A-366

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

A-366 是一种有效的、高选择性的组蛋白甲基转移酶 G9a/GLP 抑制剂，IC50 为 3/38 nM。

A-366 is a potent, highly selective inhibitor of histone methyltransferase G9a/GLP with IC50 of 3/38 nM, >1,000-fold selectivity for G9a over 21 other methyltransferases; effects a clear reduction in H3K9 methylation in cells, shows significantly less cytotoxic effects on the growth of tumor cell lines compared to other known G9a/GLP small molecule inhibitors despite equivalent cellular activity on methylation of H3K9me2 (H3K9me2 cellular EC50=0.3 uM); induces differentiation and affects viability in MV4;11 cells, demonstrates growth inhibition in vivo consistent with the profile of H3K9me2 reduction in flank xenograft leukemia model.

A-366 (0.01-10 μM; 14 days) induces differentiation and affects viability in MV4;11 cells.A-366 (0.3-3 μM; 72 hours) reduces the total levels of H3K9me2 in a time and concentration dependent manner with a cellular EC50 of ~300 nM in PC-3 prostate adenocarcinoma cells. A-366 (0.01-10 μM; 4 days; HL-60 cells) results in a dose-dependent differentiation and a corresponding decrease in proliferation. DNA content analysis of A-366-treated HL-60 cells showed an accumulation of cells in G1 consistent with cytostasis. Cell Viability AssayCell Line:MV4;11 cells Concentration:0.01-10 μM Incubation Time:14 days Result:Resulted in inhibited proliferation and a decrease in viability corresponding to the dose response observed for CD11b staining.

A-366 (30 mg/kg; osmotic mini-pump; daily for 14 days) treatment of MV4;11 xenografts elicits growth inhibition. Animal Model:6-8 week old SCID-beige female mice (MV4;11 xenografts)Dosage:30 mg/kg Administration:By osmotic mini-pump; daily for 14 days Result:A modest 45% tumor growth inhibition resulting from A-366 treatment in this model.

A366

Chromatin/Epigenetic

HMTase

G9a/GLP

Other Indications

——

1527503-11-2

329.4366

C19H27N3O2

>98% (HPLC)

10 mM in DMSO

NC(C12CCC1)=NC3=C2C=C(OC)C(OCCCN4CCCC4)=C3

Spiro[cyclobutane-1,3'-[3H]indol]-2'-amine, 5'-methoxy-6'-[3-(1-pyrrolidinyl)propoxy]-

(-20℃)

With Ice Pack

≥ 2 years