Venetoclax (ABT-199)

別名:GDC-0199

Venetoclax (ABT-199, GDC-0199) is a Bcl-2-selective inhibitor with Ki 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.

Venetoclax (ABT-199)化学構造

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
JPY 40500 国内在庫あり
JPY 145500 国内在庫あり
JPY 295500 国内在庫あり

代表番号: 045-509-1970|電子メール:[email protected]
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製品安全説明書

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Venetoclax (ABT-199)と併用されることが多い化合物

A-1331852


Venetoclax and A-1331852, when used in combination with nilotinib, synergistically reduce cell viability, and enhance apoptosis in blast phase-chronic myeloid leukemia cell lines.


Parry N, et al. Cell Death Discov. 2022 Nov 15;8(1):457.

Azacitidine (5-Azacytidine)


Combining Venetoclax and Azacitidine targets leukemia stem cells and disrupts abnormal energy metabolism in AML patients with poor outcomes.


Pollyea DA, et al.Nat Med. 2018 Dec;24(12):1859-1866.

A-1210477


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


Fiskus W, et al. Blood Cancer J. 2019 Jan 15;9(2):4.

Navitoclax (ABT-263)


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


Pullarkat VA, et al. Cancer Discov. 2021 Jun;11(6):1440-1453.

S63845


Venetoclax 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.


Arandjelovic P, et al. Cell Rep Med. 2023 Aug 23;101178.

Venetoclax (ABT-199)関連製品

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
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生物活性

製品説明 Venetoclax (ABT-199, GDC-0199) is a Bcl-2-selective inhibitor with Ki 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.
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 Ki 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
Binding affinities (Ki 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
NCT05668026 Not yet recruiting
HIV-1-infection
University of Aarhus|The Peter Doherty Institute for Infection and Immunity|Walter and Eliza Hall Institute of Medical Research|The Alfred|Aarhus University Hospital
March 1 2024 Phase 1|Phase 2
NCT06191263 Not yet recruiting
Acute Myeloid Leukemia
Ryvu Therapeutics SA
January 2024 Phase 2
NCT06014489 Not yet recruiting
AML Adult
Stichting Hemato-Oncologie voor Volwassenen Nederland
December 2023 Phase 2

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

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

実験計算

モル濃度計算器

質量 濃度 体積 分子量

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)

mg/kg g μL

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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