| Size | Price | Stock | Qty |
|---|---|---|---|
| 5mg |
|
||
| 10mg |
|
||
| 50mg |
|
||
| 100mg |
|
||
| Other Sizes |
| Targets |
P62-ZZ domain[1].
p62-ZZ domain (Sequestosome-1). XRK3F2 is a specific inhibitor of the ZZ domain of the ubiquitin-binding protein p62. It inhibits MM cell growth and bone marrow stromal cell (BMSC) growth enhancement of human MM cells. |
|---|---|
| ln Vitro |
Runx2 suppression at days 0 and 4 was avoided in the MM-preOB coculture when XRK3F2 was present. Moreover, XRK3F2 inhibited the overexpression of Gfi1 produced by MM. In all treatment scenarios, Gfi1 mRNA induction in BMSCs was inhibited by XRK3F2. On the other hand, Runx2 inhibition mediated by TNFα and IL7, as well as MM1.S CM, is prevented by XRK3F2. Additionally, XRK3F2 therapy decreased the myeloma pro-survival and pro-inflammatory factor IL6 mRNA. Moreover, XRK3F2 restores Runx2 repression in MC4 pre-OB and blocks TNFα-mediated elevation of Gfi1. Moreover, XRK3F2 prevents MM-induced GFI1 from occupying the Runx2-P1 promoter. In hBMSCs from MM patients, XRK3F2 therapy can dramatically restore Runx2 H3K9ac levels, and XRK3F2 can rescue the initial stages of osteogenesis [1].
XRK3F2 blunts MM-induced Runx2 suppression in vitro. It inhibits MM cell growth and BMSC growth enhancement of human MM cells. It blocks TNFα and MM activation of downstream signaling from the p62-signaling hub. |
| ln Vivo |
XRK3F2 induces new bone formation and remodeling in the presence of tumor in vivo. It has demonstrated efficacy in multiple myeloma research. It is used as a tool to study bone disease in multiple myeloma.
|
| Enzyme Assay |
In vitro enzyme assays are not typically performed for this compound. Its mechanism involves inhibition of protein-protein interactions within the p62-ZZ domain. Binding assays using purified p62 protein and peptide ligands are used to assess inhibitor activity.
|
| Cell Assay |
In vitro cell-based assays are performed using multiple myeloma cell lines and bone marrow stromal cells (BMSCs). Cells are treated with XRK3F2. Cell viability is measured using MTT or CellTiter-Glo assays. Runx2 expression is measured by Western blotting or qRT-PCR. Signaling pathways downstream of p62 are assessed.
|
| Animal Protocol |
In vivo efficacy studies are performed in mouse models of multiple myeloma. XRK3F2 is administered intraperitoneally or orally. Tumor burden is assessed by imaging or flow cytometry. Bone formation and remodeling are evaluated by micro-CT and histomorphometry. Bone marrow is collected for biomarker analysis.
|
| ADME/Pharmacokinetics |
XRK3F2 has a molecular weight of 435.89 and a molecular formula of C23H24ClF2NO3. It is soluble in DMSO (150 mg/mL). It is a solid. Detailed pharmacokinetic parameters such as oral bioavailability and half-life are available from specialized databases. It is stored at -20°C.
|
| Toxicity/Toxicokinetics |
Detailed toxicological profiles of XRK3F2 are not extensively reported. As a research compound, it is expected to have a manageable safety profile at the concentrations used in cell-based assays. Cytotoxicity is assessed in parallel with the desired activity to determine the selectivity index.
|
| References | |
| Additional Infomation |
XRK3F2 is a research-grade p62-ZZ domain inhibitor. It is used in multiple myeloma research to study bone disease. It is not approved for clinical use. Its molecular formula is C23H24ClF2NO3 and its molecular weight is 435.89.
|
| Molecular Formula |
C23H24CLF2NO3
|
|---|---|
| Molecular Weight |
435.89
|
| Exact Mass |
435.141
|
| CAS # |
2375193-43-2
|
| PubChem CID |
135397144
|
| Appearance |
White to off-white solid powder
|
| Hydrogen Bond Donor Count |
3
|
| Hydrogen Bond Acceptor Count |
6
|
| Rotatable Bond Count |
10
|
| Heavy Atom Count |
30
|
| Complexity |
440
|
| Defined Atom Stereocenter Count |
0
|
| SMILES |
C1=CC(=CC=C1COC2=C(C=C(C=C2)CNCCO)OCC3=CC=C(C=C3)F)F.Cl
|
| InChi Key |
OKFZPRHMUQRCLJ-UHFFFAOYSA-N
|
| InChi Code |
InChI=1S/C23H23F2NO3.ClH/c24-20-6-1-17(2-7-20)15-28-22-10-5-19(14-26-11-12-27)13-23(22)29-16-18-3-8-21(25)9-4-18;/h1-10,13,26-27H,11-12,14-16H2;1H
|
| Chemical Name |
2-[[3,4-bis[(4-fluorophenyl)methoxy]phenyl]methylamino]ethanol;hydrochloride
|
| 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 : 150 mg/mL (344.12 mM)
H2O : 0.91 mg/mL (2.09 mM) |
|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (5.74 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 25.0 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: ≥ 2.5 mg/mL (5.74 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 25.0 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: ≥ 2.5 mg/mL (5.74 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.2942 mL | 11.4708 mL | 22.9416 mL | |
| 5 mM | 0.4588 mL | 2.2942 mL | 4.5883 mL | |
| 10 mM | 0.2294 mL | 1.1471 mL | 2.2942 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
