhibitor Library Angiogenesis Related compound Library TGF-beta/Smad compound library Cytoskeletal Signaling Pathway Compound Library Anti-Cardiovascular Disease Compound Library	もっと見る

シグナル伝達経路

HSP (HSP90)シグナル伝達経路

HSP (HSP90)阻害剤の選択性比較

Cell Data

Cell Lines	Assay Type	Concentration	Incubation Time	活性情報	PMID
human HCT116 cells	Function assay	30 nM	18 h	Induction of apoptosis in human HCT116 cells assessed as reduction of Raf-1 level at 30 nM after 18 hrs by immunoblotting	20662534
human HCT116 cells	Function assay	30 nM	18 h	Induction of apoptosis in human HCT116 cells assessed as reduction of CDK4 level at 30 nM after 18 hrs by immunoblotting	20662534
human HCT116 cells	Function assay	10 nM	18 h	Induction of apoptosis in human HCT116 cells assessed as upregulation of Hsp70 level at 10 nM after 18 hrs by immunoblotting	20662534
PANC1	Function assay	1 uM	36 hrs	Inhibition of HSP90alpha in human PANC1 cells assessed as up-regulation of Hsp70 at 1 uM after 36 hrs by Western blot analysis	30351001
PANC1	Function assay	1 uM	36 hrs	Inhibition of HSP90alpha in human PANC1 cells assessed as akt degradation at 1 uM after 36 hrs by Western blot analysis	30351001
human HCT116 cells	Proliferation assay		48 h	Antiproliferative activity against human HCT116 cells after 48 hrs by MTT assay, IC50=0.08 μM	24763261
human SKBR3 cells	Proliferation assay		48 h	Antiproliferative activity against human SKBR3 cells after 48 hrs by MTT assay, IC50=0.14 μM	24763261
human MCF7 cells	Proliferation assay		48 h	Antiproliferative activity against human MCF7 cells after 48 hrs by MTT assay, IC50=0.28 μM	24763261
human A231 cells	Proliferation assay		48 h	Antiproliferative activity against human A231 cells after 48 hrs by MTT assay, IC50=1.01 μM	24763261
GIST430	Cytotoxicity assay		7 days	Cytotoxicity against imatinib-resistant human GIST430 cells assessed as decrease in cell viability after 7 days by alamar blue assay, IC50=0.034μM.	26844689
GIST48	Cytotoxicity assay		7 days	Cytotoxicity against imatinib-resistant human GIST48 cells assessed as decrease in cell viability after 7 days by alamar blue assay, IC50=0.055μM.	26844689
MCF7	Antiproliferative assay		72 hrs	Antiproliferative activity against human MCF7 cells incubated for 72 hrs by MTT assay, IC50=0.032μM.	29028527
SKBR3	Antiproliferative assay		72 hrs	Antiproliferative activity against human SKBR3 cells incubated for 72 hrs by MTT assay, IC50=0.045μM.	29028527
NCI-H3122	Antiproliferative assay		72 hrs	Antiproliferative activity against human NCI-H3122 cells after 72 hrs by SRB assay, IC50=0.052μM.	29698859
MCF7	Antiproliferative assay		72 hrs	Antiproliferative activity against human MCF7 cells after 72 hrs by MTT assay, IC50=0.29μM.	30784881
NCI-H1299	Antiproliferative assay		72 hrs	Antiproliferative activity against human NCI-H1299 cells after 72 hrs by MTT assay, IC50=0.37μM.	30784881
A549	Antiproliferative assay		72 hrs	Antiproliferative activity against human A549 cells after 72 hrs by MTT assay, IC50=0.44μM.	30784881
Vero E6	Function assay		48 hrs	IC50 for antiviral activity against SARS-CoV-2 in the Vero E6 cell line at 48 h by immunofluorescence-based assay (detecting the viral NP protein in the nucleus of the Vero E6 cells), IC50=0.15488μM.	32353859
human HCT116 cells	Cytotoxic assay			Cytotoxicity against human HCT116 cells by Alamar blue assay, IC50=0.048 μM	20662534
TC32	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for TC32 cells	29435139
DAOY	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for DAOY 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
A673	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for A673 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
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
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
OHS-50	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for OHS-50 cells	29435139
RD	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for RD cells	29435139
NB1643	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for NB1643 cells	29435139
A673	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for A673 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
BT-12	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for BT-12 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
BT-37	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for BT-37 cells	29435139
TC32	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for TC32 cells	29435139
U-2 OS	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for U-2 OS cells	29435139
Rh41	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for Rh41 cells	29435139
RD	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for RD cells	29435139
Rh18	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for Rh18 cells	29435139
Rh30	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for Rh30 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
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生物活性

製品説明

Onalespib (AT13387) is a selective potent Hsp90 inhibitor with IC50 of 18 nM in A375 cells, displays a long duration of anti-tumor activity. Phase 2.

Targets

HSP90 ^[1]
(Cell-free assay)

18 nM

In Vitro
In vitro	The K_d for AT13387 binding is 0.7 nM. This compares to a K_d of 6.7 nM for the binding of the ansamycin 17-AAG to the same site. The mean stoichio metry of binding for AT13387 is 1.03. The inhibition of a number of isolated kinases by AT13387 is also investigated including CDK 1, CDK 2, CDK4, FGFR3, PKB-b, JAK2, VEGFR2, PDGFRβ and Aurora B. None of the tested kinases are significantly inhibited at concentrations below 30 μM. AT13387 is a potent inhibitor of the proliferat ion and survival of many different cell lines (such as MES-SA cell line) from a variety of different tumor types. Across a panel of 30 tumor cell lines, AT13387 potently inhibits cell proliferation with GI50 values in the range 13-260 nM. AT13387 inhibits proliferation of the non-tumorigenic human prostate epithelial cell line PNT2 with a GI50 value of 480 nM. ^[2]
Kinase Assay	HSP90 competition isothermal calorimetry
Kinase Assay	K_d values for AT13387 binding to HSP90 are determined with a competition Isothermal Calorimetry (ITC) format. ITC experiments are performed on a Micro Cal VP-ITC at 25 °C in a buffer comprising 25 mM Tris, 100 mM NaCl, 1 mM MgCl₂ and 1 mM Tris(2-carboxy- ethyl)phosphine at pH 7.4 in order to maintain the higher affinit
細胞実験	細胞株	A375, 22RV1 and T474 cells
	濃度	1 μM
	反応時間	4 hours
	実験の流れ	The human cell lines including A375, 22RV1, T474, DU1 45, LNCa P, MCF-7, DA-MB-468 are seeded into 96-well plates before the addition of AT13387 in 0.1% (v/v) DMSO. GI50 are determined using a 10-point dose response curve for three cell doubling times. After AT13387 incubation 10% (v/v), Alamar blueis added, and cells are incubated for a further 4 hours. Fluorescence is read.
実験結果図	Methods	Biomarkers	結果図	PMID
	Western blot	HSP90 / HSP70 EGFR / p-EGFR / AKT / p-AKT / ERK / p-ERK / S6 / p-S6 AXL / c-Myc / p-Mnk1 / Mnk1 / p-eIF4E / eIF4E		28679777
	Growth inhibition assay	Cell viability		28679777

In Vivo
In Vivo	When given on an intermittent basis, AT13387 could be tolerated at doses of up to 70 mg/kg twice weekly or 90 mg/kg once weekly. Body weight loss in mice does not exceed 20% before recovering in all cases except one, and loss is highest following the second dose. Tumor growth inhibition is similar in NCI-H1975 for both dosing regimens. The maintenance of antitumor effects with such a prolonged off-treatment period is consistent with the extended pharmacodynamic action of AT13387 observed for mutant EGFR and other biomarkers in vitro and in vivo and the extended retention of AT13387 in tumors. ^[2]
動物実験	動物モデル	Athymic BALB /c mice
	投与量	80 mg/kg
	投与経路	Intraperitoneal adminis tration

NCT Number	Recruitment	Conditions	Sponsor/Collaborators	Start Date	Phases
臨床試験 (data from https://clinicaltrials.gov, updated on 2024-01-11)
NCT02898207	Completed	Metastatic High Grade Fallopian Tube Serous Adenocarcinoma\|Metastatic Malignant Solid Neoplasm\|Metastatic Primary Peritoneal Serous Adenocarcinoma\|Metastatic Triple-Negative Breast Carcinoma\|Platinum-Resistant Fallopian Tube Carcinoma\|Platinum-Resistant Ovarian Carcinoma\|Platinum-Resistant Primary Peritoneal Carcinoma\|Recurrent Breast Carcinoma\|Recurrent High Grade Fallopian Tube Serous Adenocarcinoma\|Recurrent High Grade Ovarian Serous Adenocarcinoma\|Recurrent Primary Peritoneal High Grade Serous Adenocarcinoma\|Recurrent Triple-Negative Breast Carcinoma\|Refractory Fallopian Tube Serous Adenocarcinoma\|Refractory Ovarian Serous Adenocarcinoma\|Refractory Primary Peritoneal Serous Adenocarcinoma\|Refractory Triple-Negative Breast Carcinoma\|Unresectable High Grade Fallopian Tube Serous Adenocarcinoma\|Unresectable Malignant Solid Neoplasm\|Unresectable Primary Peritoneal Serous Adenocarcinoma	National Cancer Institute (NCI)	May 19 2017	Phase 1

参考
[1] Lyons J, et al.Poser A217. [2] Graham B, et al. Cancer Sci. 2012, 103(3), 522-527.

参考

化学情報

分子量	409.52	化学式	C ₂₄H₃₁N₃O₃
CAS No.	912999-49-6	SDF	Download Onalespib (AT13387) SDFをダウンロードする
Smiles	CC(C)C1=CC(=C(C=C1O)O)C(=O)N2CC3=C(C2)C=C(C=C3)CN4CCN(CC4)C
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 : 25 mg/mL ( (61.04 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

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

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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

よくある質問（FAQ）

質問1:
How to prepare the compound for in vivo studies?

回答
S1163 AT13387 can be dissolved in 2% DMSO/30% PEG 300/ddH2O at 10 mg/ml as a clear solution. But after stayed for about 1 hour, the precipitation will goes out. So it is recommended to be prepared before use.

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):