GSK503

SKU: orb1226484

Description

GSK503 is a potent, specific EZH2 methyltransferase inhibitor that inhibits the methyltransferase activity of WT and mutant EZH2 with similar potency (Ki app=3-27 nM); GSK503 is highly selective for the SET domain of EZH2, >200 fold selective over EZH1 and > 4000 fold selective over other HMTases; inhibits GCB lymphoma cell lines with IC50 of 0.5-20 uM; impairs proliferation and invasiveness, accompanied by re-expression of tumour suppressor in melanoma cells; stabilizes the disease through inhibition of growth and virtually abolishes metastases formation without affecting normal melanocyte biology in melanoma mouse model.

Key Properties

• CAS Number: 1346572-63-1
• MW: 526.6724
• Purity: >98% (HPLC)
• Formula: C₃₁H₃₈N₆O₂
• SMILES: O=C(C1=CC(C2=CC=C(N3CCN(C)CC3)N=C2)=CC4=C1C(C)=CN4C(C)C)NCC5=C(C)C=C(C)NC5=O
• Target: HMTase
• Solubility: DMSO: ≥ 44 mg/mL

Bioactivity

• In Vivo:
  In a melanoma mouse model, conditional EZH2 ablation as much as treatment with the GSK503 stabilizes the disease through inhibition of growth and virtually abolishes metastases formation without affecting normal melanocyte biology. GSK503 displays favorable pharmacokinetics in mice. GSK503, but not vehicle, prevents the formation of germinal center after SRBC or NP-KLH immunization, phenocopying the Ezh2 null phenotype. GSK503 treatment leads to reduced numbers of GC B-cells by flow cytometry, reduces number and volume of GCs by immunohistochemistry, and impairs formation high affinity antibodies.
• In Vitro:
  GSK503 inhibits the methyltransferase activity of wild type and mutant EZH2 with similar potency (Kiapp=3-27 nM) and is structurally related to GSK126 and GSK343. GSK503 is >200 fold selective over EZH1 (Kiapp=636 nM) and >4000 fold selective over other histone methyltransferases.

Storage & Handling

• Storage: Storage temperature: -20°C. Stability: ≥ 2 years
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

GSK-503

Quick Database Links

Gene Symbol

HMTase