Venetoclax (ABT-199)

別名：GDC-0199

製品コード：S8048 純度：99.97%

Venetoclax (ABT-199, GDC-0199) is a Bcl-2-selective inhibitor with K_i of <0.01 nM in cell-free assays, >4800-fold more selective versus Bcl-xL and Bcl-w, and no activity to Mcl-1. Venetoclax is reported to induce cell growth suppression, apoptosis, cell cycle arrest, and autophagy in triple negative breast cancer MDA-MB-231 cells. Phase 3.

CAS No. 1257044-40-8

サイズ	価格(税別)	在庫状況
10mM (1mL in DMSO)	JPY 55500	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 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

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製品安全説明書

現在のバッチを見る：純度： 99.97%

99.97

Venetoclax (ABT-199)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
関連製品	ABT-737 Navitoclax (ABT-263) Obatoclax Mesylate (GX15-070) S63845 A-1210477 TW-37 A-1331852 A-1155463 Dihydrochloride UMI-77 AZD5991 (R)-(-)-Gossypol (AT-101) acetic acid Sabutoclax WEHI-539 HA14-1 MIK665 (S64315) Obatoclax (GX15-070) Gambogic Acid Marinopyrrole A (Maritoclax) BAI1 A-1155463 BTSA1 S55746 Ruxotemitide (LTX 315) BAM7 BDA-366	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

阻害剤	Citation	Bcl-2	Bcl-B	Bcl-w	Bcl-xL	Mcl-1	Bax	Bfl-1	Bcl-xL	その他
ABT-737	378	+++	+	++	+++ +++				+++ +++
Navitoclax (ABT-263)	376	++++		++++	++++ ++++				++++ ++++
Obatoclax Mesylate (GX15-070)	109	++
TW-37	45	++			+ +	++			+ +
(R)-(-)-Gossypol (AT-101) acetic acid	19	++			++ ++	+++			++ ++
HA14-1	6	+
Sabutoclax	10	++			++ ++	++		+	++ ++
A-1155463	12				+++ +++				+++ +++
APG-2575 (lisaftoclax)	0	+++			+++ +++				+++ +++
Gossypol	3	+			++ ++				++ ++	3α-hydroxysteroid dehydrogenase,5α-reductase 1
AMG-176	0					++++
VU661013	0					++++
BAI1	6						+
AZD5991	19					++++
MIK665 (S64315)	8					+++
S55746	2	+++
S63845	110					++++
BH3I-1	0				+				+	p53/MDM2
BDA-366	1	+++
A-1331852	59				++++ ++++				++++ ++++
A-1155463 Dihydrochloride	40				++++ ++++				++++ ++++
A-1210477	49					+++
UMI-77	21					++
WEHI-539	9				++++ ++++				++++ ++++
Gambogic Acid	3	+	+	+++	+ +	+		+	+ +	Caspase
Sonrotoclax	0	✔
Valepotriate	0	✔
Zeaxanthin	0	✔
Humanin	0	✔
Obatoclax (GX15-070)	6	✔
TCPOBOP	0	✔
Berberine chloride hydrate	2	✔								cytochrome c,PARP,Caspase 8
Nicotiflorin (Kaempferol-3-O-rutinoside)	0						✔			caspase-3,p-STAT3,p-JAK2
Nodakenetin	0						✔			BChE,AChE,RLAR
Cinobufagin	0	✔								PI3K,cyclin B,CDK1
Motixafortide (BL-8040)	0	✔								cyclin-D1,ERK,CXCR4
DT2216	0				✔				✔
Flavokawain A	0				✔				✔	XIAP,Survivin
Marinopyrrole A (Maritoclax)	4					✔
Berberine chloride	10	✔								PARP,Caspase-8,Topo II

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
LS147T	Growth Inhibition Assay	100 μM	72 h	IC50=29.5 μM	25208882
CX-1	Growth Inhibition Assay	100 μM	72 h	IC50=6.7 μM	25208882
PEER	Growth Inhibition Assay	10 μM	48 h	IC50=4.6403 μM	25301704
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

Re-engineered version of ABT-263 (Navitoclax).

Targets

Bcl-2 ^[1]
(Cell-free assay)

<0.01 nM(Ki)

In Vitro
In vitro	ABT-199 shows less sensitivity to Bcl-xL, Mcl-1 and Bcl-w with K_i of 48 nM, > 444 nM and 245 nM, respectively. ABT-199 potently inhibits FL5.12-Bcl-2 cells, RS4;11 cells with EC50 of 4 nM and 8 nM, while shows low activity against FL5.12-Bcl-xL cells with EC50 of 261 nM. ABT-199 induces a rapid apoptosis in RS4;11 cells with cytochrome c release, caspase activation, the externalization of phosphatidylserine and the accumulation of sub-G0/G1 DNA. Quantitative immunoblotting reveals that sensitivity to ABT-199 correlated strongly with the expression of Bcl-2, including NHL, DLBCL, MCL, AML and ALL cell lines. ABT-199 also induces apoptosis in CLL with an average EC50 of 3.0 nM. ^[1]
Kinase Assay	Binding affinity assays
Kinase Assay	Binding affinities (K_i or IC50) of ABT-199 against different isoforms of Bcl-2 family are determined with competitive fluorescence polarization assays. The following peptide probe/protein pairs are used: f-bad (1 nM) and Bcl-xL (6 nM), f-Bax (1 nM) and Bcl-2 (10 nM), f-Bax (1 nM) and Bcl-w (40 nM), f-Noxa (2 nM) and Mcl-1 (40 nM), and f-Bax (1 nM) and Bcl-2-A1 (15 nM). Binding affinities for Bcl-xL are also determined using a time-resolved fluorescence resonance energy transfer assay. Bcl-xL (1 nM, His tagged) is mixed with 200 nM f-Bak, 1 nM Tb-labeled anti-His antibody, and ABT-199 at room temperature for 30 min. Fluorescence is measured on an Envision plate reader using a 340/35 nm excitation filter and 520/525 (f-Bak) and 495/510 nm (Tb-labeled anti-His antibody) emission filters.
細胞実験	細胞株	NHL, DLBCL, MCL, AML and ALL cell lines
	濃度	~1 μM
	反応時間	48 hours
	実験の流れ	RS4;11 cells are seeded at 5 × 10⁴ per well in 96-well plates and treated with ABT-199 diluted in half-log steps starting at 1 μM-0.05 nM. Leukemia and lymphoma cell lines are seeded at 1.5-2 × 10⁴ cells per well in the appropriate medium and incubated with ABT-199 for 48 h. Effects on proliferation are determined using Cell TiterGlo reagent. EC50 values are determined by nonlinear regression analysis of the concentration-response data.
実験結果図	Methods	Biomarkers	結果図	PMID
	Western blot	Mcl-1 / Bcl-xl / Bcl-2 / Bak / NOXA / Bim PARP / Cleaved PARP / Caspase 3 / Cleaved caspase3 / p-S6(Ser236/236)		30663221
	Growth inhibition assay	Cell death Cell viability		28714472
	Immunofluorescence	Bcl-2 / Mcl-1		28767232

In Vivo
In Vivo	ABT-199 (100 mg/kg) causes a maximal tumor growth inhibition of 95% and tumor growth delay of 152% in RS4;11 xenografts. ABT-199 also inhibits xenograft growth (DoHH2, Granta-519) as a single agent or in combination with SDX-105 and other agents. ^[1]
動物実験	動物モデル	Female C.B-17 SCID mice (DoHH2 and Granta-519 xenografts) and female C.B-17 SCID-beige mice (RS4;11 and Toledo xenografts)
	投与量	~100 mg/kg
	投与経路	Orally

NCT Number	Recruitment	Conditions	Sponsor/Collaborators	Start Date	Phases
臨床試験 (data from https://clinicaltrials.gov, updated on 2024-05-22)
NCT06382168	Not yet recruiting	Leukemia Myeloid Acute	Delta-Fly Pharma Inc.	May 31 2024	Phase 1\|Phase 2
NCT06263387	Not yet recruiting	AML Adult	French Innovative Leukemia Organisation\|Acute Leukemia French Association	April 29 2024	--

参考
[1] Souers AJ, et al. Nat Med, 2013, 19(2), 202-208.

参考

[1] Souers AJ, et al. Nat Med, 2013, 19(2), 202-208.

化学情報

分子量	868.44	化学式	C₄₅H₅₀ClN₇O₇S
CAS No.	1257044-40-8	SDF	Download Venetoclax (ABT-199) SDFをダウンロードする
Smiles	CC1(CCC(=C(C1)C2=CC=C(C=C2)Cl)CN3CCN(CC3)C4=CC(=C(C=C4)C(=O)NS(=O)(=O)C5=CC(=C(C=C5)NCC6CCOCC6)[N+](=O)[O-])OC7=CN=C8C(=C7)C=CN8)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ケ月-20°Cin solvent

In vitro
Batch:

DMSO : 100 mg/mL ( (115.14 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	1.8mg/ml (2.07mM)	Taking the 1 mL working solution as an example, add 100 μL of 18 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	5%DMSO 1 Corn oil	2.5mg/ml (2.88mM)	Taking the 1 mL working solution as an example, add 50 μL of 50 mg/ml clear DMSO stock solution to 950 μL of corn oil and mix evenly. The mixed solution should be used immediately for optimal results.
Clear solution	5%DMSO 1 50%PEG300 Click to order 2 5%Tween 80 Click to order 3 40%ddH2O	2.5mg/ml (2.88mM)	Taking the 1 mL working solution as an example, add 50 μL of 50 mg/ml clarified DMSO stock solution to 500 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 400 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。

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よくある質問（FAQ）

質問1:
Could you please offer some advice on the half-life of the drug ?

回答
According to the reference (https://www.ncbi.nlm.nih.gov/pubmed/24212376), the half-life of ABT-199 in dogs is 12.9 hr.

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