常山酮溴酸盐作用机制- Medchemexpress- MCE中国

Product Data?SheetHalofuginone hydrobromideCat. No.:CAS No.:分?式:分?量:作?靶点:作?通路:储存?式:HY-N1584A64924-67-0C??H??Br?ClN?O?495.59DNA/RNA Synthesis; TGF-beta/Smad; ParasiteCell Cycle/DNA Damage; Stem Cell/Wnt; TGF-beta/Smad; Anti-infectionPowderIn solvent-20°C4°C-80°C-20°C3 years2 years6 months1 monthInhibitors?Agonists?Screening Libraries溶解性数据体外实验DMSO : 50 mg/mL (100.89 mM; Need ultrasonic)Mass1 mg5 mg10 mgSolventConcentration制备储备液1 mM5 mM10 mM2.0178 mL0.4036 mL0.2018 mL10.0890 mL2.0178 mL1.0089 mL20.1780 mL4.0356 mL2.0178 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；?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?式和期限：-80°C, 6 months; -20°C, 1 month。-80°C 储存时，请在 6 个?内使?，-20°C 储存时，请在 1 个?内使?。体内实验请根据您的实验动物和给药?式选择适当的溶解?案。以下溶解?案都请先按照 In Vitro ?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?作液，建议您现?现配，当天使?； 以下溶剂前显?的百分?是指该溶剂在您配制终溶液中的体积占?；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?式助溶1. 请依序添加每种溶剂：?10% DMSO ?? 40% PEG300 ?? 5% Tween-80 ?? 45% salineSolubility: ≥ 2.5 mg/mL (5.04 mM); Clear solution此?案可获得 ≥ 2.5 mg/mL (5.04 mM，饱和度未知) 的澄清溶液。 以 1 mL ?作液为例，取 100 μL 25.0 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? 50 μL Tween-80，混合均匀；然后继续加? 450 μL ?理盐?定容? 1 mL。2. 请依序添加每种溶剂：?10% DMSO ?? 90% (20% SBE-β-CD in saline)Solubility: ≥ 2.5 mg/mL (5.04 mM); Clear solution此?案可获得 ≥ 2.5 mg/mL (5.04 mM，饱和度未知) 的澄清溶液。 Page 1 of 2 www.MedChemExpress.cn

以 1 mL ?作液为例，取 100 μL 25.0 mg/mL 的澄清 DMSO 储备液加到 900 μL 20% 的 SBE-β-CD ?理盐??溶液中，混合均匀。3. 请依序添加每种溶剂：?10% DMSO ?? 90% corn oilSolubility: ≥ 2.5 mg/mL (5.04 mM); Clear solution此?案可获得 ≥ 2.5 mg/mL (5.04 mM，饱和度未知) 的澄清溶液，此?案不适?于实验周期在半个?以上的实验。 以 1 mL ?作液为例，取 100 μL 25.0 mg/mL 的澄清 DMSO 储备液加到 900 μL ??油中，混合均匀。BIOLOGICAL ACTIVITY?物活性Halofuginone hydrobromide (RU-19110 hydrobromide) 是 Febrifugine 的?种低毒性衍?物，可从 Dichroa febrifuga 中分离出来[1]。Halofuginone 是?种 ATP 竞争性的脯氨酰-tRNA 合成酶 (prolyl-tRNA synthetase) 抑制剂，Ki 为 18.3 nM[2]。Halofuginone 通过抑制 TGF-β 活性可减轻?关节炎[3]。IC?? & Target体外研究Ki: 18.3±0.5 nM (prolyl-tRNA synthetase)[2]Halofuginone competitively inhibits prolyl-tRNA synthetase by occupying both the prolineand tRNA-binding pockets of prolyl-tRNA synthetase[1]. The IC50s of Halofuginone (1, 10, 100, 1000, 10000 nM; 48 hours) are 114.6 and 58.9 nM in KYSE70 and A549 cells, respectively. The IC50s of Halofuginone (1, 10, 100, 1000 nM; 24 hours) for NRF2 protein are 22.3 and 37.2 nM in KYSE70 and A549 cells, respectively. The IC50 of Halofuginone for global protein synthesis is 22.6 and 45.7 nM in KYSE70 and A549 cells, respectively[1]. Cell Viability Assay[1]Cell Line:KYSE70 cells from human oesophageal cancer harbouring a mutation in the NRF2 gene and A549 cells harbouring theKEAP1 gene mutationConcentration:Incubation Time:Result:Western Blot Analysis[1]Cell Line:KYSE70 cells from human oesophageal cancer harbouring a mutation in the NRF2 gene and A549 cells harbouring theKEAP1 gene mutation.Concentration:Incubation Time:Result:1, 10, 100, 1000 nM24 hoursThe IC50s for NRF2 protein were 22.3 and 37.2 nM in KYSE70 and A549 cells, respectively.1, 10, 100, 1000, 10000 nM48 hoursThe IC50s were 114.6 and 58.9 nM in KYSE70 and A549 cells, respectively.体内研究Halofuginone (0.2, 0.5, 1 or 2.5 mg/kg; injected intraperitoneally every other day for 1 month) attenuates progression of OA in anterior cruciate ligament transection (ACLT) mice. Lower concentration (0.2 or 0.5 mg/kg) has minimal effects on subchondral bone and higher concentration (2.5 mg/kg) induces proteoglycan loss in articular cartilage[3]. Halofuginone (0.25 mg/kg; intraperitoneally injected; every day; 16 days) decreases NRF2 protein levels in tumors. While the tumor volumes do not change substantially between treatments with the vehicle, Halofuginone (0.25 Page 2 of 3 www.MedChemExpress.cn

mg/kg, intraperitoneally injected, every day) or cisplatin alone. Combined treatment with Halofuginone and Cisplatin significantly suppresses the tumor volume compared to treatment with Halofuginone or cisplatin alone[1]. Animal Model:Dosage:Administration:Result:3-month-old male C57BL/6J (WT) mice[3]0.2, 0.5, 1 or 2.5 mg/kgInjected intraperitoneally every other day for 1 monthAttenuated progression of OA in ACLT mice.Animal Model:Dosage:Administration:Result:Male nude mice (BALB/C nu/nu mice) (6-8-week)[1]0.25 mg/kgIntraperitoneally injected; every day; 16 daysThe combined treatment with Cisplatin significantly suppressed the tumor volume. NRF2 protein levels in tumors were indeed decreased.REFERENCES[1].?Tsuchida K, et al. Halofuginone enhances the chemo-sensitivity of cancer cells by suppressing NRF2 accumulation. Free Radic Biol Med. 2017 Feb;103:236-247.[2].?Keller TL, et al. Halofuginone and other Febrifugine derivatives inhibit prolyl-tRNA synthetase. Nat Chem Biol. 2012 Feb 12;8(3):311-7.[3].?Cui Z, et al. Halofuginone attenuates osteoarthritis by inhibition of TGF-β activity and H-type vessel formation in subchondral bone. Ann Rheum Dis. 2016 Sep;75(9):1714-21.McePdfHeightCaution: Product has not been fully validated for medical applications. For research use only.

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