GSK126

Short Summary : EZH2 inhibitor

Category : Stem Cell|EZH2

Purity : 0.9975

CAS Number : 1346574-57-9

Formula : C31H38N6O2

Molecular Weight : 526.67

SMILE : CCC(C)N1C=C(C2=C(C=C(C=C21)C3=CN=C(C=C3)N4CCNCC4)C(=O)NCC5=C(C=C(NC5=O)C)C)C

Solubility : >3.29mg/mL in DMSO

Storage : Store at -20°C

Description : GSK126 is an inhibitor of EZH2 with Ki Value of 93 pM [1].
Over-expression of EZH2 has been reported to be correlated with cancer progression and poor prognosis, high grade and high stage in several tumor types. GSK126 is a potent inhibitor of EZH2 and its functional residence time on activated form of EZH2/PRC2 is mush longer than unactivated forms [1]. When tested with lymphoma cell lines, results showed that harboring EZH2 mutations such as Y641N, Y641F or A677G were more sensitivity [2]. In DMS53, Lu30, H209 SCLC cells, cellular growth was inhibited with 0.5, 2, and 8M GSK126 treatment [3]. And GSK126 could also significantly restore ARNTL expression in ovarian cancer cells thus inhibit cell growth and enhance chemosensitivity of cisplatin [4].
Intermittent dosing of GSK126 treated subcutaneous KARPAS-422 xenografts model could effectively inhibit its growth with or without a 1 week drug holiday. In mouse model with EZH2 mutant DLBCL xenografts, treatment with GSK126 could markedly inhibit its growth [2].
References:1. Sato, T., et al., PRC2 overexpression and PRC2-target gene repression relating to poorer prognosis in small cell lung cancer. Sci Rep, 2013. 3(1911). 2. McCabe, M.T., et al., EZH2 inhibition as a therapeutic strategy for lymphoma with EZH2-activating mutations. Nature, 2012. 492(7427): p. 108-12. 3. Van Aller, G.S., et al., Long residence time inhibition of EZH2 in activated polycomb repressive complex 2. ACS Chem Biol, 2014. 9(3): p. 622-9. 4. Yeh, C.M., et al., Epigenetic silencing of ARNTL, a circadian gene and potential tumor suppressor in ovarian cancer. Int J Oncol, 2014. 45(5): p. 2101-7.

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