| Size | Price | Stock | Qty |
|---|---|---|---|
| 5mg |
|
||
| 10mg |
|
||
| 100mg | |||
| Other Sizes |
| Targets |
QC6352 targets the KDM4 family of histone demethylases, which are enzymes that remove methyl groups from histone proteins. It is a potent inhibitor of KDM4C, with an IC50 of 35 nM. It also inhibits other members of the family: KDM4A (IC50 = 104 nM), KDM4B (IC50 = 56 nM), and KDM4D (IC50 = 104 nM). By inhibiting these enzymes, QC6352 alters the epigenetic landscape of cells, leading to changes in gene expression that can suppress tumor growth and proliferation.
|
|---|---|
| ln Vitro |
QC6352, having an IC50 of 35±8 nM, is a strong inhibitor of KDM4C[1]. In a concentration-dependent way, QC6352 dramatically decreased BCSC1 and BCSC2's capacity to form spheres. QC6352 prevents BCSC self-renewal and proliferation. EGFR (epidermal growth factor receptor) protein levels were decreased in BCSC1 and BCSC2 following QC6352 therapy, as demonstrated by Western blot analysis [2].
In vitro, QC6352 demonstrates potent anti-proliferative activity. It blocks the proliferation and self-renewal of breast cancer stem cells (BCSCs) in a concentration-dependent manner. It dramatically decreases the anchorage-independent growth of BCSC1 and BCSC2. The compound has also shown potent activity in cancer cell lines, with an IC50 of 5 nM in the BR0869f model and 13 nM in the SU60 model after a 5-day incubation. |
| ln Vivo |
For BCSC1 and BCSC2 xenografts, QC6352 has a significant impact on tumor growth and final tumor weight. Body weight of the mice was unaffected by the QC6352 therapy, which was well tolerated. According to the findings, BCSC xenograft tumor growth was inhibited by therapy with the KDM4 inhibitor QC6352 [2].
In vivo, QC6352 is an orally active KDM4 inhibitor that has shown efficacy in PDX models of breast and colon cancer. It effectively inhibits tumor growth and reduces the number of chemoresistant cell populations. This suggests that QC6352 could be a promising therapeutic agent for the treatment of cancer, particularly in combination with other therapies to overcome drug resistance. |
| Enzyme Assay |
Cell-free assays for QC6352 focus on its ability to inhibit the enzymatic activity of KDM4 demethylases. In a typical assay, the recombinant KDM4 enzyme is incubated with a peptide substrate that contains a methylated lysine residue. The reaction is carried out in the presence of the necessary cofactors (e.g., α-ketoglutarate and Fe2+). The demethylation of the peptide is then measured. This can be done using a mass spectrometry-based method to detect the loss of methylation or by using a fluorescence-based assay where the demethylation leads to a change in fluorescence. The IC50 is calculated from the dose-response curve.
|
| Cell Assay |
In vitro cell-based assays for QC6352 are performed to evaluate its anti-proliferative effects. Cancer cell lines, particularly those that are sensitive to KDM4 inhibition, are treated with varying concentrations of the compound for a defined period. Cell viability is measured using standard assays like MTT or CellTiter-Glo. The effect on cancer stem cells (CSCs) can be assessed using sphere formation assays, where the ability of CSCs to form spheres in suspension culture is measured. These assays confirm the compound's ability to inhibit cell growth in a cellular context.
|
| Animal Protocol |
In vivo animal experiments for QC6352 are conducted using patient-derived xenograft (PDX) models. In these models, tumor tissue from a patient is implanted into immunodeficient mice. When the tumors are established, the mice are treated with QC6352, often orally. Tumor growth is monitored by caliper measurements. The compound's effect on tumor growth, as well as its ability to reduce chemoresistant cell populations, is assessed.
|
| ADME/Pharmacokinetics |
QC6352 is an orally active compound, suggesting it has favorable pharmacokinetic properties for oral administration. However, detailed PK parameters such as bioavailability, half-life, and tissue distribution are not provided in the available literature. The compound is soluble in DMSO. For storage, it is typically kept as a powder.
|
| Toxicity/Toxicokinetics |
Toxicological data for QC6352 is not available in the public literature. As a research compound targeting epigenetic enzymes, 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.
|
| References | |
| Additional Infomation |
QC6352 is a research-grade compound developed as a potent and selective inhibitor of the KDM4 family of histone demethylases. It is a valuable tool for studying the role of histone methylation in cancer and other diseases. Its ability to inhibit tumor growth in PDX models and reduce chemoresistant cell populations highlights its therapeutic potential. It has not been approved for clinical use. All information is for research reference and not for diagnostic or clinical use.
|
| Molecular Formula |
C24H25N3O2
|
|---|---|
| Molecular Weight |
387.474205732346
|
| Exact Mass |
387.194
|
| CAS # |
1851373-36-8
|
| PubChem CID |
118598059
|
| Appearance |
Light yellow to yellow solid powder
|
| LogP |
5.3
|
| Hydrogen Bond Donor Count |
2
|
| Hydrogen Bond Acceptor Count |
5
|
| Rotatable Bond Count |
6
|
| Heavy Atom Count |
29
|
| Complexity |
536
|
| Defined Atom Stereocenter Count |
1
|
| SMILES |
O=C(C1=C(NC[C@@H]2CCCC3=C2C=CC(N(C)C4=CC=CC=C4)=C3)C=NC=C1)O
|
| InChi Key |
XSMABFRQESMONQ-SFHVURJKSA-N
|
| InChi Code |
InChI=1S/C24H25N3O2/c1-27(19-8-3-2-4-9-19)20-10-11-21-17(14-20)6-5-7-18(21)15-26-23-16-25-13-12-22(23)24(28)29/h2-4,8-14,16,18,26H,5-7,15H2,1H3,(H,28,29)/t18-/m0/s1
|
| Chemical Name |
3-[[(1R)-6-(N-methylanilino)-1,2,3,4-tetrahydronaphthalen-1-yl]methylamino]pyridine-4-carboxylic acid
|
| Synonyms |
QC 6352; QC-6352; QC6352
|
| HS Tariff Code |
2934.99.9001
|
| 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)
|
| Solubility (In Vitro) |
DMSO : ~16.67 mg/mL (~43.02 mM)
|
|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 1.67 mg/mL (4.31 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 16.7 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: 1.67 mg/mL (4.31 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 16.7 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: ≥ 1.67 mg/mL (4.31 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. Solubility in Formulation 4: 10 mg/mL (25.81 mM) in 50% PEG300 50% Saline (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.5808 mL | 12.9042 mL | 25.8084 mL | |
| 5 mM | 0.5162 mL | 2.5808 mL | 5.1617 mL | |
| 10 mM | 0.2581 mL | 1.2904 mL | 2.5808 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.
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
