| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
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| 5mg | |||
| Other Sizes |
| Targets |
Targets (as internal standard): Isotope-Labeled Compounds / Bcl-2 Family. The parent Venetoclax specifically inhibits the anti-apoptotic protein B-cell lymphoma 2 (Bcl-2) by binding to its BH3-binding groove, displacing pro-apoptotic proteins such as BIM, leading to mitochondrial outer membrane permeabilization and caspase-dependent apoptosis in Bcl-2-dependent cancer cells.
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|---|---|
| ln Vitro |
Drug compounds have included stable heavy isotopes of carbon, hydrogen, and other elements, mostly as quantitative tracers while the drugs were being developed. Because deuteration may have an effect on a drug's pharmacokinetics and metabolic properties, it is a cause for concern [1].
No direct in vitro activity is reported for the labeled standard. The parent compound Venetoclax exhibits potent in vitro activity against Bcl-2-dependent cell lines (e.g., RS4;11, with EC50 < 0.01 nM). It induces autophagy and apoptosis in a concentration-dependent manner in various hematological cancer cell lines. |
| ln Vivo |
In vivo, Venetoclax is orally active and has demonstrated significant anti-tumor efficacy in mouse xenograft models of acute lymphoblastic leukemia and non-Hodgkin lymphoma, resulting in tumor regression. The deuterated standard is an internal standard for these studies and is not itself administered.
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| Enzyme Assay |
For cell-free assays: plasma or tissue homogenate samples are spiked with the internal standard, followed by protein precipitation with acetonitrile or solid-phase extraction. The samples are injected onto an LC-MS/MS system, and quantitation is achieved by comparing the analyte peak area to the internal standard peak area.
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| Cell Assay |
No cell-based assays are performed with the deuterated standard. The parent Venetoclax is tested in cell viability assays using Bcl-2-dependent cell lines (e.g., RS4;11, NHL-1), incubated with the compound for 48-72 hours, and cell death is measured by CTG or Annexin V flow cytometry. Potency is expressed as EC50 or IC50 values.
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| Animal Protocol |
Animal studies for the deuterated standard are not applicable. In vivo PK studies of unlabeled Venetoclax involve oral or IV administration to mice, rats, or dogs, followed by serial blood collection. Plasma is processed with the internal standard and analyzed by LC-MS/MS to determine PK parameters such as Cmax, Tmax, t1/2, and AUC.
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| ADME/Pharmacokinetics |
PK properties of parent Venetoclax: oral bioavailability is high (approx. 70-80% in humans), with peak plasma concentrations (Tmax) achieved 2-4 hours post-dose. It is highly plasma protein bound (>99.9%), has a large volume of distribution (100-200 L), and a long terminal elimination half-life (approx. 17-26 hours in humans). The deuterated standard does not exhibit distinct PK behavior.
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| Toxicity/Toxicokinetics |
No toxicity data are reported for the deuterated standard. Parent Venetoclax has a well-characterized safety profile, including common adverse effects such as neutropenia, thrombocytopenia, anemia, diarrhea, nausea, and upper respiratory tract infection. Tumor lysis syndrome (TLS) is a serious but manageable risk. The labeled compound is for research use only.
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| References |
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| Additional Infomation |
Venetoclax-d8 is a research standard and not an active drug substance. It is used for quality control, impurity profiling, and analytical method validation in pharmaceutical manufacturing. Venetoclax is FDA-approved for chronic lymphocytic leukemia (CLL), small lymphocytic lymphoma (SLL), and acute myeloid leukemia (AML) in specific patient populations.
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| Molecular Formula |
C45H50CLN7O7S
|
|---|---|
| Molecular Weight |
868.439208507538
|
| Exact Mass |
875.368
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| CAS # |
1257051-06-1
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| Related CAS # |
Venetoclax;1257044-40-8
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| PubChem CID |
131971741
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| Appearance |
Light yellow to yellow solid powder
|
| LogP |
8.2
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
11
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| Rotatable Bond Count |
12
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| Heavy Atom Count |
61
|
| Complexity |
1640
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| Defined Atom Stereocenter Count |
0
|
| SMILES |
C(N1C([H])([H])C([H])([H])N(C2C=CC(C(=O)NS(C3C=CC(NCC4CCOCC4)=C(N(=O)=O)C=3)(=O)=O)=C(OC3=CN=C4NC=CC4=C3)C=2)C([H])([H])C1([H])[H])C1CCC(C)(C)CC=1C1C=CC(Cl)=CC=1
|
| InChi Key |
LQBVNQSMGBZMKD-JYSKPPGCSA-N
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| InChi Code |
InChI=1S/C45H50ClN7O7S/c1-45(2)15-11-33(39(26-45)31-3-5-34(46)6-4-31)29-51-17-19-52(20-18-51)35-7-9-38(42(24-35)60-36-23-32-12-16-47-43(32)49-28-36)44(54)50-61(57,58)37-8-10-40(41(25-37)53(55)56)48-27-30-13-21-59-22-14-30/h3-10,12,16,23-25,28,30,48H,11,13-15,17-22,26-27,29H2,1-2H3,(H,47,49)(H,50,54)/i17D2,18D2,19D2,20D2
|
| Chemical Name |
4-[4-[[2-(4-chlorophenyl)-4,4-dimethylcyclohexen-1-yl]methyl]-2,2,3,3,5,5,6,6-octadeuteriopiperazin-1-yl]-N-[3-nitro-4-(oxan-4-ylmethylamino)phenyl]sulfonyl-2-(1H-pyrrolo[2,3-b]pyridin-5-yloxy)benzamide
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
|
| Solubility (In Vitro) |
DMSO : ~125 mg/mL (~142.61 mM)
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|---|---|
| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.1515 mL | 5.7575 mL | 11.5149 mL | |
| 5 mM | 0.2303 mL | 1.1515 mL | 2.3030 mL | |
| 10 mM | 0.1151 mL | 0.5757 mL | 1.1515 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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