XRK3F2

Catalog No.S8756

XRK3F2 Chemical Structure

Molecular Weight(MW): 435.89

XRK3F2 is an inhibitor of the p62-ZZ domain that blunts MM-induced Runx2 suppression in vitro, and induces new bone formation and remodeling in the presence of tumor in vivo.

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Biological Activity

Description XRK3F2 is an inhibitor of the p62-ZZ domain that blunts MM-induced Runx2 suppression in vitro, and induces new bone formation and remodeling in the presence of tumor in vivo.
Targets
p62-ZZ [1]
()
In vitro

XRK3F2 blocks TNFα and MM (Multiple myeloma) activation of downstream signaling from the p62-signaling hub. In addition, XRK3F2 also directly decreases osteoclast formation. It directly inhibits cell growth of primary CD138+ MM cells and human MM cell lines in vitro, without negatively affecting the growth of BMSC[1]. XRK3F2 has no effect on non-MM bearing bone. XRK3F2 blocks TNFα but not IL-1β stimulated NFκB phosphorylation in MM patient BMSC and inhibits IκBα degradation by interfering with p-IκBα activation in MM cells treated with TNFα. XRK3F2 also significantly inhibits TNFα-enhanced VCAM-1, IL-6, and RANKL expression by BMSCs from MM patients compared to vehicle. XRK3F2 directly activates caspases 3, 7, and 9 in MM cells and decreases NFκB signaling in MM results in the aggregation of caspase 8 and its downstream effector caspases. Thus, high concentrations of XRK3F2 induce apoptosis in MM cells[2].

In vivo

In vivo, XRK3F2 induces new bone formation and remodeling in the presence of tumor. The t1/2 of XRK3F2 in mice is 10.3 hours. XRK3F2 induces dramatic, local new bone formation in bones bearing MM in vivo but does not induce new bone formation in bones from the same animals that are not directly inoculated with MM cells. The results demonstrate that XRK3F2 alters the effect of MM on bone[2].

Protocol

Cell Research:

[1]

+ Expand
  • Cell lines: MC4 cells
  • Concentrations: 5 μM
  • Incubation Time: 48 h
  • Method:

    MC4 cells are cultured in with or without 5TGM1 MM cells (in direct contact) for 48 h under proliferation conditions +/– XRK3F2 (5 μM). MM cells are then removed by washing and media is changed to osteogenic differentiation conditions +/– XRK3F2. MC4 cells are collected at the time of MM cell removal (day 0), and after 4 days of differentiation culture in the absence of MM cells (day 4).


    (Only for Reference)
Animal Research:

[2]

+ Expand
  • Animal Models: Specific-pathogen-free, male C57BL/KaLwRij mice (6–12 weeks of age) with implanted tumor
  • Formulation: 0.01ml/g in 15% hydroxyl propyl β cyclodextrin in saline
  • Dosages: 27 mg/kg/day or 40 mg/kg/day
  • Administration: i.p.
    (Only for Reference)

Solubility (25°C)

In vitro DMSO 87 mg/mL (199.59 mM)
Water Insoluble
Ethanol Insoluble

* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.

Chemical Information

Molecular Weight 435.89
Formula

C23H24ClF2NO3

CAS No. No
Storage powder
in solvent
Synonyms N/A

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Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

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Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID