| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| 10mg |
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| 25mg | |||
| Other Sizes |
| Targets |
IC50: 30 pM (BRD4, RS4;11 leukemia cells)[1] PROTAC
ZBC260 targets the BET (Bromodomain and Extra-Terminal) family of proteins, specifically BRD2, BRD3, and BRD4. As a PROTAC (Proteolysis-Targeting Chimera), it binds to both the BET protein and the E3 ubiquitin ligase Cereblon, marking the BET protein for ubiquitination and subsequent degradation by the proteasome. |
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| ln Vitro |
In the RS4;11 leukemia cells, BETd-260 (ZBC260; Compound 23) can cause the BRD2, BRD3, and BRD4 proteins to degrade at concentrations between 30 and 100 pM. With IC50s of 51 pM and 2.2 nM, respectively, BETd-260 exhibits inhibitory effect against the development of MOLM-13 and RS4;11 leukemia cells. It also promotes apoptosis in both RS4;11 and MOLM-13 cell lines at 3–10 nM[1]. In HCC cells, BETd-260 reciprocally regulates the expression of many apoptotic genes, i.e., upregulating the expression of pro-apoptotic Bad and downregulating the expression of anti-apoptotic Mcl-1, Bcl-2, c-Myc, and XIAP[2].
In vitro, ZBC260 (BETd-260) promotes the degradation of BRD2, BRD3, and BRD4 proteins. In RS4;11 leukemia cells, it achieves an IC50 of 51 pM for inhibition of cell growth. In MOLM-13 cells, the IC50 is 2.2 nM. The compound demonstrates exceptional activity against BRD4 protein, with degradation observed at concentrations as low as 30 pM. |
| ln Vivo |
BETd-260 (5 mg/kg, intravenous, every other day, three times a week for three weeks) causes minimal body weight loss or other symptoms of toxicity in mice bearing RS4;11 xenograft tumors, and causes rapid tumor regression with a maximum of >90% remission. In the RS4;11 xenograft mouse model, BETd-260 (5 mg/kg, iv) significantly downregulates the c-Myc protein and cleaves PARP and caspase-3, breaking down the BRD2, BRD3, and BRD4 proteins for over 24 hours[1].
In vivo, ZBC260 induces rapid tumor regression in xenograft models of RS4;11 tumors. Its potent antitumor activity is demonstrated by its ability to suppress tumor growth in preclinical models, highlighting its potential as a therapeutic agent for cancers driven by BET proteins. |
| Enzyme Assay |
In vitro enzyme/receptor binding assays for ZBC260 are not typically performed as traditional binding assays, as its mechanism is based on protein degradation rather than simple inhibition. However, its activity can be assessed by measuring the degradation of BRD4 protein in cell-free systems or by evaluating its binding to Cereblon and BET proteins using biophysical techniques such as surface plasmon resonance (SPR) or isothermal titration calorimetry (ITC).
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| Cell Assay |
In cell growth experiments, cells are seeded in 96-well cell culture plates at a density of 10000−20000 cells/well in 100 μL of culture medium. BETd-260 is serially diluted in the appropriate medium, and 100 μL of the diluted solution containing BETd-260 is added to the appropriate wells of the cell plate. After addition of BETd-260, the cells are incubated for 4 days at 37°C in an atmosphere of 5% CO2. Cell growth is evaluated by a lactate dehydrogenase-based WST-8 assay using a multimode microplate reader. The WST-8 reagent is added to the plate, incubated for at least 1 h, and read at 450 nm. The readings are normalized to the DMSO-treated cells, and the IC50 is calculated by nonlinear regression analysis using GraphPad Prism 6 software[1].
In vitro cellular assays for ZBC260 are performed using cancer cell lines such as RS4;11, MOLM-13, and HCC cells. Cells are treated with the compound, and BRD2, BRD3, and BRD4 protein levels are assessed by Western blotting to measure degradation. Cell viability is measured using standard assays such as MTT or CellTiter-Glo, and apoptosis is evaluated by flow cytometry using annexin V staining or caspase activity assays. |
| Animal Protocol |
In vivo animal experiments for ZBC260 are conducted in mouse xenograft models. A typical protocol involves subcutaneous implantation of RS4;11 tumor cells in immunodeficient mice, followed by administration of the compound via intraperitoneal or oral routes. Tumor volume is measured periodically to assess antitumor efficacy, and tumor tissues are collected for analysis of BRD4 degradation and apoptosis markers.
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| ADME/Pharmacokinetics |
The pharmacokinetic properties of ZBC260 have been characterized in preclinical studies. The compound has a molecular weight of 798.89 and molecular formula C43H46N10O6. It is soluble in DMSO and should be stored as a powder at -20°C. Further PK details, including half-life, bioavailability, and tissue distribution, are available from the manufacturer's data sheets.
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| Toxicity/Toxicokinetics |
Toxicological data for ZBC260 are not extensively reported in the available literature. As a research-use compound, its safety profile has not been formally evaluated in comprehensive preclinical toxicology studies. The compound is intended for research purposes only and is not approved for human therapeutic use. Standard laboratory safety precautions should be followed when handling this compound.
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| References |
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| Additional Infomation |
ZBC260 is also known as BETd-260 and Compound 23. It is a PROTAC degrader of BET proteins with anticancer activity. The compound is a research tool for studying the role of BET proteins in cancer and other diseases. It is not approved for clinical use and is supplied for research purposes only.
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| Molecular Formula |
C43H46N10O6
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|---|---|
| Molecular Weight |
798.888748645782
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| Exact Mass |
798.36
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| Elemental Analysis |
C, 64.65; H, 5.80; N, 17.53; O, 12.02
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| CAS # |
2093388-62-4
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| PubChem CID |
131698639
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| Appearance |
Off-white to light yellow solid powder
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| LogP |
5.3
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| Hydrogen Bond Donor Count |
4
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| Hydrogen Bond Acceptor Count |
11
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| Rotatable Bond Count |
14
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| Heavy Atom Count |
59
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| Complexity |
1550
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| Defined Atom Stereocenter Count |
0
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| SMILES |
CCN1C(=CC(=N1)C2CC2)NC3=NC(=NC4=C3C5=CC(=C(C=C5N4)C6=C(ON=C6C)C)OC)C(=O)NCCCCCC7=C8CN(C(=O)C8=CC=C7)C9CCC(=O)NC9=O
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| InChi Key |
UZXANFBIRSYHGO-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C43H46N10O6/c1-5-53-34(20-30(50-53)25-13-14-25)46-39-37-27-19-33(58-4)28(36-22(2)51-59-23(36)3)18-31(27)45-38(37)48-40(49-39)42(56)44-17-8-6-7-10-24-11-9-12-26-29(24)21-52(43(26)57)32-15-16-35(54)47-41(32)55/h9,11-12,18-20,25,32H,5-8,10,13-17,21H2,1-4H3,(H,44,56)(H,47,54,55)(H2,45,46,48,49)
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| Chemical Name |
4-[(5-cyclopropyl-2-ethylpyrazol-3-yl)amino]-7-(3,5-dimethyl-1,2-oxazol-4-yl)-N-[5-[2-(2,6-dioxopiperidin-3-yl)-1-oxo-3H-isoindol-4-yl]pentyl]-6-methoxy-9H-pyrimido[4,5-b]indole-2-carboxamide
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| Synonyms |
ZBC-260 ZBC 260 ZBC260
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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: (1). This product requires protection from light (avoid light exposure) during transportation and storage. (2). 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 : ~25 mg/mL (~31.29 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 0.83 mg/mL (1.04 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 8.3 mg/mL clear DMSO stock solution to 400 μL of PEG300 and mix evenly; then add 50 μL of Tween-80 to the above solution and mix evenly; then add 450 μL of 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: ≥ 0.83 mg/mL (1.04 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 8.3 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.2517 mL | 6.2587 mL | 12.5174 mL | |
| 5 mM | 0.2503 mL | 1.2517 mL | 2.5035 mL | |
| 10 mM | 0.1252 mL | 0.6259 mL | 1.2517 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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