(R)-(-)-Gossypol (AT-101) acetic acid

製品コード：S2812 純度：99.81%

(R)-(-)-Gossypol (AT-101) acetic acid, the R-(-) enantiomer of Gossypol acetic acid, binds with Bcl-2, Bcl-xL and Mcl-1 with K_i of 0.32 μM, 0.48 μM and 0.18 μM in cell-free assays; does not inhibit BIR3 domain and BID. AT-101 simultaneously triggers apoptosis and a cytoprotective type of autophagy. Phase 2.

(R)-(-)-Gossypol (AT-101) acetic acid化学構造

CAS No. 866541-93-7

サイズ	価格(税別)	在庫状況
10mM (1mL in DMSO)	JPY 28500	国内在庫あり
10mg	JPY 22000	国内在庫あり
50mg	JPY 70500	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（17）

カスタマーフィードバック5个实验数据

製品安全説明書

現在のバッチを見る：純度： 99.81%

99.81

(R)-(-)-Gossypol (AT-101) acetic acid関連製品

関連ターゲット	Bcl-2 Bcl-B Bcl-w Bcl-xL Mcl-1 Bax Bfl-1 Bad Bcl-xL	もっと見る
関連化合物ライブラリー	Autophagy Compound Library Apoptosis Compound Library Ferroptosis Compound Library Pyroptosis Compound Library Mitochondria-Targeted Compound Library	もっと見る

シグナル伝達経路

Bcl-2シグナル伝達経路

Bcl-2阻害剤の選択性比較

生物活性

製品説明

Targets

Mcl-1 ^[1] (Cell-free assay)	Bcl-2 ^[1] (Cell-free assay)	Bcl-xL ^[1] (Cell-free assay)
0.18 μM(Ki)	0.32 μM(Ki)	0.48 μM(Ki)

In Vitro
In vitro	AT-101 inhibits a panel of different lymphoproliferative malignancies with IC50 ranged from 1.2 μM to 7.4 μM. AT-101 (10 μM) disrupts the Δψm in a concentration- and time-dependent manner in a diffuse large B-cell and in mantle cell lymphoma lines. AT-101 (1 μM or 2 μM) combined with carfilzomib (6 nM or 10 nM) induces apoptosis in HBL-2 and Granta cell lines. ^[2] AT-101 (20 μM for 24 hours) results in a median 72% apoptosis and down-regulation of Mcl-1 in CLL lymphocytes in both suspension culture as well as stromal coculture. Stromal cells express undetectable levels of antiapoptotic but high levels of activated ERK and AKT proteins and has low or no apoptosis with AT-101. ^[3] AT-101 induces apoptosis in a time- and dose-dependent fashion, with ED50 values of 1.9 mM and 2.4 mM in Jurkat T and U937 cells, respectively. AT-101 (10 μM) combined with radiation (32 Gy) induces more apoptosis than radiation alone and exceeds the sum of the effects caused by the single agent treatments. AT-101 activates SAPK/JNK in a dose- and time-dependent manner. ^[4] AT-101 (10 µM) induces apoptosis through activation of caspase-9, -3, and -7 in VCaP Cells. AT-101 (10 µM) decreases Bcl-2 and Mcl-1 expression in VCaP cells. ^[5] AT-101 (< 20 μM) is able to inhibit the growth of multiple myeloma cells despite the stimulatory growth effects provided by stromal cells in the bone marrow milieu. AT-101 (10 μM) induces apoptosis in multiple myeloma cells via the activation of caspases 3, caspases 9 and PARP. AT-101 (10 μM) promotes apoptosis in multiple myeloma cells by disrupting the Bax/Bcl-2 ratio and the mitochondrial membrane potential. ^[6]
Kinase Assay	Fluorescence-Polarization-Based Binding Assay
Kinase Assay	For competitive binding experiments, Bcl-2 protein (40 nM) and FAM-Bid peptide (2.5 nM) are preincubated in the assay buffer (100 mM potassium phosphate, pH 7.5; 100 μg/mL bovine gamma globulin; 0.02% sodium azide, 5 μL of a solution in DMSO of AT101 is added to the Bcl-2/FAM-Bid solution in Dynex 96-well, black, round-bottom plates to produce a final volume of 125 μL. For each experiment, a control containing Bcl-2 and Flu-Bid peptide (equivalent to 0% inhibition), and another control containing only FAM-Bid, are included on eachassay plate. After 4 hours incubation, the polarization values in milipolarization units (mP) weremeasured at an excitation wavelength at 485 nm and an emission wavelength at 530 nm using the Ultra plate reader. IC50,the inhibitor concentration at which 50% of bound peptide is displaced, is determined from the plot using nonlinear leastsquares analysis and curve fitting performed using GraphPad Prizm 4 software. The unlabeled Bid BH3 peptide is used as the positive control. PF for Bcl-xL protein, Bak BH3 peptide labeled with 6-carboxyfluorescein succinimidyl ester (FAM-Bak) instead of the FAM-Bim to maximize the signal. It is determined that FAM-Bak has a Kd of 6 nM to Bcl-xL protein. The competitive binding assay for Bcl-xL is same as that for Bcl-2 with the following exceptions. 30 nM of Bcl-xL protein and 2.5 nM of FAM-Bak peptide in the following assay buffer: 50 mM Tris-Bis, pH 7.4 and 0.01% bovine gamma globulin. PF for Mcl-1 protein, FAM-Bid peptide and human Mcl-1 protein are used. It is determined that FAM-Bid peptide binds to human Mcl-1 protein with a Kd of 1.71 nM. The competitive binding assays for Mcl-1 are performed in the same manner as that for Bcl-2 with the following exceptions. 5 nM Mcl-1 and 1 nM Flu-Bid peptide in the following assay buffer: 25 mM Tris, pH 8.0; 150 mM NaCl and 0.05% Pluronic acid
細胞実験	細胞株	RL, H9, SKI, HBL-2, Granta and JJN-3 cell lines
	濃度	~10 μM
	反応時間	72 hours
	実験の流れ	Cells are counted and resuspended at an approximate concentration of 3×10⁵ cells/well in a 24-well plate. AT-101 is diluted in DMSO that is maintained at a final concentration of less than 0.5%. Concentrations of AT-101 from 1 nM to 10 μM are used in most experiments. Following incubation at 37 ℃ in a 5% CO₂ humidified incubator, 100 μL from each well is transferred to a 96-well opaque-walled plate; cell-Titer-Glo Reagent is added in a 1:1 ratio. Contents are mixed for 2 minutes on an orbital shaker to induce cell lysis. The plates are allowed to incubate at room temperature for 10 minutes before recording luminescence with a Synergy HT Multi-Detection Microplate Reader. In the schedule dependency experiments, serial dilutions of each drug are prepared in ratios relative to their IC50. Cells are preincubated with AT-101 for up to 72 hours, while 4-HC is added for a 24-hour period, being added at time 0, 24 hours, and 48 hours from the start of incubation. Each experiment is performed in triplicate and repeated at least twice.
実験結果図	Methods	Biomarkers	結果図	PMID
	Growth inhibition assay	Cell viability		24824755
	Western blot	BNIP3 Smac / Cyt C p53 / Cox IV p-AKT / AKT APE1 / Bcl-2 / p53 / p-p53 / NF-κB		24824755

In Vivo
In Vivo	AT-101 is still detectable in plasma with average concentrations of 0.49 μM for the 35 mg/kg group and 0.39 μM for the 200 mg/kg group in SCID beige mice bearing RL-DLBCL xenograft. AT-101 peak plasma concentration is observed after 30 minutes of administration of the drug in both the dose levels, with the 200 mg/kg group showing a plasma average concentration almost 4 times greater than the 35 mg/kg group (7.88 μM and 27.78 μM respectively) in SCID beige mice. AT-101 (25 mg/kg to 100 mg/kg, orally) indefinitely results in earlier onset of weight loss equivalent to more than 10% of the pretreatment weight and death in SCID beige mice. AT-101 (35 mg/kg, orally per day for 10 days) plus intraperitoneal cyclophosphamide (Cy) and intraperitoneal rituximab (R) show significantitumor volume control compared to any other treatment group. ^[2] AT-101 (15 mg/kg, p.o., 5 days/week) as a single agent in intact mice significantly reduces the development of VCaP tumor growth compared to untreated tumors at weeks 2 to 6. AT-101 in combination with surgical castration delays the onset of androgen-independent VCaP tumor growth compared to castration-only or AT-101-only groups in mice. ^[5]
動物実験	動物モデル	SCID beige mice bearing RL-DLBCL xenograft
	投与量	100 mg/kg
	投与経路	Oral gavage

NCT Number	Recruitment	Conditions	Sponsor/Collaborators	Start Date	Phases
臨床試験 (data from https://clinicaltrials.gov, updated on 2024-01-11)
NCT05338931	Recruiting	B-cell Non Hodgkin Lymphoma	AbClon	March 15 2022	Phase 1\|Phase 2
NCT00934076	Withdrawn	Carcinoma Non Small Cell Lung	University of Alabama at Birmingham\|Ascenta Therapeutics	February 2010	Phase 1
NCT00561197	Terminated	Locally Advanced Esophageal or GE Junction Cancer	Ascenta Therapeutics	August 2007	Phase 1\|Phase 2

参考
[1] Wang G, et al. J Med Chem. 2006, 49(21), 6139-6142. [2] Paoluzzi L, et al. Blood, 2008, 111(11), 5350-5358. [3] Balakrishnan K, et al. Blood, 2009, 113(1), 149-153. [4] Zerp SF, et al. Radiat Oncol, 2009, 23(4), 47. [5] Loberg RD, et al. Neoplasia, 2007, 9(12), 1030-1037. [6] Kline MP, et al. Exp Hematol, 2008, 36(5), 568-576. + 展開

参考

+ 展開

化学情報

分子量	578.61	化学式	C₃₀H₃₀O₈.C₂H₄O₂
CAS No.	866541-93-7	SDF	Download (R)-(-)-Gossypol (AT-101) acetic acid SDFをダウンロードする
Smiles	CC1=CC2=C(C(=C(C(=C2C(C)C)O)O)C=O)C(=C1C3=C(C4=C(C=C3C)C(=C(C(=C4C=O)O)O)C(C)C)O)O.CC(=O)O
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 ( (172.82 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 : 100 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。

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:
Is S2812 (-)-gossypol or another enantiomer?

回答
S2812 AT101 is R-(–)-gossypolacetic acid.

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C1=C0/X	C1:	LOG(C1):
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C8=C7/X	C8:	LOG(C8):