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Daprodustat(GSK1278863)
本产品不向个人销售,仅用作科学研究,不用于任何人体实验及非科研性质的动物实验。
Daprodustat(GSK1278863)图片
CAS NO:960539-70-2
包装与价格:
包装价格(元)
5mg电议
10mg电议
50mg电议
100mg电议

产品介绍
Daprodustat(GSK1278863) (GSK1278863) 是一种口服活性缺氧诱导因子脯氨酰羟化酶 (HIF-PH) 抑制剂,正在开发用于治疗与慢性肾病相关的贫血。
Cas No.960539-70-2
别名达普司他,GSK1278863
化学名2-(1,3-dicyclohexyl-2,4,6-trioxohexahydropyrimidine-5-carboxamido)acetic acid
Canonical SMILESO=C(O)CNC(C(C(N1C2CCCCC2)=O)C(N(C1=O)C3CCCCC3)=O)=O
分子式C19H27N3O6
分子量393.43
溶解度≥ 7.86mg/mL in DMSO with gentle warming
储存条件Store at -20℃
General tipsFor obtaining a higher solubility , please warm the tube at 37 ℃ and shake it in the ultrasonic bath for a while.
Shipping ConditionEvaluation sample solution : ship with blue ice
All other available size: ship with RT , or blue ice upon request
产品描述

Daprodustat (GSK1278863) is a HIF-prolyl hydroxylase inhibitor.

Hypoxia stimulates erythropoietin (EPO) release through accumulation of hypoxia-inducible factor 1α (HIF-1α), resulting in an increase of erythrocyte production by the bone marrow. HIF-prolyl hydroxylase inhibitors have been used to selectively activate the PHD-signaling pathway, leading to the stabilization of HIFα subunits, which can affect the transcription of HIF-responsive genes.

In vitro: In-vitro biotransformation data indicated that GSK1278863 was primarily metabolized by CYP2C8 [1].

In vivo: Currently, there is no animal in vivo data published.

Clinical trial: Previous study found that in both Japanese and Caucasian subjects GSK1278863 showed dose-proportional increases in AUCinf, with a 1.3-1.5-fold higher exposure seen in Japanese relative to Caucasians. Such exposure difference could be mainly explained by the observed differences in body weights. Statistically significant increases in erythropoietin, vascular endothelial growth factor (VEGF) and reticulocyte counts were observed in Japanese subjects as compared to placebo. In Caucasians, erythropoietin and VEGF levels were increased in response to the 100 mg dose. Moreover, drug-related adverse events, sucha as headache and abdominal pain, were reported in three Japanese subjects, whereas, headache was reported in three Caucasians [1]. A 28-day, phase 2A, randomized trial showed that GSK1278863 induced an effective EPO response and stimulated non-EPO mechanisms for erythropoiesis in anemic non-dialysis-dependent and dialysis-dependent patients with CKD [2].

References:
[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.