| 包装 | 价格(元) |
| 10mM (in 1mL DMSO) | 电议 |
| 2mg | 电议 |
| 5mg | 电议 |
| 10mg | 电议 |
| 50mg | 电议 |
| 100mg | 电议 |
Preparation Method | The affinity of ABT-199 for different subtypes of the Bcl-2 family (Ki or IC50) was determined by competitive fluorescence polarization assays using the following peptide probe/protein pairs: 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 the affinity of F-Bax (1 nM) and Bcl-2-A1(15 nM) for Bcl-XL was determined by time-resolved fluorescence resonance energy transfer assays.1 nM Tb labeled anti-His antibody,And ABT-199 were mixed for 30 min at room temperature on Envision microplate reader. Fluorescence values were measured using excitation filters at 340/35 nm and emission filters at 520/525 (F-BAK) and 495/510 nm (anti-His antibody labeled with Tb). |
Reaction Conditions | ABT-199 with Bcl-2 for 30 min at RT |
Applications | ABT-199 has a subnanomolar affinity for BCL-2 (Ki< 0.010 nM) and bound over three orders of magnitude less avidly to BCL-XL (Ki = 48 nM) and BCL-W (Ki = 245 nM) than to BCL-2. |
Cell lines | NHL cell lines |
Preparation Method | The viability of NHL cell lines was examined after 48 h incubation with increasing concentrations of Navitoclax or ABT-199. |
Reaction Conditions | 0.01 μM -3.0 μM ABT-199 for 48h |
Applications | ABT-199 cell killing was selective and mechanism dependent, BCL2high status is thus a potential predictive marker for sensitivity to ABT-199. |
Animal models | Female C.B-17 SCID-beige mice |
Preparation Method | All xenograft trials were conducted using ten mice per group, and all mice were ear tagged and monitored individually throughout the studies. ABT-199 was formulated for oral dosing in 60% phosal 50 propylene glycol (PG), 30% polyethylene glycol (PEG) 400 and 10% ethanol. ABT-199 was delivered approximately 2 h before bendamustine or bendamustine plus rituximab. |
Dosage form | 12.5 mg/kg ABT-199 for 60 days |
Applications | After a single oral dose of 12.5 mg per kg body weight in xenografts derived from RS4;11 cells (ALL), ABT-199 caused a maximal tumor growth inhibition (TGImax) of 47% and tumor growth delay (TGD) of 26%. |
| 文献引用 | |
| 产品描述 | Venetoclax (ABT-199, GDC-0199) is a selective inhibitor of Bcl-2 with a K i of 0.01 nM in cell-free assays. Compared to Bcl-XL and Bcl-W more than 4800 times more selective, no inhibitory activity against McL-1[1]. ABT-199 cell killing was selective and mechanism dependent, BCL2high status is thus a potential predictive marker for sensitivity to ABT-199[1].BIM binding to BCL2 correlates with ABT-199 response and further showed that knockout of BIM results in decreased ABT-199 sensitivity. Eexpression of B-cell genes as enriched in ABT-199-sensitive myeloma, although no single gene consistently delineated sensitive and resistant cells[4]. In the ABT-199-resistant OCI-AML3 cell line, CXCL12 promoted an increase in the proportion of cells expressing high levels of embryonic stem cell core transcription factors abrogated by CD44 knockdown[7].The T-ALL cell line LOUCY, which shows a transcriptional program related to immature T-ALL, exhibited high in vitro and in vivo sensitivity for ABT-199 in correspondence with high levels of BCL-2. In addition, ABT-199 showed synergistic therapeutic effects with different chemotherapeutic agents[3].When performed a genome-wide CRISPR knockout screen and found that inactivation of genes involved in mitochondrial translation restored sensitivity to ABT-199 in resistant AML cells. Pharmacologic inhibition of mitochondrial protein synthesis with antibiotics that target the ribosome, including tedizolid and doxycycline, effectively overcame ABT-199 resistance[6]. VU661013 is a novel, potent, selective MCL1 inhibitor. VU661013 was safely combined with ABT-199 for synergy in murine models of AML[3].ABT-199 and 5-Aza act synergistically to kill AML cells in vitro and display combinatorial antitumor activity in vivo[5]. Treatment with ABT-199 alone and in combination is well tolerated, with the most common side effects being neutropenia, infection, and gastrointestinal toxic effects[2]. References: |
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