Furamidine dihydrochloride (DB75 dihydrochloride) 是一种选择性的且细胞可渗透的蛋白精氨酸甲基转移酶 1 (PRMT1) 抑制剂,IC50为 9.4 μM。Furamidine dihydrochloride 对PRMT1的选择性高于 PRMT5,PRMT6 和 PRMT4 (CARM1) (IC50分别为 166 μM,283 μM 和 >400 μM)。Furamidine dihydrochloride 是一种有效的,可逆的和竞争性的酪氨酰 DNA 磷酸二酯酶 1 (TDP-1) 抑制剂。Furamidine dihydrochloride 对TDP-1的抑制作用对单链和双链 DNA 底物均有效,对双链 DNA 的作用更强。Furamidine dihydrochloride 也是一种抗寄生虫剂。
生物活性 | Furamidine dihydrochloride (DB75 dihydrochloride) is a selectiveprotein arginine methyltransferase 1 (PRMT1)inhibitor with anIC50of 9.4 μM. Furamidine dihydrochloride is selective forPRMT1overPRMT5,PRMT6, andPRMT4(CARM1) (IC50s of 166 μM, 283 μM, and >400 μM, respectively). Furamidine dihydrochloride is a potent, reversible and competitivetyrosyl-DNAphosphodiesterase1 (TDP-1)inhibitor. Inhibition ofTDP-1by Furamidine dihydrochloride is effective both with single- and double-stranded DNA substrates but is slightly stronger with the duplex DNA. Furamidine dihydrochloride is also an antiparasite agent[1][2][3]. |
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体外研究 (In Vitro) | Furamidine (compound 1; 20 μM; 72 hours; leukemia cell lines) inhibits cell growth for most of the leukemia cell lines except HEL cells which have JAK2V617F mutations[1]. Furamidine (compound 1; 20 μM; 15 hours; 293T cells) treatment significantly reduces the expression level of the methylated GFP-ALY protein in 293T cells[1]. Furamidine binds duplex DNA in the DNA minor groove selectively at AT rich sites [(A/T)4]. Furamidine can also intercalate between GC base pairs of duplex DNA. Furamidine could therefore interfere with DNA processing enzymes such as TDP-1[2].
Cell Viability Assay[1] Cell Line: | Meg-01, K562, HL-60, NB4, MOLM13, HEL, CMK, CMY, CMS and CHRF cells | Concentration: | 20 μM | Incubation Time: | 72 hours | Result: | Inhibited cell growth for most of the leukemia cell lines except HEL cells which have JAK2V617F mutations. |
Western Blot Analysis[1] Cell Line: | 293T cells | Concentration: | 20 μM | Incubation Time: | 15 hours | Result: | The expression level of the methylated GFP-ALY protein is significantly reduced. |
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体内研究 (In Vivo) | Furamidine (1 mg/kg; intraperitoneal injection; 3 times a week and repeated every 4 weeks; for 34 weeks; female NZB/NZW mice) and Irinotecan combined treatment suppresses proteinuria and prolongs survival of lupus-prone NZB/NZW mice. The combination treatment does not change the levels of anti-dsDNA antibodies[3].
Animal Model: | Female NZB/NZW mice (6-week-old) with Irinotecan (1 mg/kg)[3] | Dosage: | 1 mg/kg | Administration: | Intraperitoneal injection; 3 times a week and repeated every 4 weeks; for 34 weeks | Result: | Suppressed proteinuria and prolongs survival of lupus-prone NZB/NZW mice combined with Irinotecan. |
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运输条件 | Room temperature in continental US; may vary elsewhere. |
储存方式 | -20°C, sealed storage, away from moisture *In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture) |
溶解性数据 | In Vitro: DMSO : 12.5 mg/mL(33.13 mM;Need ultrasonic) 配制储备液 1 mM | 2.6506 mL | 13.2531 mL | 26.5062 mL | 5 mM | 0.5301 mL | 2.6506 mL | 5.3012 mL | 10 mM | 0.2651 mL | 1.3253 mL | 2.6506 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 (sealed storage, away from moisture)。-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: ≥ 1.25 mg/mL (3.31 mM); Clear solution
此方案可获得 ≥ 1.25 mg/mL (3.31 mM,饱和度未知) 的澄清溶液。 以 1 mL 工作液为例,取 100 μL 12.5 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%corn oil Solubility: ≥ 1.25 mg/mL (3.31 mM); Clear solution
此方案可获得 ≥ 1.25 mg/mL (3.31 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 12.5 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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