ZX079
ZX079 is a dual BRD4 and CBP PROTAC degrader with a BRD4 DC50 value of 0.035 nM and a CBP DC50 value of < 0.02 nM. ZX079 induces dose- and time-dependent degradation of BRD4 and CBP proteins through recruitment of the cereblon E3 ligase. ZX079 induces apoptosis in MV4-11 and MOLM-13 cells, reduces tumor growth in an acute myeloid leukemia xenograft model. ZX079 can be used for the research of acute myeloid leukemia.
(Pink: ligand (HY-181759); Blue: Cereblon ligand (HY-14658); Black: linker (HY-W105740)).
For research use only. We do not sell to patients.
- CAS No.: 3124583-65-6
- Formula: C47H56F3N7O7
- Molecular Weight:887.99
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Storage:
Please store the product under the recommended conditions in the Certificate of Analysis.
To place orders, for customer services and technical support, please contact: MedChemExpress USA
Tel: 609-228-6898 E-mail: [email protected] [email protected]
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Biological Activity
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Chemical Information
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Solvent & Solubility
- Protocols
- Purity & Documentation
- References
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Help & FAQs
Biological Activity
Description
IC50 & Target
[1]|
BRD4 0.035 nM (DC50) |
BRD4(1) 0.9 μM (IC50) |
BRD4(2) 0.5 μM (IC50) |
CBP |
p300 |
Caspase 3 |
Cereblon |
In Vitro
ZX079 (10k) (24 h) exhibits dose- and time-dependent degradation of BRD4 (DC50 = 0.035 nM), CBP, p300 and BRD3 (DC50 < 0.02 nM) without significant degradation of BRD2[1].
ZX079 (0.0001-100 μM) binds potently to BRD4 (1) (IC50 = 0.9 μM), BRD4 (2) (IC50 = 0.5 μM), and CBP bromodomains (IC50 = 1.2 μM) and effectively promotes BRD4-PROTAC-CRBN and CBP-PROTAC-CRBN ternary complex assembly[1].
ZX079 (0.02-200 nM; 96 h) exerts superior antiproliferative activity against MV4-11 cells (IC50 = 0.86 nM) and MOLM-13 cells, while it shows minimal cytotoxicity against normal HUVEC and L929 cells (tested at 0.001-10 μM)[1].
ZX079 (200 nM; 8 h) selectively depletes BRD4, BRD3, CBP, and p300 proteins in MV4-11 cells at the proteome-wide level
ZX079 (37-1000 nM; 48 h) induces apoptosis in MV4-11 and MOLM-13 cells in a dose-dependent manner, accompanied by increased cleavage of Caspase-3 and almost complete reduction of c-Myc protein expression at 2 nM[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:MV4-11 and MOLM-13 acute myeloid leukemia cells, HUVEC, L929 normal cells
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Concentration:10-6, 10-4, 10-2, 100, 102 μM (MV4-11 and MOLM-13 cells); 0.01, 0.01, 0.1, 1, 10, 100 μM (HUVEC and L929 cells)
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Incubation Time:96 h (MV4-11 and MOLM-13 cells); 48 h (HUVEC and L929 cells)
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Result:Exhibited an IC50 of 0.86 nM in MV4-11 cells and 18.93 nM in MOLM-13 cells.
Exhibited minimal cytotoxicity toward HUVEC and L929 cells.
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Cell Line:MV4-11 acute myeloid leukemia cells
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Concentration:0.02, 0.2, 2.0, 20, 200 nM (24 h); 200 nM (time-course); 2 nM, 200 nM (24 h)
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Incubation Time:1 h, 2 h, 4 h, 8 h, 12 h, 24 h (time-course); 24 h (fixed time)
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Result:Achieved 95% degradation of BRD4 and 74% degradation of CBP at 2 nM after 24 h.
Achieved 98% degradation of BRD4 and 99% degradation of CBP at 200 nM after 24 h.
Induced rapid degradation of CBP within 2 h, with near-complete depletion by 4 h.
Reduced BRD4 levels in a time-dependent manner over 24 h.
Exhibited a DC50 of 0.035 nM for BRD4, < 0.02 nM for CBP, and < 0.02 nM each for p300 and BRD3.
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Cell Line:MV4-11 and MOLM-13 acute myeloid leukemia cells
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Concentration:37, 111, 333, 1000 nM
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Incubation Time:48 h
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Result:Potently induced apoptosis in a dose-dependent manner, achieving over 60% apoptosis at 37 nM in MV4-11 cells.
Led to markedly increased cleaved caspase-3 levels and almost completely reduced c-Myc protein expression in MV4-11 cells at 20 nM.
Induced dose-dependent apoptosis in MOLM-13 cells.
Parmacokinetics
In Vivo
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:NOD SCID (female, 4 weeks old, subcutaneous xenograft model)[1]
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Dosage:2 mg/kg (twice weekly); 10 mg/kg (weekly)
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Administration:intraperitoneal injection; 21 days
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Result:Achieved a tumor growth inhibition (TGI) rate of 93% with 2 mg/kg twice-weekly dose.
Achieved a TGI rate of 91% with 10 mg/kg weekly dose.
Caused no significant body weight loss compared to vehicle control.
Induced degradation of BRD4 and CBP proteins in harvested tumors.
Significantly reduced c-Myc protein expression relative to vehicle control.
- Detection of Apoptosis
- TUNEL staining for apoptotic DNA fragmentation
- Annexin V plus membrane-impermeant dye apoptosis staining
- Patient-Derived Xenograft (PDX)
- Apoptosis Solutions
- Patient-Derived Orthotopic Xenograft (PDOX)
- Splenic/Portal-Vein Liver Metastasis Xenograft
- Subcutaneous Cell-Line-Derived Xenograft
- Orthotopic Cell-Line Xenograft
- Intraperitoneal/Peritoneal Dissemination Xenograft
Chemical Information
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CAS No. 3124583-65-6
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Molecular Weight 887.99
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Formula C47H56F3N7O7
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SMILES
O=C(NC(CC1)=O)C1N(C2=O)C(C(C2=C3)=CC=C3NCCCCCCCCCCCC(N(CC4)CCC4C5=NC6=CC=C(C(C=C7C)=CN(C)C7=O)C=C6N5CCOC(F)(F)F)=O)=O
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Shipping
Room temperature in continental US; may vary elsewhere.
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Storage
Please store the product under the recommended conditions in the Certificate of Analysis.
Solvent & Solubility
In Vitro:
DMSO : 100 mg/mL (112.61 mM; Need ultrasonic; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
In Vivo:
Select the appropriate dissolution method based on your experimental animal and administration route.
- For the following dissolution methods, please ensure to first prepare a clear stock solution using an In Vitro approach and then sequentially add co-solvents:
- To ensure reliable experimental results, the clarified stock solution can be appropriately stored based on storage conditions. As for the working solution for In Vivo experiments, it is recommended to prepare freshly and use it on the same day.
- The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.
Add each solvent one by one: 10% DMSO 40% PEG300 5% Tween-80 45% Saline
Solubility: ≥ 2.5 mg/mL (2.82 mM); Clear solution
This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 400 μL PEG300, and mix evenly; then add 50 μL Tween-80 and mix evenly; then add 450 μL Saline to adjust the volume to 1 mL.
Preparation of Saline: Dissolve 0.9 g sodium chloride in ddH₂O and dilute to 100 mL to obtain a clear Saline solution.
Add each solvent one by one: 10% DMSO 90% (20% SBE-β-CD in Saline)
Solubility: ≥ 2.5 mg/mL (2.82 mM); Clear solution
This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 900 μL 20% SBE-β-CD in Saline, and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C, storage for one week): 2 g SBE-β-CD powder is dissolved in 10 mL Saline, completely dissolve until clear.
In Vivo Dissolution Calculator
Please enter the basic information of animal experiments:
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Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.
Please enter your animal formula composition:
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%DMSO +
Recommended: Keep the proportion of DMSO in working solution below 2% if your animal is weak.
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%+
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+%Tween-80 + +
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%Saline +
The co-solvents required include: DMSO, . All of co-solvents are available by MedChemExpress (MCE). , Tween 80. All of co-solvents are available by MedChemExpress (MCE).
Working solution concentration: 0.22 mg/mL
Method for preparing stock solution: mg drug dissolved in μL DMSO. Stock solution concentration: mg/mL.
1. Take μL DMSO stock solution;
2. Add μL .
μL , mix evenly;
3. Then add μL Tween 80, mix evenly;
4. Then add μL
Please ensure that the stock solution in the first step is dissolved to a clear state, and add co-solvents in sequence. You can use ultrasonic heating (ultrasonic cleaner, recommended frequency 20-40 kHz), vortexing, etc. to assist dissolution.
Purity & Documentation
References
Complete Stock Solution Preparation Table
| Optional Solvent | Concentration Solvent Mass | 1 mg | 5 mg | 10 mg | 25 mg |
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| DMSO | 1 mM | 1.1261 mL | 5.6307 mL | 11.2614 mL | 28.1535 mL |
| 5 mM | 0.2252 mL | 1.1261 mL | 2.2523 mL | 5.6307 mL | |
| 10 mM | 0.1126 mL | 0.5631 mL | 1.1261 mL | 2.8153 mL | |
| 15 mM | 0.0751 mL | 0.3754 mL | 0.7508 mL | 1.8769 mL | |
| 20 mM | 0.0563 mL | 0.2815 mL | 0.5631 mL | 1.4077 mL | |
| 25 mM | 0.0450 mL | 0.2252 mL | 0.4505 mL | 1.1261 mL | |
| 30 mM | 0.0375 mL | 0.1877 mL | 0.3754 mL | 0.9384 mL | |
| 40 mM | 0.0282 mL | 0.1408 mL | 0.2815 mL | 0.7038 mL | |
| 50 mM | 0.0225 mL | 0.1126 mL | 0.2252 mL | 0.5631 mL | |
| 60 mM | 0.0188 mL | 0.0938 mL | 0.1877 mL | 0.4692 mL | |
| 80 mM | 0.0141 mL | 0.0704 mL | 0.1408 mL | 0.3519 mL | |
| 100 mM | 0.0113 mL | 0.0563 mL | 0.1126 mL | 0.2815 mL |
ZX079 Related Classifications
HY-181854 Related Classifications
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