GSK503

本公司产品仅用于科研实验，不得用于人体或动物的临床与诊断

GSK503 是一种有效的、特异性的 EZH2 甲基转移酶抑制剂，可抑制 WT 和突变型 EZH2 的甲基转移酶活性，具有相似的效力 (Ki app=3-27 nM)。

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.

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.

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.

GSK-503

Chromatin/Epigenetic

HMTase

EZH2

Cancer

——

1346572-63-1

526.6724

C31H38N6O2

>98% (HPLC)

DMSO: ≥ 44 mg/mL

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

1H-Indole-4-carboxamide, N-[(1,2-dihydro-4,6-dimethyl-2-oxo-3-pyridinyl)methyl]-3-methyl-1-(1-methylethyl)-6-[6-(4-methyl-1-piperazinyl)-3-pyridinyl]-

(-20℃)

With Ice Pack

≥ 2 years