VER155008

VER155008 is a potent Hsp70 family inhibitor with IC50 of 0.5 μM, 2.6 μM, and 2.6 μM in cell-free assays for HSP70, HSC70, and GRP78 (HSPA5, Bip), respectively, >100-fold selectivity over HSP90. VER155008 inhibits autophagy and causes reduced levels of HSP90 client proteins.

CAS No. 1134156-31-2

サイズ	価格(税別)	在庫状況
10mg	JPY 22000	国内在庫あり
50mg	JPY 61000	国内在庫あり
1g	JPY 595500	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

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製品安全説明書

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VER155008関連製品

関連ターゲット	HSP40 HSP70 HSP90 HSP105 HSF1	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	Incubation Time	活性情報	PMID
BL21 DE3	Function assay	10 mins	Inhibition of GRP78 (26 to 636 residues) (unknown origin) expressed in Escherichia coli BL21 DE3 cells pre-incubated for 10 mins before FITC-NRLLLTG fluorescent peptide addition in presence of 10 uM ADP followed by further incubation for 2 hrs by fluoresc, IC50=0.8μM	31129054
HCT116	Function assay	24 hrs	Inhibition of HSP70 in human HCT116 cells assessed as reduction of He2 protein levels after 24 hrs by Western blot	19256508
HCT116	Function assay	24 hrs	Inhibition of HSP70 in human HCT116 cells assessed as reduction of Raf1 protein levels after 24 hrs by Western blot	19256508
HCT116	Cytotoxicity assay		Cytotoxicity against human HCT116 cells by SRB assay, GI50=5μM	19256508
HCT116	Antiproliferative assay		Antiproliferative activity against human HCT116 cells, GI50=5μM	21526763
BT474	Function assay		Binding affinity to Hsp70 nucleotide binding domain in human BT474 cells, IC50=10.4μM	20608738
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生物活性

製品説明

VER155008 is a potent Hsp70 family inhibitor with IC50 of 0.5 μM, 2.6 μM, and 2.6 μM in cell-free assays for HSP70, HSC70, and GRP78 (HSPA5, Bip), respectively, >100-fold selectivity over HSP90. VER155008 inhibits autophagy and causes reduced levels of HSP90 client proteins.

Targets

HSP70 ^[1] (Cell-free assay)	HSC70 ^[1] (Cell-free assay)	GRP78 ^[1] (Cell-free assay)
0.5 μM	2.6 μM	2.6 μM

In Vitro
In vitro	VER-155008 inhibits the proliferation of human breast and colon cancer cell lines BT474, MB-468, HCT116, and HT29 with GI50s in the range 5.3-14.4 μM, and induces Hsp90 client protein degradation in both HCT116 and BT474 cells.^[1] In the 8505C and FRO cells, VER-155008 reduces the cell viability and elevates the percentage of dead cells in a time- and dose- dependent manner.^[2] VER-155008 causes a dose-dependent inhibition of cytokine-dependent AML cell proliferation.^[3] VER-155008 shows an effective inhibition of cell proliferation in A549 and H1975 cells. ^[4]
Kinase Assay	Hsc70, Hsp70 and Grp78 ﬂuorescence polarisation (FP) assay
Kinase Assay	The FP assay for Hsp70 is conducted in aqueous buffer consisting of 100 mM Tris pH 7.4, 150 mM KCl and 5 mM CaCl2, in a final assay volume of 100 µl, using 96 well black polystyrene high bind plates with a Fusion plate reader. N⁶-(6-amino)hexyl-ATP-5-FAM and the in-house protein preparation of GST-HSP70 3-382 have final concentrations in the assay of 20 nM and 400 nM, respectively. Compounds are tested as 10-point IC50s, with a final DMSO concentration of 5%. Assay mixtures are incubated for 3 h prior to reading on the Fusion (ex 485 nm; em 535 nm). The data is fitted using a 4 parameter logistical data model by XLFit 4. The FP assay for Hsc70 and Grp78 is carried out as described for Hsp70 using the same N6 -(6-amino)hexyl-ATP-5-FAM as the FP probe with the following modiﬁcations. For Hsc70, the protein and probe concentrations are 0.3 μM and 20 nM, respectively with a 30 min incubation at 22℃ while for Grp78, the protein and probe concentrations are 2 μM and 10 nM, respectively with a 2 h incubation at 22℃. The K^D for the FAM-ATP probe was 0.24 μM for Hsc70 and 2 μM for Grp78.
細胞実験	細胞株	BT474, MB-468, HCT116, and HT29 cells
	濃度	50 μM
	反応時間	72 h
	実験の流れ	All cell lines are grown in DMEM/10% FCS with GlutaMAX-I in a humidified atmosphere of 5% CO₂ in air. Cell proliferation is determined using the sulforhodamine B (SRB) assay.
実験結果図	Methods	Biomarkers	結果図	PMID
	Western blot	Hsp70 / AR		28691182
	Immunofluorescence	Blimp-1		28842558
	Growth inhibition assay	Cell viability		28053100

In Vivo
In Vivo	In HCT116 tumor bearing mice, VER-155008 (25 or 40 mg/kg, i.v.) demonstrates rapid metabolism and clearance, along with tumor levels below the predicted pharmacologically active level.^[1]
動物実験	動物モデル	HCT116 tumor bearing
	投与量	40 mg/kg
	投与経路	i.v.

参考
[1] Massey AJ, et al. Cancer Chemother Pharmacol. 2010, 66(3), 535-545. [2] Kim SH, et al. Biochem Biophys Res Commun. 2014, 454(1), 36-41. [3] Reikvam H, et al. Expert Opin Incestiq Drugs. 2013, 22(5), 551-563. [4] Wen W, et al. Exp Biol Med (Maywood). 2014, 239(5), 638-645. [5] Williamson DS, et al. J Med Chem. 2009, 52(6), 1510-1513. + 展開

参考

+ 展開

化学情報

分子量	556.4	化学式	C₂₅H₂₃Cl₂N₇O₄
CAS No.	1134156-31-2	SDF	Download VER155008 SDFをダウンロードする
Smiles	C1=CC(=CC=C1COCC2C(C(C(O2)N3C4=NC=NC(=C4N=C3NCC5=CC(=C(C=C5)Cl)Cl)N)O)O)C#N
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 : 100 mg/mL ( (179.72 mM)； Warmed with 50℃ water bath; 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。

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):