Abexinostat (PCI-24781)

別名：CRA-024781

製品コード：S1090 純度：98.89%

Abexinostat (PCI-24781, CRA-024781) is a novel pan-HDAC inhibitor mostly targeting HDAC1 with K_i of 7 nM, modest potent to HDACs 2, 3, 6, and 10 and greater than 40-fold selectivity against HDAC8. Phase 1/2.

CAS No. 783355-60-2

サイズ	価格(税別)	在庫状況
10mM (1mL in DMSO)	JPY 40500	国内在庫あり
5mg	JPY 25500	国内在庫あり
10mg	JPY 48000	国内在庫あり
50mg	JPY 145500	国内在庫なし(納期7~10日)
1g	JPY 585000	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（23）

カスタマーフィードバック3例

製品安全説明書

現在のバッチを見る：純度： 98.89%

98.89

Abexinostat (PCI-24781)関連製品

関連ターゲット	HDAC1 HDAC2 HDAC3 HDAC4 HDAC5 HDAC6 HDAC7 HDAC8 HDAC9 HDAC10 HDAC11 HD1 HD2	もっと見る
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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

HDACシグナル伝達経路

HDAC阻害剤の選択性比較

Cell Data

Cell Lines	Assay Type	Incubation Time	活性情報	PMID
HeLa	Function assay	2 hrs	Inhibition of dye-labeled tracer binding to HDAC10 (unknown origin) transfected in human HeLa cells measured after 2 hrs by nano-luciferase reporter gene-based BRET assay, IC50=0.007943μM	30964290
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
BT-37	qHTS assay		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for BT-37 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
U-2 OS	qHTS assay		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for U-2 OS 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
BT-12	qHTS assay		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for BT-12 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
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
Rh30	qHTS assay		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Rh30 cells	29435139
Rh41	qHTS assay		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Rh41 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
DAOY	qHTS assay		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for DAOY cells	29435139
NB-EBc1	qHTS assay		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for NB-EBc1 cells	29435139
SJ-GBM2	qHTS assay		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for SJ-GBM2 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
MG 63 (6-TG R)	qHTS assay		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for MG 63 (6-TG R) 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
Saos-2	qHTS assay		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for Saos-2 cells	29435139
OHS-50	qHTS assay		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for OHS-50 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

Targets

HDAC1 ^[1] (Cell-free assay)	HDAC3/SMRT ^[1]	HDAC6 ^[1]	HDAC2 ^[1] (Cell-free assay)	HDAC10 ^[1]	もっとクリックする
7 nM(Ki)	8.2 nM(Ki)	17 nM(Ki)	19 nM(Ki)	24 nM	もっとクリックする

In Vitro
In vitro	PCI-24781 exhibits potent antitumor activity against a variety of tumor cell lines with GI50 ranging from 0.15 μM to 3.09 μM. PCI-24781 also has an antiproliferative effect on HUVEC endothelial cells with GI50 of 0.43 μM. PCI-24781 treatment causes dose-dependent accumulation of both acetylated histones and acetylated tubulin in HCT116 or DLD-1 cells, induces expression of p21, and leads to PARP cleavage and accumulation of the γH2AX. ^[1] Inhibition of HDAC enzymes by PCI-24781 leads to a significant reduction in the transcription of genes specifically associated with HR, including RAD51. Consistent with inhibition of HR, PCI-24781 treatment results in a decreased ability to perform homology directed repair of I-SceI-induced chromosome breaks in transfected CHO cells. ^[2] PCI-24781 induces S phase depletion, G2 cell cycle arrest, and apoptosis in soft tissue sarcoma (STS) cells. PCI-24781 induces Rad51 transcriptional repression in STS cells potentially mediated via enhanced E2F1 binding to the Rad51 proximal promoter. ^[3] PCI-24781 induces caspase and reactive oxygen species-dependent apoptosis through NF-κB mechanisms in Hodgkin lymphoma and non-Hodgkin lymphoma cell lines. ^[4]
Kinase Assay	HDAC Activity
Kinase Assay	HDAC activity is measured using a continuous trypsin-coupled assay. For inhibitor characterization, measurements are done in a reaction volume of 100 μL using 96-well assay plates. For each isozyme, the HDAC protein in reaction buffer [50 mM HEPES, 100 mM KCl, 0.001% Tween 20, 5% DMSO (pH 7.4), supplemented with bovine serum albumin at concentrations of 0% (HDAC1), 0.01% (HDAC2, 3, 8, and 10), or 0.05% (HDAC6)] is mixed with PCI-24781 at various concentrations and allowed to incubate for 15 minutes. Trypsin is added to a final concentration of 50 nM, and acetyl-Gly-Ala-(N-acetyl-Lys)-AMC is added to a final concentration of 25 μM (HDAC1, 3, and 6), 50 μM (HDAC2 and 10), or 100 μM (HDAC8) to initiate the reaction. Negative control reactions are done in the absence of PCI-24781 in replicates of eight. Reactions are monitored in a fluorescence plate reader. After a 30-minute lag time, the fluorescence is measured over a 30-minute time frame using an excitation wavelength of 355 nm and a detection wavelength of 460 nm. The increase in fluorescence with time is used as the measure of the reaction rate. Inhibition constants K_i(app) are obtained using the program BatchKi.
細胞実験	細胞株	HCT116, HCT-15, BT-549, NCI-H226, CWR-22RV1, MCF-7, NCI-PC3, DLD-1, SKOV-3, and OVCAR-3
	濃度	Dissolved in DMSO, final concentrations ~10 μM
	反応時間	48, 72, 96, or 120 hours
	実験の流れ	Cells are cultured for at least two doubling times, and growth is monitored at the end of PCI-24781 exposure using an Alamar blue fluorometric cell proliferation assay. PCI-24781 is assayed in triplicate wells in 96-well plates at nine concentrations using half-log intervals ranging from 0.0015 μM to 10 μM. The final DMSO concentration in each well is 0.15%. The concentration required to inhibit cell growth by 50% (GI50) and 95% confidence intervals are estimated from nonlinear regression using a four-parameter logistic equation.

In Vivo
In Vivo	Administration of PCI-24781 at 200 mg/kg once daily every other day (q.o.d.) significantly inhibits the growth of HCT116 and DLD-1 xenografts in mice by 69% and 59%, respectively. Administration of PCI-24781 at 20 mg/kg, 40 mg/kg, 80 mg/kg, or 160 mg/kg once daily for 4 consecutive days followed by 3 days without treatment each week (q.d. × 4 per week) in the HCT116 model causes inhibition of tumor growth by 48%, 57%, 82.2%, or 80.0%, respectively. ^[1]
動物実験	動物モデル	Female BALB/c nu/nu mice implanted s.c. with HCT116 and DLD-1 tumor cells
	投与量	~200 mg/kg
	投与経路	Administered via i.v.

NCT Number	Recruitment	Conditions	Sponsor/Collaborators	Start Date	Phases
臨床試験 (data from https://clinicaltrials.gov, updated on 2024-05-22)
NCT05698524	Recruiting	Recurrent High Grade Glioma\|Anaplastic Astrocytoma\|Anaplastic Oligodendroglioma\|Glioblastoma\|Gliosarcoma	University of Nebraska\|Xynomic Pharmaceuticals Inc.	June 26 2023	Phase 1
NCT03934567	Recruiting	Lymphoma Follicular	Xynomic Pharmaceuticals Inc.	April 22 2020	Phase 2
NCT03939182	Active not recruiting	Diffuse Large B-cell Lymphoma\|Mantle Cell Lymphoma	Memorial Sloan Kettering Cancer Center\|Janssen Scientific Affairs LLC\|Xynomic Pharmaceuticals Inc.	May 29 2019	Phase 1
NCT03600441	Active not recruiting	Follicular Lymphoma	Xynomic Pharmaceuticals Inc.	August 27 2018	Phase 2
NCT01543763	Active not recruiting	Metastatic Solid Tumors	Pamela Munster\|Pharmacyclics LLC.\|Novartis\|Xynomic Pharmaceuticals Inc.\|GlaxoSmithKline Research and Education Foundation for Cardiovascular Disease\|University of California San Francisco	June 25 2012	Phase 1

参考
[1] Buggy JJ, et al. Mol Cancer Ther, 2006, 5(5), 1309-1317. [2] Adimoolam S, et al. Proc Natl Acad Sci U S A, 2007, 104(49), 19482-19487. [3] Lopez G, et al. Clin Cancer Res, 2009, 15(10), 3472-3483. [4] Bhalla S, et al. Clin Cancer Res, 2009, 15(10), 3354-3365. + 展開

参考

[4] Bhalla S, et al. Clin Cancer Res, 2009, 15(10), 3354-3365.

+ 展開

化学情報

分子量	397.42	化学式	C₂₁H₂₃N₃O₅
CAS No.	783355-60-2	SDF	Download Abexinostat (PCI-24781) SDFをダウンロードする
Smiles	CN(C)CC1=C(OC2=CC=CC=C21)C(=O)NCCOC3=CC=C(C=C3)C(=O)NO
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:

5%TFA : 3 mg/mL

DMSO : Insoluble ( 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

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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