BIX-01294 trihydrochloride 是一种可逆且高度选择性的G9a和GLP组蛋白甲基转移酶抑制剂，IC50分别为 1.9 μM 和 0.7 μM。BIX-01294 trihydrochloride 通过与底物赖氨酸残基 N 端的氨基酸竞争结合来抑制 G9a/GLP。BIX-01294 trihydrochloride 是一种 (1H-1,4-diazepin-1-yl)-quinazolin-4-yl 胺衍生物，可诱导坏死性凋亡 (necroptosis) 和自噬。BIX-01294 trihydrochloride 在复发性肿瘤细胞中具有抗肿瘤活性。
| 生物活性 | BIX-01294 trihydrochloride is a reversible and highly selectiveG9a and GLPHistone Methyltransferaseinhibitor, withIC50s of of 1.7 μM and 0.9 μM, respectively. BIX-01294 trihydrochloride inhibits G9a/GLP by competing for binding with theamino acidsN-terminal of the substrate lysine residue. BIX-01294 trihydrochloride, a (1H-1,4-diazepin-1-yl)-quinazolin-4-yl amine derivative, inducesnecroptosisandautophagy. BIX-01294 trihydrochloride has antitumor activity in recurrent tumor cells[1][2][3][4][5]. |
| IC50& Target | IC50: 2.7 μM (G9a in DELFIA assay)[2]
IC50: 1.9 μM for G9a and 0.7 μM for GLP[5] |
体外研究
(In Vitro) | BIX-01294 (2 μM; 48 h) trihydrochloride selectively inhibits recurrent tumor cell growth[1].
BIX-01294 (1 μM) trihydrochloride leads to a marked increase in phosphorylation of S345 of MLKL[1].
BIX-01294 (1 μM) trihydrochloride significantly upregulates the canonical p53 targets Cdkn1a (p21) and Gadd45a in recurrent tumor cell lines[1].
BIX-01294 (1 μM; 6 days) trihydrochloride causes the reduction in H3K9me2 levels in primary and recurrent tumor cells[1].
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[1].
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[2].
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)[2].
BIX-01294 trihydrochloride inhibits G9a in an uncompetitive manner with S-adenosyl-methionine (SAM)[2].
BIX-01294 (1 μg/mL) causes reduction in the BrdU incorporation of fetal PASMCs. BIX-01294 treatment decreases the PASMCs migration induced by PDGF[3].
Cell Viability Assay[1] | Cell Line: | Primary or recurrent tumor cells | | Concentration: | 2 μM | | Incubation Time: | 48 h | | Result: | Selectively inhibited recurrent tumor cell growth. |
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体内研究
(In Vivo) | 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[1].
| Animal Model: | Female MMTV-rtTA;TetO-Her2/neu (MTB;TAN) and TetO-Her2/neu (TAN) mice with recurrent or primary tumor cells[1] | | 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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| 运输条件 | Room temperature in continental US; may vary elsewhere. |
| 储存方式 | Please store the product under the recommended conditions in the Certificate of Analysis. |
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