Venetoclax (ABT-199)

製品コードS8048 バッチS804814

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 100 mg/mL (115.14 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) 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.
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]
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]
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 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 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.
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

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：

RAS-mutant leukaemia stem cells drive clinical resistance to venetoclax [ Nature, 2024, ] PubMed: 39478230
Dual blockade of IL-10 and PD-1 leads to control of SIV viral rebound following analytical treatment interruption [ Nat Immunol, 2024, 10.1038/s41590-024-01952-4] PubMed: 39266691
Proteasome inhibition enhances the anti-leukemic efficacy of chimeric antigen receptor (CAR) expressing NK cells against acute myeloid leukemia [ J Hematol Oncol, 2024, 17(1):85] PubMed: 39285441
Comprehensive characterization of IFNγ signaling in acute myeloid leukemia reveals prognostic and therapeutic strategies [ Nat Commun, 2024, 15(1):1821] PubMed: 38418901
AXL-specific single domain antibodies show diagnostic potential and anti-tumor activity in Acute Myeloid Leukemia [ Theranostics, 2024, 14(7):2656-2674] PubMed: 38773967
AXL-specific single domain antibodies show diagnostic potential and anti-tumor activity in Acute Myeloid Leukemia [ Theranostics, 2024, 14(7):2656-2674] PubMed: 38773967
BH3 mimetics and azacitidine show synergistic effects on juvenile myelomonocytic leukemia [ Leukemia, 2024, 38(1):136-148] PubMed: 37945692
8-Cl-Ado and 8-NH2-Ado synergize with venetoclax to target the methionine-MAT2A-SAM axis in acute myeloid leukemia [ Leukemia, 2024, 10.1038/s41375-024-02222-w] PubMed: 38643304
Targeting BCL2 with Venetoclax Enhances the Efficacy of the KRASG12D Inhibitor MRTX1133 in Pancreatic Cancer [ Cancer Res, 2024, 10.1158/0008-5472.CAN-23-3574] PubMed: 39137400
Dual ON/OFF-switch chimeric antigen receptor controlled by two clinically approved drugs [ Proc Natl Acad Sci U S A, 2024, 121(44):e2405085121] PubMed: 39453747

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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