BIX-01294 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 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 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 在复发性肿瘤细胞中具有抗肿瘤活性。
生物活性 | BIX-01294 is a reversible and highly selectiveG9a and GLPHistone Methyltransferaseinhibitor, withIC50s of of 1.7 μM and 0.9 μM, respectively. BIX-01294 inhibits G9a/GLP by competing for binding with theamino acidsN-terminal of the substrate lysine residue. BIX-01294, a (1H-1,4-diazepin-1-yl)-quinazolin-4-yl amine derivative, inducesnecroptosisandautophagy. BIX-01294 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) selectively inhibits recurrent tumor cell growth[1]. BIX-01294 (1 μM) leads to a marked increase in phosphorylation of S345 of MLKL[1]. BIX-01294 (1 μM) significantly upregulates the canonical p53 targets Cdkn1a (p21) and Gadd45a in recurrent tumor cell lines[1]. BIX-01294 (1 μM; 6 days) causes the reduction in H3K9me2 levels in primary and recurrent tumor cells[1]. BIX-01294 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)[1]. BIX-01294 (4.1 μM; for 2 days) causes around a 20% reduction, concomitant with a comparable increase in the unmodified H3K9 fragment in H3K9me2 in mouse ES cells. BIX-01294 causes pronounced reduction in H3K9me2 and a small decrease for H3K9me3 and H3K9me1 in wild-type ES cells[2]. BIX-01294 has no inhibition of the other histone methyltransferases even at concentrations of 45 μM. BIX-01294 does not affect SUV39H1 (H320R) and PRMT1 within the tested concentration range (up to 10 μM)[2]. BIX-01294 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 hours | Result: | Selectively inhibited recurrent tumor cell growth. |
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体内研究 (In Vivo) | BIX-01294 (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 | Powder | -20°C | 3 years | | 4°C | 2 years | In solvent | -80°C | 6 months | | -20°C | 1 month |
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溶解性数据 | In Vitro: DMSO : ≥ 110 mg/mL(224.20 mM) H2O : 1 mg/mL(2.04 mM;Need ultrasonic) *"≥" means soluble, but saturation unknown. 配制储备液 1 mM | 2.0382 mL | 10.1908 mL | 20.3815 mL | 5 mM | 0.4076 mL | 2.0382 mL | 4.0763 mL | 10 mM | 0.2038 mL | 1.0191 mL | 2.0382 mL |
*请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液;一旦配成溶液,请分装保存,避免反复冻融造成的产品失效。 储备液的保存方式和期限:-80℃, 6 months; -20℃, 1 month。-80℃ 储存时,请在 6 个月内使用,-20℃ 储存时,请在 1 个月内使用。 In Vivo: 请根据您的实验动物和给药方式选择适当的溶解方案。以下溶解方案都请先按照In Vitro方式配制澄清的储备液,再依次添加助溶剂: ——为保证实验结果的可靠性,澄清的储备液可以根据储存条件,适当保存;体内实验的工作液,建议您现用现配,当天使用;
以下溶剂前显示的百 分比是指该溶剂在您配制终溶液中的体积占比;如在配制过程中出现沉淀、析出现象,可以通过加热和/或超声的方式助溶 1. 请依序添加每种溶剂: 10% DMSO 40%PEG300 5%Tween-80 45% saline Solubility: ≥ 2.75 mg/mL (5.60 mM); Clear solution
此方案可获得 ≥ 2.75 mg/mL (5.60 mM,饱和度未知) 的澄清溶液。 以 1 mL 工作液为例,取 100 μL 27.5 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中,混合均匀;向上述体系中加入50 μL Tween-80,混合均匀;然后继续加入 450 μL生理盐水定容至 1 mL。 2. 请依序添加每种溶剂: 10% DMSO 90% (20%SBE-β-CDin saline) Solubility: ≥ 2.75 mg/mL (5.60 mM); Clear solution
此方案可获得 ≥ 2.75 mg/mL (5.60 mM,饱和度未知) 的澄清溶液。 以 1 mL 工作液为例,取 100 μL 27.5 mg/mL 的澄清 DMSO 储备液加到 900 μL20% 的 SBE-β-CD 生理盐水水溶液中,混合均匀。 3. 请依序添加每种溶剂: 10% DMSO 90%corn oil Solubility: ≥ 2.75 mg/mL (5.60 mM); Clear solution
此方案可获得 ≥ 2.75 mg/mL (5.60 mM,饱和度未知) 的澄清溶液,此方案不适用于实验周期在半个月以上的实验。 以 1 mL 工作液为例,取 100 μL 27.5 mg/mL 的澄清 DMSO 储备液加到 900 μL玉米油中,混合均匀。 *以上所有助溶剂都可在本网站选购。
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