| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| 10mg |
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| 50mg |
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| 100mg |
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| Other Sizes |
| Targets |
Desmorpholinyl Navitoclax-NH-Me targets Bcl-xL, a member of the BCL-2 family of anti-apoptotic proteins. Bcl-xL is overexpressed in various cancers and promotes cell survival by inhibiting apoptosis. Inhibition of Bcl-xL by this compound promotes apoptosis in cancer cells. The compound is designed for use in PROTAC technology, where it is conjugated to a CRBN ligand to form a heterobifunctional molecule that induces degradation of BCL-XL protein. This dual mechanism provides a powerful approach for cancer therapy.
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| ln Vitro |
Desmorpholinyl Navitoclax-NH-Me demonstrates in vitro activity as a Bcl-xL inhibitor. It is used in the synthesis of PROTAC BCL-XL degrader XZ739, which induces degradation of BCL-XL protein. The compound facilitates the study of apoptosis regulation in various cancer cell lines. As a potent inhibitor of BCL-2 family proteins, it promotes apoptosis in cancer cells. Detailed IC50 values and degradation efficacy data are available in the primary literature.
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| ln Vivo |
In vivo studies for Desmorpholinyl Navitoclax-NH-Me are typically conducted on the PROTAC BCL-XL degrader XZ739 synthesized using this compound. XZ739 is evaluated in animal models for its ability to degrade BCL-XL and inhibit tumor growth. The PROTAC approach offers advantages over traditional inhibition by inducing protein degradation rather than just inhibition. Studies in appropriate cancer models would evaluate the in vivo efficacy, pharmacokinetics, and safety of the PROTAC degrader.
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| Enzyme Assay |
For Bcl-xL binding assays, purified Bcl-xL protein is incubated with Desmorpholinyl Navitoclax-NH-Me at various concentrations. Binding affinity is measured by surface plasmon resonance, isothermal titration calorimetry, or fluorescence polarization using labeled probes. For PROTAC synthesis, the compound is conjugated to a CRBN ligand through appropriate chemistry. The resulting PROTAC is purified and characterized by mass spectrometry and HPLC. For degradation assays, cells are treated with the PROTAC and BCL-XL protein levels are assessed by Western blot.
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| Cell Assay |
For cellular activity studies, cancer cell lines expressing Bcl-xL are cultured in appropriate media. Cells are treated with Desmorpholinyl Navitoclax-NH-Me or the PROTAC XZ739 at various concentrations for 24-72 hours. Cell viability is assessed using MTT or CellTiter-Glo assays, and IC50 values are calculated. Apoptosis induction is evaluated by Annexin V-FITC/PI staining and flow cytometry, or by caspase-3/7 activity assays. For PROTAC studies, BCL-XL degradation is assessed by Western blot using specific antibodies.
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| Animal Protocol |
For in vivo efficacy studies, immunodeficient mice bearing tumor xenografts expressing Bcl-xL are administered the PROTAC XZ739 (containing Desmorpholinyl Navitoclax-NH-Me as the warhead) via intravenous or intraperitoneal injection. Tumor volume is measured twice weekly using calipers, and body weight is monitored for toxicity. At study termination, tumors are collected for Western blot analysis to confirm BCL-XL degradation and assessment of apoptosis markers.
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| ADME/Pharmacokinetics |
Pharmacokinetic properties of Desmorpholinyl Navitoclax-NH-Me are characterized as part of the PROTAC XZ739. The compound has a molecular weight of 918.55 and is a large molecule. As a PROTAC component, it is designed to achieve therapeutic concentrations in tumor tissues. Detailed PK parameters depend on the specific formulation and administration route. The compound is typically stored according to manufacturer recommendations.
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| Toxicity/Toxicokinetics |
Desmorpholinyl Navitoclax-NH-Me is a research compound intended for laboratory use only and is not approved for human therapeutic use. As a Bcl-xL inhibitor, it is used in the synthesis of PROTAC BCL-XL degrader XZ739. The compound facilitates the study of apoptosis regulation in cancer cells. Standard laboratory safety precautions should be followed when handling this compound.
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| References | |
| Additional Infomation |
Desmorpholinyl Navitoclax-NH-Me is a Bcl-xL inhibitor with molecular formula C44H51ClF3N5O5S3 and molecular weight 918.55. It is used with a CRBN ligand to synthesize PROTAC BCL-XL degrader XZ739. The compound is used in cancer research to study apoptosis regulation and BCL-2 family protein inhibition. It is for research use only and has not been approved for clinical applications.
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| Molecular Formula |
C44H51CLF3N5O5S3
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|---|---|
| Molecular Weight |
918.549456834793
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| Exact Mass |
917.269
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| CAS # |
2365172-82-1
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| PubChem CID |
139331525
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| Appearance |
White to off-white solid powder
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| LogP |
9.5
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
13
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| Rotatable Bond Count |
16
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| Heavy Atom Count |
61
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| Complexity |
1680
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| Defined Atom Stereocenter Count |
1
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| SMILES |
ClC1C=CC(=CC=1)C1CCC(C)(C)CC=1CN1CCN(C2C=CC(C(NS(C3C=CC(=C(C=3)S(C(F)(F)F)(=O)=O)N[C@@H](CSC3C=CC=CC=3)CCNC)(=O)=O)=O)=CC=2)CC1
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| InChi Key |
CNTHZPROCQHGOX-PGUFJCEWSA-N
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| InChi Code |
InChI=1S/C44H51ClF3N5O5S3/c1-43(2)21-19-39(31-9-13-34(45)14-10-31)33(28-43)29-52-23-25-53(26-24-52)36-15-11-32(12-16-36)42(54)51-61(57,58)38-17-18-40(41(27-38)60(55,56)44(46,47)48)50-35(20-22-49-3)30-59-37-7-5-4-6-8-37/h4-18,27,35,49-50H,19-26,28-30H2,1-3H3,(H,51,54)/t35-/m1/s1
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| Chemical Name |
4-[4-[[2-(4-chlorophenyl)-5,5-dimethylcyclohexen-1-yl]methyl]piperazin-1-yl]-N-[4-[[(2R)-4-(methylamino)-1-phenylsulfanylbutan-2-yl]amino]-3-(trifluoromethylsulfonyl)phenyl]sulfonylbenzamide
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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)
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| Solubility (In Vitro) |
DMSO : 100 mg/mL (108.87 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: 2.5 mg/mL (2.72 mM) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), suspension solution; with sonication.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: 2.5 mg/mL (2.72 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.5 mg/mL (2.72 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.0887 mL | 5.4434 mL | 10.8867 mL | |
| 5 mM | 0.2177 mL | 1.0887 mL | 2.1773 mL | |
| 10 mM | 0.1089 mL | 0.5443 mL | 1.0887 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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