product name GSK503
Description: GSK503 is a potent and specific EZH2 methyltransferase inhibitor with potential anticancer activity. Increased activity of the epigenetic modifier EZH2 has been associated with different cancers. In a melanoma mouse model, conditional Ezh2 ablation as much as treatment with the preclinical EZH2 inhibitor GSK503 stabilizes the disease through inhibition of growth and virtually abolishes metastases formation without affecting normal melanocyte biology.
References: Cancer Cell. 2013 May 13;23(5):677-92; Nat Commun. 2015 Jan 22;6:6051.
526.67
Formula
C31H38N6O2
CAS No.
1346572-63-1
Storage
-20℃ for 3 years in powder form
-80℃ for 2 years in solvent
Solubility (In vitro)
DMSO: 100 mg/mL (189.8 mM)
Water: <1 mg/mL
Ethanol: 26 mg/mL warmed (49.4 mM)
Solubility (In vivo)
Synonyms
other peoduct :
| In Vitro |
In vitro activity: GSK503 inhibits the methyltransferase activity of WT and mutant EZH2 with similar potency. In a panel of seven DLBCL cell lines, GSK503 causes growth inhibition and the effects are enhanced by ABT737 or Obatoclax. Kinase Assay: GSK503 is profiled to assess inhibition against a panel of histone acetylases. GSK503 is dissolved in DMSO and tested in 10-dose IC50 mode with 3-fold serial dilution starting at 100 μM, with a final DMSO concentration of 2%. Anacardic Acid is used as positive control for CBP, GCN5, and pCAF and tested in 10-dose IC50 mode with 3-fold serial dilution starting at 100 μM. Curcumin is used as positive control for KAT5, MYST2/KAT7, MYST4/KAT6B, and p300, and tested in 10-dose IC50 mode with 3-fold serial dilution starting at 100 μM. Reactions are carried out at 3.08 μM Acetyl-CoA. For CBP, GCN5, MYST2/KAT7, pCAF, and p300, the substrate used is histone H3. For KAT5 and MYST4/KAT6B the substrates used are histone H2A and histone H4, respectively. Cell Assay: |
|---|---|
| In Vivo | In C57BL6 mice immunized with SRBC, GSK503 (150 mg/kg, i.p.) reduced the level of H3K27me3 in splenocytes. In male SCID mice bearing SUDHL4 and SUDHL6 tumors, GSK503 (150 mg/kg, i.p.) inhibits tumor growth. In C57Bl/6 mice bearing murine B16-F10 tumors, GSK503 (150 mg/kg, i.p.) significantly reduces global H3K27me3 levels, inhibits tumor growth and virtually abolishes metastases formation. |
| Animal model | Male SCID mice bearing SUDHL4 and SUDHL6 tumors |
| Formulation & Dosage | Dissolved in 20% captisol; 150 mg/kg; i.p. injection |
| References | Cancer Cell. 2013 May 13;23(5):677-92; Nat Commun. 2015 Jan 22;6:6051. |
