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

文献中Selleckの製品使用例（618）

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)と併用されることが多い化合物

A-1210477

This compound and A-1210477 increase MCL1 expression and synergistically induce apoptosis in acute myeloid leukemia (AML) cells, MOLM13/MV4-11/SKM1/OCI-AML5.

Navitoclax (ABT-263)

It, Navitoclax and chemotherapy show promising efficacy and tolerability in patients with relapsed/refractory acute lymphoblastic leukemia.

S63845

It and S63845 significantly delay the time to viral rebound by 4-fold after antiretroviral therapy (ART) cessation in a humanized mouse model of HIV-1 infection.

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

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
KARPAS-45	Growth Inhibition Assay	10 μM	48 h	IC50=3.2225 μM	25301704
PF-382	Growth Inhibition Assay	10 μM	48 h	IC50=2.1824 μM	25301704
DND-41	Growth Inhibition Assay	10 μM	48 h	IC50=1.9695 μM	25301704
KOPTK1	Growth Inhibition Assay	10 μM	48 h	IC50=0.6432 μM	25301704
CUTLL1	Growth Inhibition Assay	10 μM	48 h	IC50=0.3823 μM	25301704
ALL-SIL	Growth Inhibition Assay	10 μM	48 h	IC50=0.1803 μM	25301704
LOUCY	Growth Inhibition Assay	10 μM	48 h	IC50=0.0139 μM	25301704
KCL22	Function Assay	2 μM	48 h	Increases DNA fragamentation	25333252
SU-DHL-6	Function Assay	0.75 μM	18 h	Increases pro-survival protein MCL-1 expression	25590803
CS-THL1	Growth Inhibition Assay	20 nM	72 h	Inhibits cell growth assessed by cell viability	25916698
MOLM-13	Apoptotic Assay	50 nM	24 h	Apoptosis induction	24346116
HSB	Growth Inhibition Assay	10 μM	48 h	IC50=4.448 μM	24342948
MOLT4	Growth Inhibition Assay	10 μM	48 h	IC50=4.154 μM	24342948
SKW-3/KE-37	Growth Inhibition Assay	10 μM	48 h	IC50=0.712 μM	24342948
SUPT-11	Growth Inhibition Assay	10 μM	48 h	IC50=4.473 μM	24342948
JURKAT	Growth Inhibition Assay	10 μM	48 h	IC50=4.893 μM	24342948
CCRF-CEM	Growth Inhibition Assay	10 μM	48 h	IC50=1.360 μM	24342948
LOUCY	Apoptotic Assay	2 μM	48 h	Apoptosis induction	24342948
OCI-Ly19	Growth Inhibition Assay	1 μM		Inhibits cell growth assessed by cell viability	25590803
SU-DHL-6	Growth Inhibition Assay	0.8 μM		Inhibits cell growth assessed by cell viability	25590803
DoGKiT	Apoptotic Assay	50 nM		Induces apoptosis	25916698
CS-THL1	Apoptotic Assay	25 nM		Induces apoptosis	25916698
NALM-6	Growth Inhibition Assay		72 h	IC50>3 μM	25649768
RS4-11	Growth Inhibition Assay		72 h	IC50=0.0402 μM	25649768
HL-60	Growth Inhibition Assay		48 h	IC50<1 μM	24346116
MOLM-13	Growth Inhibition Assay		48 h	IC50<1 μM	24346116
OCI-AML2	Growth Inhibition Assay		48 h	IC50<1 μM	24346116
Kasumi-1	Growth Inhibition Assay		48 h	IC50<1 μM	24346116
KG-1	Growth Inhibition Assay		48 h	IC50<1 μM	24346116
THP-1	Growth Inhibition Assay		48 h	IC50<1 μM	24346116
MOLM-14	Growth Inhibition Assay		48 h	IC50<1 μM	24346116
RS4:11	MTS assay		72 h		30278333
Toledo	MTS assay		72 h		30278333
NCI60	SRB assay		48 h		27994761
RS4:11	MTT assay		24 h		29453135
melanoma	SRB assay		48 h		27994761
leukemia	SRB assay		48 h		27994761
renal cancer	SRB assay		48 h		27994761
non-small cell lung cancer	SRB assay		48 h		27994761
breast cancer	SRB assay		48 h		27994761
colon cancer	SRB assay		48 h		27994761
ovarian cancer	SRB assay		48 h		27994761
CNS cancer	SRB assay		48 h		27994761
prostate cancer	SRB assay		48 h		27994761
Remb1	MTT assay		24 h		29453135
RS4:11	Cytotoxicity assay				29407973
RS4:11	MTS assay				28926247
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	Venetoclax (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. It 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. This compound 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 it correlated strongly with the expression of Bcl-2, including NHL, DLBCL, MCL, AML and ALL cell lines. It 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 Venetoclax (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). Its 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 this compound 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	Venetoclax (ABT-199) is diluted in half-log steps starting at 1 μM-0.05 nM and used to treat RS4;11 cells seeded at 5 × 10⁴ per well in 96-well plates. Leukemia and lymphoma cell lines are seeded at 1.5-2 × 10⁴ cells per well in the appropriate medium and incubated with this compound 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	Venetoclax (ABT-199) causes a maximal tumor growth inhibition of 95% and tumor growth delay of 152% in RS4;11 xenografts. It 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
https://pubmed.ncbi.nlm.nih.gov/23291630/

参考

https://pubmed.ncbi.nlm.nih.gov/23291630/

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
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Clear solution	5%DMSO 1 Corn oil この製剤はselleckのラボで検証済みです。上記の溶解方法がご要望を満たさない場合、selleckの営業担当までお問い合わせ頂ければ、個別の試験を行います。	2.500mg/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	10% DMSO 1 40% PEG 300 2 5%Tween80 3 45%ddH2O この製剤はselleckのラボで検証済みです。上記の溶解方法がご要望を満たさない場合、selleckの営業担当までお問い合わせ頂ければ、個別の試験を行います。	1.800mg/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.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Clear solution	5%DMSO 1 50%PEG300 2 5%Tween80 3 40%ddH2O この製剤はselleckのラボで検証済みです。上記の溶解方法がご要望を満たさない場合、selleckの営業担当までお問い合わせ頂ければ、個別の試験を行います。	2.500mg/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.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.

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.

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):