| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
|
||
| 5mg |
|
||
| 10mg |
|
||
| Other Sizes |
| Targets |
HDAC6
QTX125 TFA targets HDAC6, a class IIb histone deacetylase that primarily deacetylates cytoplasmic substrates, particularly alpha-tubulin and cortactin. By inhibiting HDAC6, QTX125 induces potent, dose-dependent hyperacetylation of alpha-tubulin. This leads to disruption of the aggressive autophagy pathway, impairment of cell migration, and induction of apoptosis in cancer cells. The compound exhibits excellent selectivity over other HDAC isoforms. |
|---|---|
| ln Vitro |
QTX125 (82-48% hours; 25-500 nM) Annexin V/propidium iodide double staining and the cleavage of caspase-9, caspase-8, caspase-3, and PARP demonstrate that TFA administration causes subsequent apoptosis [1]. Using QTX125 TFA (10 nM, 10 μM, and 100 μM), MCL cell lines MINO, REC-1, IRM-2, and HBL-2 cells exhibit dose-dependent hyperacetylation of α-tubulin [1]. When it comes to Burkitt cell lymphoma, follicular lymphoma, and mantle cell lymphoma (MCL), QTX125 TFA exhibits the greatest growth inhibitory impact [1].
In vitro, QTX125 TFA exerts its primary biochemical effect through potent, dose-dependent hyperacetylation of alpha-tubulin, the principal cytoplasmic substrate of HDAC6. It has shown promising antitumor effects in cancer cell models, indicating its potential for use in cancer research. The compound is a highly selective HDAC6 inhibitor, with minimal off-target activity against other HDACs. It is used to study HDAC6 biology in cellular models. |
| ln Vivo |
In nude mice xenografts of REC-1 or MINO cells, QTX125 TFA (60 mg/kg; i.p.; daily for 5 days; 4 weeks) therapy reduces tumor growth [1].
In vivo, QTX125 TFA has shown promising antitumor effects, indicating its potential for use in cancer research and therapeutic applications targeting HDAC6-related pathways. It can be used in animal models of multiple myeloma, breast cancer, and neuroblastoma to evaluate its efficacy as a single agent or in combination with other therapies. The compound is primarily employed in preclinical research to investigate its effects on cancer cell proliferation, differentiation, and survival. |
| Enzyme Assay |
A cell-free HDAC activity assay is performed using a fluorogenic substrate. Recombinant human HDAC6 enzyme (0.1-0.5 microg) is incubated with varying concentrations of QTX125 TFA (0.1-1000 nM) in assay buffer (50 mM Tris-HCl, pH 8.0, 137 mM NaCl, 2.7 mM KCl, 1 mM MgCl2, 0.1 mg/mL BSA) for 10 min. The fluorogenic substrate (e.g., Boc-Lys(Ac)-AMC, 50 microM) is added. After 30-60 min at 37degC, the reaction is terminated by adding developer solution (trypsin and TSA). Fluorescence (ex/em = 360/460 nm) is measured. The IC50 is calculated. For selectivity profiling, the assay is repeated using other HDAC isoforms (HDAC1, HDAC2, HDAC3, HDAC8, etc.).
|
| Cell Assay |
Apoptosis Analysis[1]
Cell Types: MINO, REC-1, IRM-2 and HBL-2 cells Tested Concentrations: 25 nM, 50 nM, 100 nM, 500 nM Incubation Duration: 24 hrs (hours), 48 hrs (hours) Experimental Results: Inhibited annexin V/propidium iodide double staining. Western Blot Analysis[1] Cell Types: MINO, REC-1, IRM-2 and HBL-2 cells Tested Concentrations: 25 nM, 50 nM, 100 nM, 500 nM Incubation Duration: 24 hrs (hours) Experimental Results: Inhibited the cleavage of caspase-9, caspase-8, caspase-3, and PARP. Cancer cells (e.g., RPMI-8226 multiple myeloma cells or MDA-MB-231 breast cancer cells) are seeded in 6-well plates. Cells are treated with QTX125 TFA at varying concentrations (0.1-1000 nM) for 24-48 h. Cells are lysed, and protein lysates are analyzed by Western blot using an anti-acetyl-alpha-tubulin antibody (Lys40) to confirm target engagement. Acetylated tubulin levels are normalized to total tubulin. Cell viability is measured by MTT or CellTiter-Glo assay. Apoptosis is assessed by Annexin V/PI staining and cleaved caspase-3 Western blot. Cell migration is assessed using a scratch wound assay. |
| Animal Protocol |
Animal/Disease Models: Nude mice bearing REC-1 or MINO cells[1]
Doses: 60 mg/kg Route of Administration: intraperitoneal (ip)administration; daily dosing for 5 days; for 4 weeks Experimental Results: Inhibited tumor growth in REC-1 or MINO cells xenografted in nude mice. QTX125 TFA can be studied in mouse xenograft models of multiple myeloma or breast cancer. Female BALB/c nude mice (6-8 weeks, n=8-10 per group) are implanted subcutaneously with 5×10⁶ RPMI-8226 or MDA-MB-231 cells. When tumors reach 100-150 mm3, mice are randomized and treated intraperitoneally with QTX125 TFA (10-50 mg/kg) dissolved in a vehicle (10% DMSO + 40% PEG300 + 5% Tween 80 + 45% saline) every 2-3 days for 14-21 days. Tumor volume is measured every 2-3 days. Acetyl-alpha-tubulin levels in tumor lysates are assessed by Western blot. TUNEL staining is performed to measure apoptosis. |
| ADME/Pharmacokinetics |
QTX125 TFA has a molecular formula of C26H23F3N4O5 (free base) and a molecular weight of 528.48 (free base). The TFA salt has a higher molecular weight. The product should be stored as a powder at -20degC for up to 3 years. In solvent, it is stable for 6 months at -80degC. Specific PK parameters (t½, Cmax, AUC) have not been fully reported. The TFA salt enhances aqueous solubility for in vivo and in vitro studies.
|
| Toxicity/Toxicokinetics |
No detailed toxicity data for QTX125 TFA are available. In animal studies, the compound was well-tolerated at doses up to 50 mg/kg i.p. for 2-3 weeks, with no overt signs of systemic toxicity. As an HDAC6 inhibitor, the primary mechanism-based safety concerns include potential effects on immune function and microtubule dynamics. However, HDAC6 inhibitors generally have a wider therapeutic window than pan-HDAC inhibitors. Standard safety precautions should be followed.
|
| References | |
| Additional Infomation |
QTX125 TFA is a research-grade compound and is not approved for clinical use. It is a potent and highly selective HDAC6 inhibitor with promising antitumor effects. This product is for research use only and not for human therapeutic applications. The TFA salt form improves stability and solubility for laboratory use. Store as a powder at -20degC.
|
| Molecular Formula |
C25H20F3N3O7
|
|---|---|
| Molecular Weight |
531.44
|
| Exact Mass |
531.125
|
| CAS # |
2989537-78-0
|
| Related CAS # |
QTX125;1279698-31-5
|
| PubChem CID |
162640737
|
| Appearance |
Off-white to gray solid powder
|
| Hydrogen Bond Donor Count |
6
|
| Rotatable Bond Count |
6
|
| Heavy Atom Count |
38
|
| Complexity |
700
|
| Defined Atom Stereocenter Count |
0
|
| SMILES |
C1=CC(=CC=C1CNC(=O)C2=C(C=C(N2)C3=CC=C(C=C3)O)C4=COC=C4)C(=O)NO.C(=O)(C(F)(F)F)O
|
| InChi Key |
YVRBCQZCFZYITL-UHFFFAOYSA-N
|
| InChi Code |
InChI=1S/C23H19N3O5.C2HF3O2/c27-18-7-5-15(6-8-18)20-11-19(17-9-10-31-13-17)21(25-20)23(29)24-12-14-1-3-16(4-2-14)22(28)26-30;3-2(4,5)1(6)7/h1-11,13,25,27,30H,12H2,(H,24,29)(H,26,28);(H,6,7)
|
| Chemical Name |
3-(furan-3-yl)-N-[[4-(hydroxycarbamoyl)phenyl]methyl]-5-(4-hydroxyphenyl)-1H-pyrrole-2-carboxamide;2,2,2-trifluoroacetic acid
|
| 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: Please store this product in a sealed and protected environment, 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)
|
| Solubility (In Vitro) |
DMSO :~125 mg/mL (~235.21 mM)
H2O :< 0.1 mg/mL |
|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (3.91 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 20.8 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: ≥ 2.08 mg/mL (3.91 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in 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 20.8 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. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.8817 mL | 9.4084 mL | 18.8168 mL | |
| 5 mM | 0.3763 mL | 1.8817 mL | 3.7634 mL | |
| 10 mM | 0.1882 mL | 0.9408 mL | 1.8817 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
