| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| 10mg |
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| Other Sizes |
| Targets |
Bcl-xL 2.5 nM (DC50) Cereblon
XZ739 targets BCL-XL (Bcl-2 family member) for degradation. It is a Cereblon-dependent PROTAC that recruits the CRBN E3 ubiquitin ligase to BCL-XL, leading to ubiquitination and proteasomal degradation. The compound induces cell death through caspase-mediated apoptosis. |
|---|---|
| ln Vitro |
After 48 hours of treatment with IC50s of 10.1, 41.8, 25.3, and 1217 nM, respectively, XZ739 (0.001-10 μM; 48 hours) significantly decreases platelets in T-ALL MOLT-4, B-ALL RS4, SCLC 11, and NCI-H146 cells. XZ739 has a selectivity for MOLT-4 cells that is more than 100 times higher than human platelets [1]. BCL-XL degradation is induced in MOLT-4 cells by XZ739 (1.2-300 nM; 16 hours) [1]. Within two hours of XZ739 treatment, MOLT-4 exhibits rapid BCL-XL degradation driven by XZ739; eight hours later, 100 nM XZ739 had degraded over 96% of BCL-XL [1]. After a 48-hour incubation period, the MOLT-4 cells and platelets showed IC50 values of 10.1 nM and 1217 nM, respectively.
XZ739 potently reduces the viability of T-ALL MOLT-4, B-ALL RS4;11, SCLC NCI-H146 cells, and platelets. In MOLT-4 cells, it achieves a DC50 of 2.5 nM after 16 hours of treatment. The compound induces cell death through caspase-mediated apoptosis. |
| ln Vivo |
In vivo activity data for XZ739 are limited. As a PROTAC degrader of BCL-XL, it is expected to have antitumor activity in xenograft models of BCL-XL-dependent cancers. Further in vivo studies are needed to fully characterize its efficacy and safety profile.
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| Enzyme Assay |
In vitro assays measure BCL-XL degradation using immunoblotting or mass spectrometry. DC50 values are determined by treating cells with increasing concentrations of XZ739 and quantifying the remaining BCL-XL protein. Apoptosis is assessed through caspase activity assays.
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| Cell Assay |
Western Blot Analysis[1]
Cell Types: MOLT-4 cells Tested Concentrations: 1.2, 3.7, 11, 33, 100, 300 nM Incubation Duration: 16 hrs (hours) Experimental Results: Dose-dependently induced BCL-XL degradation. Cell-based assays use MOLT-4 cells to measure BCL-XL degradation and cell viability. DC50 values are determined after 16 hours of treatment. Apoptosis is confirmed through caspase-mediated cell death assays. Cell viability is assessed in various cancer cell lines. |
| Animal Protocol |
In vivo efficacy is evaluated in xenograft models of BCL-XL-dependent cancers. The compound's ability to inhibit tumor growth through BCL-XL degradation and apoptosis induction is assessed. Further studies are needed to fully characterize its in vivo antitumor activity.
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| ADME/Pharmacokinetics |
Pharmacokinetic data for XZ739 are limited. As a PROTAC molecule with a molecular weight of approximately 1360 Da (C65H76ClF3N8O12S3), it may have challenges with oral bioavailability and tissue distribution typical of large PROTAC molecules.
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| Toxicity/Toxicokinetics |
Preclinical toxicity data for XZ739 are limited. As a BCL-XL degrader, it may have on-target toxicities including thrombocytopenia due to the role of BCL-XL in platelet survival. Standard laboratory safety precautions should be followed. Further toxicological studies are needed.
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| References | |
| Additional Infomation |
XZ739 is a Cereblon-dependent PROTAC BCL-XL degrader with a DC50 of 2.5 nM in MOLT-4 cells. It induces cell death through caspase-mediated apoptosis. The compound is a valuable research tool for studying BCL-XL biology and has potential therapeutic applications in BCL-XL-dependent cancers including T-ALL, B-ALL, and SCLC.
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| Molecular Formula |
C65H76CLF3N8O12S3
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|---|---|
| Molecular Weight |
1349.98856258392
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| Exact Mass |
1348.438
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| CAS # |
2365172-19-4
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| PubChem CID |
139331521
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| Appearance |
Light yellow to yellow solid powder
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| LogP |
9.9
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| Hydrogen Bond Donor Count |
4
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| Hydrogen Bond Acceptor Count |
21
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| Rotatable Bond Count |
30
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| Heavy Atom Count |
92
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| Complexity |
2730
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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)CCN(C)CCOCCOCCOCCNC3=CC=CC4C(N(C(C=43)=O)C3C(NC(CC3)=O)=O)=O)(=O)=O)=O)=CC=2)CC1
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| InChi Key |
RTASGZOITGGVPZ-YJUSKGKKSA-N
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| InChi Code |
InChI=1S/C65H76ClF3N8O12S3/c1-64(2)26-24-52(44-12-16-47(66)17-13-44)46(41-64)42-75-29-31-76(32-30-75)49-18-14-45(15-19-49)60(79)73-92(85,86)51-20-21-54(57(40-51)91(83,84)65(67,68)69)71-48(43-90-50-8-5-4-6-9-50)25-28-74(3)33-35-88-37-39-89-38-36-87-34-27-70-55-11-7-10-53-59(55)63(82)77(62(53)81)56-22-23-58(78)72-61(56)80/h4-21,40,48,56,70-71H,22-39,41-43H2,1-3H3,(H,73,79)(H,72,78,80)/t48-,56?/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-[2-[2-[2-[2-[[2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindol-4-yl]amino]ethoxy]ethoxy]ethoxy]ethyl-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 Note: Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture. |
| 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 : 20 mg/mL (14.81 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: 2 mg/mL (1.48 mM) in 10% DMSO + 40% PEG300 +5% Tween-80 + 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 20.0 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. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 0.7407 mL | 3.7037 mL | 7.4075 mL | |
| 5 mM | 0.1481 mL | 0.7407 mL | 1.4815 mL | |
| 10 mM | 0.0741 mL | 0.3704 mL | 0.7407 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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