BIX 01294 Trihydrochloride

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

BIX01294 是一种 G9a 组蛋白甲基转移酶抑制剂，在无细胞测定中 IC50 为 2.7 μM。

BIX01294 is an inhibitor of G9a histone methyltransferase with IC50 of 2.7 μM in a cell-free assay, reduces H3K9me2 of bulk histones, also weakly inhibits GLP (primarily H3K9me3), no significant activity observed at other histone methyltransferases.

BIX-01294 (2 μM; 48 h) trihydrochloride selectively inhibits recurrent tumor cell growth. BIX-01294 (1 μM) trihydrochloride leads to a marked increase in phosphorylation of S345 of MLKL. BIX-01294 (1 μM) trihydrochloride significantly upregulates the canonical p53 targets Cdkn1a (p21) and Gadd45a in recurrent tumor cell lines. BIX-01294 (1 μM; 6 days) trihydrochloride causes the reduction in H3K9me2 levels in primary and recurrent tumor cells. BIX-01294 trihydrochloride leads to necroptotic cell death in recurrent tumor cells. Necrostatin-1 (30 μM) partially reverses cell death induced by BIX-01294 (750 nM; 24 h) trihydrochloride. BIX-01294 (4.1 μM; for 2 days) trihydrochloride causes around a 20% reduction, concomitant with a comparable increase in the unmodified H3K9 fragment in H3K9me2 in mouse ES cells. BIX-01294 trihydrochloride causes pronounced reduction in H3K9me2 and a small decrease for H3K9me3 and H3K9me1 in wild-type ES cells. BIX-01294 trihydrochloride has no inhibition of the other histone methyltransferases even at concentrations of 45 μM. BIX-01294 trihydrochloride does not affect SUV39H1 (H320R) and PRMT1 within the tested concentration range (up to 10 μM).BIX-01294 trihydrochloride inhibits G9a in an uncompetitive manner with S-adenosyl-methionine (SAM). BIX-01294 (1 μg/mL) causes reduction in the BrdU incorporation of fetal PASMCs. BIX-01294 treatment decreases the PASMCs migration induced by PDGF. Cell Viability AssayCell Line:Primary or recurrent tumor cells. Concentration:2 μM Incubation Time:48 hResult:Selectively inhibited recurrent tumor cell growth.

BIX-01294 trihydrochloride (10 mg/kg; IP; three times a week for 2 weeks) significantly reduces tumor growth and tumor burden in recurrent tumor cells. Primary tumor growth is not inhibited. Animal Model:Female MMTV-rtTA;TetO-Her2/neu (MTB;TAN) and TetO-Her2/neu (TAN) mice with recurrent or primary tumor cells Dosage:10 mg/kg Administration:IP; three times a week for 2 weeks Result:Significantly reduced tumor growth and tumor burden in recurrent tumor cells. Primary tumor growth was not inhibited. Slowed the growth of orthotopic recurrent tumors in athymic nude recipients.

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Chromatin/Epigenetic

HMTase

G9a

Other Indications

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1392399-03-9

600.02

C28H38N6O2·3HCl

>98% (HPLC)

Ethanol: 8 mg/mL (13.33 mM); Water: 98 mg/mL (163.32 mM); DMSO: 98 mg/mL (163.32 mM)

Cl.Cl.Cl.COC1=C(OC)C=C2C(NC3CCN(CC4=CC=CC=C4)CC3)=NC(=NC2=C1)N1CCCN(C)CC1

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(-20℃)

With Ice Pack

≥ 2 years