| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg | |||
| Other Sizes |
Purity: ≥98%
| Targets |
QCA570 targets BET proteins, specifically BRD4, BRD3, and BRD2, for degradation via the PROTAC mechanism. It is a potent degrader of BRD4 BD1 protein with an IC50 of 10 nM. By inducing the degradation of these proteins, which are key epigenetic readers, it disrupts pathogenic signaling pathways involved in cancer cell proliferation and survival. This mechanism of action is fundamentally different from that of traditional enzyme inhibitors.
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| ln Vitro |
In leukemia cells, QCA570 is a very strong and effective BET degrader that can break down BET proteins at low picomolar (pM) concentrations. MV4;11, MOLM-13, and RS4;11 cell lines are all inhibited in terms of cell growth by QCA570, with IC50 values of 8.3, 62, and 32 pM, respectively. The most successful BET degrader discovered to far is QCA570 [1].
In vitro, QCA570 is an extremely effective BET degrader. It induces the degradation of BET proteins at low picomolar concentrations in leukemia cells. It inhibits cell growth in human acute leukemia cell lines, including MV4;11, MOLM-13, and RS4, at pM levels. This demonstrates its exceptional potency and efficacy in vitro. The compound's IC50 for BRD4 BD1 protein is 10 nM. |
| ln Vivo |
In vivo, QCA570 is expected to have potent anti-tumor activity due to its ability to degrade BET proteins. It has been shown to induce complete and durable tumor regression in preclinical models. This highlights its potential as a highly effective therapeutic agent for cancers that are driven by BET proteins, such as acute leukemia. However, specific in vivo data is not detailed in the available summaries.
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| Enzyme Assay |
Cell-free assays for QCA570 are not the primary method for characterizing its activity, as it is a PROTAC that functions within cells. However, its ability to induce the formation of a ternary complex between the target protein, the E3 ligase, and the PROTAC can be studied in vitro using biophysical methods like surface plasmon resonance (SPR) or isothermal titration calorimetry (ITC). The efficiency of ubiquitination can be measured in a cell-free ubiquitination assay using purified components.
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| Cell Assay |
In vitro cell-based assays for QCA570 are performed to measure its ability to degrade BET proteins and inhibit cell growth. Leukemia cell lines, such as MV4;11 and MOLM-13, are treated with varying concentrations of QCA570. The degradation of BET proteins is assessed by Western blotting, where the levels of BRD2, BRD3, and BRD4 are measured. Cell growth and viability are measured using standard assays like CellTiter-Glo or by counting the number of viable cells. The compound's exceptional potency is demonstrated by its activity at picomolar concentrations.
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| Animal Protocol |
In vivo animal experiments for QCA570 would involve xenograft models of leukemia or other cancers driven by BET proteins. Immunodeficient mice are implanted with human leukemia cells. When the tumors are established, QCA570 is administered, and tumor growth is monitored. The primary endpoint is the reduction in tumor volume. The compound has been shown to induce complete and durable tumor regression.
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| ADME/Pharmacokinetics |
Pharmacokinetic (PK) data for QCA570 is not provided in the available literature. As a PROTAC molecule, its properties, such as oral bioavailability and half-life, would be important for its development. The compound is available as a research reagent. For storage, it is typically kept as a powder.
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| Toxicity/Toxicokinetics |
Toxicological data for QCA570 is not available in the public literature. As a research compound that induces protein degradation, its safety profile would be a critical factor in its development. However, no specific LD50, organ toxicity, or genotoxicity data are reported. Its use is strictly for research purposes, and it is not intended for human therapeutic use.
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| References | |
| Additional Infomation |
QCA570 is a research-grade compound and a highly potent BET degrader developed as a PROTAC. It is a valuable tool for studying the role of BET proteins in cancer and for validating targeted protein degradation as a therapeutic strategy. Its exceptional potency at picomolar concentrations and ability to induce complete tumor regression in preclinical models highlight its potential. It has not been approved for clinical use. All information is for research reference and not for diagnostic or clinical use.
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| Molecular Formula |
C39H33N7O4S
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|---|---|
| Molecular Weight |
695.788826704025
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| Exact Mass |
695.231
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| CAS # |
2207569-08-0
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| PubChem CID |
134348221
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| Appearance |
White to off-white solid powder
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| LogP |
3.9
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
8
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| Rotatable Bond Count |
9
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| Heavy Atom Count |
51
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| Complexity |
1460
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| Defined Atom Stereocenter Count |
0
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| SMILES |
S1C(C#CC2C=NN(C=2)CCCC#CC2=CC=CC3C(N(CC=32)C2C(NC(CC2)=O)=O)=O)=C(CC2C=CC=CC=2)C2COCC3=NN=C(C)N3C1=2
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| InChi Key |
RTVTYLRQKKDYMQ-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C39H33N7O4S/c1-25-42-43-35-24-50-23-32-30(19-26-9-4-2-5-10-26)34(51-39(32)46(25)35)16-14-27-20-40-44(21-27)18-7-3-6-11-28-12-8-13-29-31(28)22-45(38(29)49)33-15-17-36(47)41-37(33)48/h2,4-5,8-10,12-13,20-21,33H,3,7,15,17-19,22-24H2,1H3,(H,41,47,48)
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| Chemical Name |
3-(4-(5-(4-((3-Benzyl-9-methyl-4H,6H-thieno[2,3-e][1,2,4]-triazolo[3,4-c][1,4]oxazepin-2-yl)ethynyl)-1H-pyrazol-1-yl)pent-1-yn-1-yl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione
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| Synonyms |
QCA570 QCA-570 QCA 570
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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: This product requires protection from light (avoid light exposure) during transportation and storage. |
| 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 : ~40 mg/mL (~57.49 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: 2 mg/mL (2.87 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 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. Solubility in Formulation 2: ≥ 2 mg/mL (2.87 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 20.0 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 | 1.4372 mL | 7.1861 mL | 14.3722 mL | |
| 5 mM | 0.2874 mL | 1.4372 mL | 2.8744 mL | |
| 10 mM | 0.1437 mL | 0.7186 mL | 1.4372 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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