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地西司他：一种用于治疗慢性肾脏病所致贫血的新型脯氨酰羟化酶抑制剂。

Desidustat: a novel PHD inhibitor for the treatment of CKD-induced anemia.

作者信息

Joharapurkar Amit, Pandya Vrajesh, Patel Harilal, Jain Mukul, Desai Ranjit

机构信息

Zydus Research Centre, Zydus Lifesciences Limited, Ahmedabad, Gujarat, India.

出版信息

Front Nephrol. 2024 Oct 22;4:1459425. doi: 10.3389/fneph.2024.1459425. eCollection 2024.

DOI:10.3389/fneph.2024.1459425
PMID:39502472
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11534831/
Abstract

Desidustat is a small molecule inhibitor of hypoxia-inducible factor-prolyl hydroxylase (HIF-PH) discovered and developed by Zydus Lifesciences for the treatment of anemia associated with chronic kidney disease (CKD). This review summarizes the preclinical and clinical profile of desidustat which led to its approval and clinical use in India.

摘要

地西司他是一种小分子低氧诱导因子脯氨酰羟化酶（HIF-PH）抑制剂，由Zydus生命科学公司发现并开发，用于治疗与慢性肾脏病（CKD）相关的贫血。本综述总结了地西司他的临床前和临床概况，这些概况促成了其在印度的获批和临床应用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3cc8/11534831/3c479b278c01/fneph-04-1459425-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3cc8/11534831/3c479b278c01/fneph-04-1459425-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3cc8/11534831/3c479b278c01/fneph-04-1459425-g001.jpg

相似文献

1
Desidustat: a novel PHD inhibitor for the treatment of CKD-induced anemia.地西司他：一种用于治疗慢性肾脏病所致贫血的新型脯氨酰羟化酶抑制剂。
Front Nephrol. 2024 Oct 22;4:1459425. doi: 10.3389/fneph.2024.1459425. eCollection 2024.
2
Desidustat: First Approval.地舒单抗：首次获批
Drugs. 2022 Jul;82(11):1207-1212. doi: 10.1007/s40265-022-01744-w.
3
Prolyl hydroxylase inhibitor desidustat protects against acute and chronic kidney injury by reducing inflammatory cytokines and oxidative stress.脯氨酰羟化酶抑制剂地舒单抗通过减少炎症细胞因子和氧化应激来预防急性和慢性肾损伤。
Drug Dev Res. 2021 Sep;82(6):852-860. doi: 10.1002/ddr.21792. Epub 2021 Jan 22.
4
Prolyl hydroxylase inhibitor desidustat improves anemia in erythropoietin hyporesponsive state.脯氨酰羟化酶抑制剂地西司他在促红细胞生成素低反应状态下可改善贫血。
Curr Res Pharmacol Drug Discov. 2022 Apr 30;3:100102. doi: 10.1016/j.crphar.2022.100102. eCollection 2022.
5
HIF-PHD inhibitor desidustat ameliorates iron deficiency anemia.缺氧诱导因子脯氨酰羟化酶抑制剂地西司他改善缺铁性贫血。
Toxicol Appl Pharmacol. 2024 Feb;483:116832. doi: 10.1016/j.taap.2024.116832. Epub 2024 Jan 22.
6
Long-term efficacy and safety of hypoxia-inducible factor prolyl hydroxylase inhibitors in anaemia of chronic kidney disease: A meta-analysis including 13,146 patients.缺氧诱导因子脯氨酰羟化酶抑制剂治疗慢性肾脏病贫血的长期疗效和安全性：一项包含 13146 名患者的荟萃分析。
J Clin Pharm Ther. 2021 Aug;46(4):999-1009. doi: 10.1111/jcpt.13385. Epub 2021 Feb 21.
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Desidustat in Anemia due to Dialysis-Dependent Chronic Kidney Disease: A Phase 3 Study (DREAM-D).地舒单抗治疗透析依赖性慢性肾脏病所致贫血的 3 期研究（DREAM-D）。
Am J Nephrol. 2022;53(5):343-351. doi: 10.1159/000523949. Epub 2022 Apr 22.
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Effects of hypoxia-inducible factor-prolyl hydroxylase inhibitors . erythropoiesis-stimulating agents on iron metabolism in non-dialysis-dependent anemic patients with CKD: A network meta-analysis.低氧诱导因子脯氨酰羟化酶抑制剂和促红细胞生成刺激剂对非透析依赖性 CKD 贫血患者铁代谢的影响：网状 Meta 分析。
Front Endocrinol (Lausanne). 2023 Mar 16;14:1131516. doi: 10.3389/fendo.2023.1131516. eCollection 2023.
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Desidustat in Anemia due to Non-Dialysis-Dependent Chronic Kidney Disease: A Phase 3 Study (DREAM-ND).非透析依赖性慢性肾脏病所致贫血的地舒单抗治疗 3 期研究（DREAM-ND）。
Am J Nephrol. 2022;53(5):352-360. doi: 10.1159/000523961. Epub 2022 Apr 22.
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Crystallographic and Selectivity Studies on the Approved HIF Prolyl Hydroxylase Inhibitors Desidustat and Enarodustat.已获批的低氧诱导因子脯氨酰羟化酶抑制剂地西他司他和依那司他的晶体学及选择性研究
ChemMedChem. 2024 Dec 16;19(24):e202400504. doi: 10.1002/cmdc.202400504. Epub 2024 Nov 8.

引用本文的文献

1
Derivatives of the Clinically Used HIF Prolyl Hydroxylase Inhibitor Desidustat Are Efficient Inhibitors of Human γ-Butyrobetaine Hydroxylase.临床使用的低氧诱导因子脯氨酰羟化酶抑制剂地西司他的衍生物是人类γ-丁甜菜碱羟化酶的有效抑制剂。
J Med Chem. 2025 May 8;68(9):9777-9798. doi: 10.1021/acs.jmedchem.5c00586. Epub 2025 Apr 22.
2
Prolyl hydroxylase inhibitor desidustat improves stroke outcomes via enhancing efferocytosis in mice with chronic kidney disease.脯氨酰羟化酶抑制剂地西司他通过增强慢性肾病小鼠的胞葬作用改善中风预后。
Exp Neurol. 2025 Apr;386:115181. doi: 10.1016/j.expneurol.2025.115181. Epub 2025 Feb 4.

本文引用的文献

1
HIF Stabilizer Desidustat Protects against Complement-Mediated Diseases.HIF 稳定剂地拉罗司（desidustat）可预防补体介导的疾病。
Drug Res (Stuttg). 2024 Sep;74(7):325-334. doi: 10.1055/a-2347-9919. Epub 2024 Jul 11.
2
A Case of Erythropoietin (EPO)-Induced Pure Red Cell Aplasia and Its Treatment Efficacy With Desidustat.一例促红细胞生成素（EPO）诱导的纯红细胞再生障碍性贫血病例及其使用地西司他的治疗效果
Cureus. 2024 Jun 9;16(6):e62022. doi: 10.7759/cureus.62022. eCollection 2024 Jun.
3
Growing concerns about using hypoxia-inducible factor prolyl hydroxylase inhibitors for the treatment of renal anemia.
对使用缺氧诱导因子脯氨酰羟化酶抑制剂治疗肾性贫血的担忧日益增加。
Clin Kidney J. 2024 Feb 28;17(3):sfae051. doi: 10.1093/ckj/sfae051. eCollection 2024 Mar.
4
Novel anemia therapies in chronic kidney disease: conclusions from a Kidney Disease: Improving Global Outcomes (KDIGO) Controversies Conference.慢性肾脏病新型贫血治疗方法：改善全球肾脏病预后组织（KDIGO）争议会议的结论。
Kidney Int. 2023 Oct;104(4):655-680. doi: 10.1016/j.kint.2023.05.009. Epub 2023 May 24.
5
Hypoxia-Inducible Factor 1-Alpha and Glucose Metabolism during Cardiac Remodeling Progression from Hypertrophy to Heart Failure.低氧诱导因子 1-α与葡萄糖代谢在心脏重构从肥厚到心力衰竭进展中的作用。
Int J Mol Sci. 2023 Mar 25;24(7):6201. doi: 10.3390/ijms24076201.
6
Roxadustat and its failure: A comparative dynamic study.罗沙司他及其失败：一项比较动态研究。
J Mol Graph Model. 2023 May;120:108422. doi: 10.1016/j.jmgm.2023.108422. Epub 2023 Jan 21.
7
Preclinical Characterization of Vadadustat (AKB-6548), an Oral Small Molecule Hypoxia-Inducible Factor Prolyl-4-Hydroxylase Inhibitor, for the Potential Treatment of Renal Anemia.口服小分子缺氧诱导因子脯氨酰-4-羟化酶抑制剂瓦达司他（AKB-6548）用于潜在治疗肾性贫血的临床前特征研究
J Pharmacol Exp Ther. 2022 Oct;383(1):11-24. doi: 10.1124/jpet.122.001126. Epub 2022 Aug 4.
8
Nonclinical Pharmacokinetic Evaluation of Desidustat: a Novel Prolyl Hydroxylase Inhibitor for the Treatment of Anemia.地舒单抗的非临床药代动力学评价：一种新型脯氨酰羟化酶抑制剂，用于治疗贫血。
Eur J Drug Metab Pharmacokinet. 2022 Sep;47(5):725-740. doi: 10.1007/s13318-022-00788-3. Epub 2022 Jul 26.
9
Desidustat: First Approval.地舒单抗：首次获批
Drugs. 2022 Jul;82(11):1207-1212. doi: 10.1007/s40265-022-01744-w.
10
HIF-PHIs for Anemia Management in CKD: Potential and Uncertainty ASCEND.用于慢性肾脏病贫血管理的低氧诱导因子脯氨酰羟化酶抑制剂：潜力与不确定性——ASCEND研究
Clin J Am Soc Nephrol. 2022 Aug;17(8):1255-1258. doi: 10.2215/CJN.02440222. Epub 2022 Jul 5.