Venetoclax (ABT-199, GDC-0199)
Catalog No.S8048
Molecular Weight(MW): 868.44
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. Phase 3.
Purity & Quality Control
Choose Selective Bcl-2 Inhibitors
Biological Activity
| Description | 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. Phase 3. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Features | Re-engineered version of ABT-263 (Navitoclax). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Targets |
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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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| Cell Data |
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| Assay |
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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] |
Protocol
| Kinase Assay:[1] |
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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 Research:[1] |
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| Animal Research:[1] |
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Solubility (25°C)
| In vitro | DMSO | 100 mg/mL warmed (115.14 mM) |
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| Water | Insoluble | |
| Ethanol | Insoluble | |
| In vivo | Add solvents to the product individually and in order(Data is from Selleck tests instead of citations): 5% DMSO+50% PEG 300+5% Tween 80+ddH2O For best results, use promptly after mixing. |
5mg/mL |
* 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 Information
| Molecular Weight | 868.44 |
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| Formula | C45H50ClN7O7S |
| CAS No. | 1257044-40-8 |
| Storage | powder |
| in solvent | |
| Synonyms | N/A |
Bio Calculators
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Clinical Trial Information
| NCT Number | Recruitment | Conditions | Sponsor/Collaborators | Start Date | Phases |
|---|---|---|---|---|---|
| NCT03872180 | Not yet recruiting | CCND1 Positive|Mantle Cell Lymphoma|t(11;14) Positive | Emory University|Genentech Inc. | March 1 2020 | Phase 2 |
| NCT03872180 | Not yet recruiting | CCND1 Positive|Mantle Cell Lymphoma|t(11;14) Positive | Emory University|Genentech Inc. | March 1 2020 | Phase 2 |
| NCT03884972 | Not yet recruiting | Refractory Chronic Lymphocytic Leukemia|Refractory Small Lymphocytic Lymphoma | M.D. Anderson Cancer Center|National Cancer Institute (NCI) | December 1 2019 | Phase 1 |
| NCT03884972 | Not yet recruiting | Refractory Chronic Lymphocytic Leukemia|Refractory Small Lymphocytic Lymphoma | M.D. Anderson Cancer Center|National Cancer Institute (NCI) | December 1 2019 | Phase 1 |
| NCT03868722 | Not yet recruiting | CLL | Rigshospitalet Denmark|Stichting Hemato-Oncologie voor Volwassenen Nederland|Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)|Karolinska Institutet | August 1 2019 | Phase 2|Phase 3 |
| NCT03868722 | Not yet recruiting | CLL | Rigshospitalet Denmark|Stichting Hemato-Oncologie voor Volwassenen Nederland|Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)|Karolinska Institutet | August 1 2019 | Phase 2|Phase 3 |
Tech Support
Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.
Tel: +1-832-582-8158 Ext:3
If you have any other enquiries, please leave a message.
Frequently Asked Questions
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Question 1:
Could you please offer some advice on the half-life of the drug ?
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Answer:
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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Question 2:
how to prepare the working solution for mice including how to dissolve the powder?
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Answer:
We recommend the following vehicle for ABT 199, 30% PEG400/0.5% Tween80/5% Propylene glycol (64.5% water, V/V), at a concentration up to 20mg/ml. Its a homogeneous suspension and can be used for oral gavage.
