Daprodustat(GSK1278863)
mRNA synthesis
In vitro transcription of capped mRNA with modified nucleotides and Poly(A) tail
Tyramide Signal Amplification (TSA)
TSA (Tyramide Signal Amplification), used for signal amplification of ISH, IHC and IC etc.
Phos Binding Reagent Acrylamide
Separation of phosphorylated and non-phosphorylated proteins without phospho-specific antibody
Cell Counting Kit-8 (CCK-8)
A convenient and sensitive way for cell proliferation assay and cytotoxicity assay
SYBR Safe DNA Gel Stain
Safe and sensitive stain for visualization of DNA or RNA in agarose or acrylamide gels.
Inhibitor Cocktails
Protect the integrity of proteins from multiple proteases and phosphatases for different applications.
Daprodustat(GSK1278863)是一种HIF-脯氨酰羟化酶抑制剂。
缺氧通过缺氧诱导因子1α(HIF-1α)的积累刺激促红细胞生成素(EPO)释放,导致骨髓产生的红细胞增加。HIF-脯氨酰羟化酶抑制剂已被用于选择性地激活PHD信号传导途径,导致可以影响HIF应答基因转录的HIFα亚基的稳定。
体外:体外生物转化数据表明,GSK1278863主要通过CYP2C8代谢[1]。
体内:目前尚无动物体内数据公布。
临床试验:先前研究发现, GSK1278863在日本和白种人中都表现出AUCinf的剂量成比例增加,相对于白种人,在日本人中观察到高1.3-1.5倍的暴露。这种暴露差异主要可通过观察到的体重差异来解释。与安慰剂相比,在日本受试者中观察到红细胞生成素、血管内皮生长因子(VEGF)和网织红细胞计数统计学显著增加。在白种人中,应答100 mg剂量的促红细胞生成素和VEGF水平增加。此外,在三个日本受试者中出现药物相关的不良事件,例如头痛和腹痛,而在三个白种人受试者中出现头痛[1]。 一项28天的2A期随机试验显示,在非透析依赖性和透析依赖性的贫血CKD患者中,GSK1278863诱导有效的EPO应答,刺激红细胞生成的非EPO机制[2]。
参考文献:
[1] Hara K,Takahashi N,Wakamatsu A,Caltabiano S. Pharmacokinetics, pharmacodynamics and safety of single, oral doses of GSK1278863, a novel HIF-prolyl hydroxylase inhibitor, in healthy Japanese and Caucasian subjects. Drug Metab Pharmacokinet.2015 Dec;30(6):410-8.
[2] Brigandi RA,Johnson B,Oei C,et al. A Novel Hypoxia-Inducible Factor-Prolyl Hydroxylase Inhibitor (GSK1278863) for Anemia in CKD: A 28-Day, Phase 2A Randomized Trial. Am J Kidney Dis.2016 Jun;67(6):861-71.
Physical Appearance | A solid |
Storage | Store at -20°C |
M.Wt | 393.43 |
Cas No. | 960539-70-2 |
Formula | C19H27N3O6 |
Solubility | insoluble in EtOH; insoluble in H2O; ≥7.86 mg/mL in DMSO with gentle warming |
Chemical Name | 2-(1,3-dicyclohexyl-2,4,6-trioxohexahydropyrimidine-5-carboxamido)acetic acid |
SDF | Download SDF |
Canonical SMILES | O=C(O)CNC(C(C(N1C2CCCCC2)=O)C(N(C1=O)C3CCCCC3)=O)=O |
运输条件 | 蓝冰运输或根据您的需求运输。 |
一般建议 | 不同厂家不同批次产品溶解度各有差异,仅做参考。若实验所需浓度过大至产品溶解极限,请添加助溶剂助溶或自行调整浓度。溶液形式一般不宜长期储存,请尽快用完。 |
质量控制和MSDS
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