ABT-199 (Venetoclax)

製品コードS8048 バッチS804821

印刷

化学情報

Chemical Structure Synonyms GDC-0199 Storage
(From the date of receipt)		 3 years -20°C powder
1 years -80°C in solvent
化学式

C45H50ClN7O7S
分子量 868.44 CAS No. 1257044-40-8
Solubility (25°C)* 体外 DMSO 250 mg/mL (287.87 mM)
Water Insoluble
Ethanol Insoluble
* <1 mg/ml means slightly soluble or insoluble.
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.

溶剤液（一定の濃度）を調合する

生物活性

製品説明 Venetoclax (ABT-199, GDC-0199) は、無細胞アッセイにおいてKiが<0.01 nMであるBcl-2選択的阻害剤であり、Bcl-xLおよびBcl-wに対しては4800倍以上選択性が高く、Mcl-1に対しては活性を示しません。Venetoclaxは、トリプルネガティブ乳癌MDA-MB-231細胞において、細胞増殖抑制、アポトーシス、細胞周期停止、およびオートファジーを誘導すると報告されています。フェーズ3。
in vitro Venetoclax (ABT-199) shows less sensitivity to Bcl-xL, Mcl-1 and Bcl-w with Ki 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.
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.
特徴 Re-engineered version of ABT-263 (Navitoclax).

プロトコル(参考用のみ)

キナーゼアッセイ Binding affinity assays
Binding affinities (Ki 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. In this assay, Bcl-xL (1 nM, His tagged) is mixed with 200 nM f-Bak, 1 nM Tb-labeled anti-His antibody, and the 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.
細胞アッセイ 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 Venetoclax (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 it 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.
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)
投薬量 ~100 mg/kg
投与方法 Orally

参考

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

カスタマーフィードバック

Data from [Data independently produced by Mol Oncol, 2014, 10.1016/j.molonc.2014.09.008]

Data from [J Biol Chem, 2014, 289(23), 16190-9]

Data from [Data independently produced by , , Blood, 2015, 126(11):1346-56]

Selleckの高級品が、幾つかの出版された研究調査結果（以下を含む）で使われた：

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Oncogenic role of RARG rearrangements in acute myeloid leukemia resembling acute promyelocytic leukemia [ Nat Commun, 2025, 16(1):617] PubMed: 39805831

長期の保管のために-20°Cの下で製品を保ってください。

人間や獣医の診断であるか治療的な使用のためにでない。

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