| Protocol | In Vitro | In vitro activity: UM-164 is a potent Src/p38 inhibitor with potential anticancer activity for Triple-Negative Breast Cancer (TNBC). It is a promising lead compound for developing the first targeted therapeutic strategy against TNBC. c-Src has been shown to play a pivotal role in breast cancer progression, metastasis, and angiogenesis. In the clinic, however, the limited efficacy and high toxicity of existing c-Src inhibitors have tempered the enthusiasm for targeting c-Src. UM-164 binds the inactive kinase conformation of c-Src. Kinome-wide profiling of UM-164 identified that Src and p38 kinase families were potently inhibited by UM-164. UM-164 alters the cell localization of c-Src in TNBC cells. In xenograft models of TNBC, UM-164 resulted in a significant decrease of tumor growth compared with controls, with limited in vivo toxicity. Kinase Assay: UM-164 is a potent and dual inhibitor of the Src/p38 kinase with potential anticancer activity. UM-164 binds the inactive kinase conformation of c-Src. Kinome-wide profiling of UM-164 identified that Src and p38 kinase families were potently inhibited by UM-164. Cell Assay: MDA-MB 468 cells were trypsinized and allowed to adhere overnight to #1.5 cover glass in a 6-well plate. Cells were then treated with 5 μmol/L dasatinib, 5 μmol/L UM-164, or vehicle (DMSO) for 4 hours. Cells were then fixed with 4% paraformaldehyde for 15 minutes at room temperature followed by three washes with PBS. The fixed cells were treated with 1 μmol/L of an irreversible turn-on Src fluorophore for 1 hour followed by three washes with PBS. Cells were then mounted on slides with UltraCruz Hard-set Mounting Medium w/DAPI (Santa Cruz Biotechnology; sc-359850) and stored for 30 minutes at 4°C in the dark. |
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| In Vivo | In xenograft models of TNBC, UM-164 resulted in a significant decrease of tumor growth compared with controls, with limited in vivo toxicity. |
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| Animal model | NCr/nude mice, 6 weeks of age |
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| Formulation | Dissolved in a mixture of DMSO/propylene glycol (1:9) |
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| Dosages | 10 mg/kg, 15 mg/kg, or 20 mg/kg; i.p. injection |
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These protocols are for reference only. InvivoChem does not
independently validate these methods.
Preparing Stock Solutions
| Solvent volume to be added |
Mass (the weight of a compound) |
| Mother liquor concentration |
1mg | 5mg | 10mg | 20mg |
| 1mM | 1.5608 mL | 7.8041 mL | 15.6082 mL | 31.2163 mL |
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| 5mM | 0.3122 mL | 1.5608 mL | 3.1216 mL | 6.2433 mL |
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| 10mM | 0.1561 mL | 0.7804 mL | 1.5608 mL | 3.1216 mL |
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| 20mM | 0.0780 mL | 0.3902 mL | 0.7804 mL | 1.5608 mL |
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Quality Control Documentation
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