- 貨號 Cat. No.
- S8048
- 規格 Size
- 5~200mg
- 品牌 Brand
- Selleckchem
Description
ABT-199 (GDC-0199)
Catalog No.S8048
ABT-199 (GDC-0199) is a Bcl-2-selective inhibitor with Ki of <0.01 nM, >4800-fold more selective versus Bcl-xL and Bcl-w, and no activity to Mcl-1. Phase 2.
Size |
Price |
Stock |
Quantity |
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10mM/1mLIn DMSO |
USD 856 |
In stock |
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10
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5mg |
USD 340 |
In stock |
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10
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50mg |
USD 1222 |
In stock |
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10
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Distributor Tel: +886-2-2827-1197jimmy@new.abscience.com.tw
Biological Activity
Description |
ABT-199 (GDC-0199) is a Bcl-2-selective inhibitor with Ki of <0.01 nM, >4800-fold more selective versus Bcl-xL and Bcl-w, and no activity to Mcl-1. Phase 2. |
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Targets |
Bcl-2 |
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IC50 |
< 0.010 nM (Ki) [1] |
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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] |
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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] |
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Features |
Re-engineered version of ABT-263 (Navitoclax). |
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Protocol(Only for Reference)
Kinase Assay: [1]
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. |
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Cell Assay: [1]
Cell lines |
NHL, DLBCL, MCL, AML and ALL cell lines |
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Concentrations |
~1 μM |
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Incubation Time |
48 hours |
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Method |
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. |
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Animal Study: [1]
Animal Models |
Female C.B-17 SCID mice (DoHH2 and Granta-519 xenografts) and female C.B-17 SCID-beige mice (RS4;11 and Toledo xenografts) |
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Dosages |
~100 mg/kg |
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Administration |
Orally |
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Solubility |
30% PEG400/0.5% Tween80/5% propylene glycol, 20 mg/mL |
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1
References
Clinical Trial Information( data from http://clinicaltrials.gov)
NCT Number |
Recruitment |
Conditions |
Sponsor
/Collaborators |
Start Date |
Phases |
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NCT01794520 |
Recruiting |
Relapsed/Refractory Multiple Myeloma |
AbbVie|AbbVie (prior sponsor, Abbott)|Genentech |
2012-10 |
Phase 1 |
NCT01685892 |
Suspended |
Lymphocytic Leukemia, Chronic |
Genentech |
2012-11 |
Phase 1 |
NCT01686555 |
Recruiting |
Systemic Lupus Erythematosus |
AbbVie|AbbVie (prior sponsor, Abbott) |
2012-11 |
Phase 1 |
NCT01794507 |
Recruiting |
Relapsed/Refractory Multiple Myeloma |
AbbVie|AbbVie (prior sponsor, Abbott)|Genentech |
2012-11 |
Phase 1 |
NCT01671904 |
Suspended |
Lymphocytic Leukemia, Chronic |
Genentech|AbbVie (prior sponsor, Abbott) |
2013-05 |
Phase 1 |
Molecular Weight (MW) |
868.44 |
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Formula |
C45H50ClN7O7S
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CAS No. |
1257044-40-8 |
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Storage |
3 years -20℃Powder |
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6 months-80℃in DMSO |
Syonnyms |
N/A |
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Solubility (25°C) * |
In vitro |
DMSO |
100 mg/mL (115 mM) |
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Water |
<1 mg/mL (<1 mM) |
Ethanol |
<1 mg/mL (<1 mM) |
In vivo |
30% PEG400/0.5% Tween80/5% propylene glycol, |
20 mg/mL |
* <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. |
Chemical Name |
Benzamide, 4-[4-[[2-(4-chlorophenyl)-4,4-dimethyl-1-cyclohexen-1-yl]methyl]-1-piperazinyl]-N-[[3-nitro-4-[[(tetrahydro-2H-pyran-4-yl)methyl]amino]phenyl]sulfonyl]-2-(1H-pyrrolo[2,3-b]pyridin-5-yloxy)- |
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Stock Solution (1ml DMSO) |
1mM |
10mM |
20mM |
30mM |
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Mass(mg) |
0.86844 |
8.6844 |
17.3688 |
26.0532 |
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