Delving into the Latest Updates on Enarodustat with Synapse

The CANNON trial is a prospective, open-label, randomized, multicenter study designed to investigate rational hemoglobin target value in patients with anemia of non-dialysis chronic kidney disease treated with enarodustat. Eligible patients are randomly assigned 1:1 to the high-hemoglobin target group （hemoglobin of 13 g/dl）and low-hemoglobin target group （hemoglobin of 11 g/dl）and administered with enarodustat to achieve and maintain target hemoglobin over 96 weeks. The first primary endpoint was the difference of mean change in 36-Item Short Form Health Survey at week 24. The second primary endpoint was safety endpoints included time to major adverse cardiovascular + event (MACE+; all-cause mortality, myocardial infarction, stroke, and congestive heart failure requiring hospitalization) during 96 weeks.

Start Date01 Dec 2024

Sponsor / Collaborator

Zhongshan Hospital Fudan University

[+1]

NCT06737081

/ RecruitingPhase 2

A Parallel, Open-label Phase II Clinical Study of Enarodustat (SAL-0951) Tablets in the Treatment of Chemotherapy-induced Anemia in Patients With Non-myeloid Malignancies

The purpose of this study is to evaluate the safety and efficacy of SAL-0951 in the treatment of chemotherapy-induced anemia (CIA) in patients with non-myeloid malignancies

Start Date14 Sep 2024

Sponsor / Collaborator

Shenzhen Salubris Pharmaceuticals Co., Ltd.

CTR20243024

/ RecruitingPhase 2

恩那度司他（SAL-0951）片在非髓系恶性肿瘤患者中治疗化疗引起贫血的平行、开放Ⅱ期临床研究

[Translation] A parallel, open-label phase II clinical study of Enadostat (SAL-0951) tablets in the treatment of chemotherapy-induced anemia in patients with non-myeloid malignancies

主要目的：评估恩那度司他（SAL-0951）片在非髓系恶性肿瘤患者中治疗化疗引起贫血的安全性。次要目的：评估恩那度司他（SAL-0951）片在非髓系恶性肿瘤患者中治疗化疗引起贫血的疗效。探索性目的：探索恩那度司他（SAL-0951）片在非髓系恶性肿瘤患者中治疗化疗引起贫血的红细胞相关检查值、铁代谢相关检查值的影响、药代动力学特征

[Translation]

Primary objective: To evaluate the safety of Enadostat (SAL-0951) tablets in the treatment of chemotherapy-induced anemia in patients with non-myeloid malignancies. Secondary objective: To evaluate the efficacy of Enadostat (SAL-0951) tablets in the treatment of chemotherapy-induced anemia in patients with non-myeloid malignancies. Exploratory objective: To explore the effects of Enadostat (SAL-0951) tablets on red blood cell-related examination values, iron metabolism-related examination values, and pharmacokinetic characteristics in the treatment of chemotherapy-induced anemia in patients with non-myeloid malignancies.

Start Date08 Sep 2024

Sponsor / Collaborator

Shenzhen Salubris Pharmaceuticals Co., Ltd.

100 Clinical Results associated with Enarodustat

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100 Translational Medicine associated with Enarodustat

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100 Patents (Medical) associated with Enarodustat

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Literatures (Medical) associated with Enarodustat

08 Jan 2025·Current Topics in Medicinal Chemistry

Bioanalysis, Analysis, Chemistry, and Pharmacological Aspects of Hypoxia-Inducible Factor Prolyl Hydroxylase Inhibitors

Article

Author: Sharma, Sanjay ; Patil, Roshani ; Jain, Sunidhi

Abstract:The development of Hypoxia-Inducible Factor Prolyl Hydroxylase Inhibitors (HIFPHIs), such as Roxadustat (ROX), Enarodustat (ENA), Desidustat (DES), Vadadustat (VAD), Molidustat (MOL), and Daprodustat (DAP), has significant effects on anemia in chronic kidney disease. This review presents comprehensive information about the synthesis, pharmacology, and analysis of HIF-PHIs across several matrices. The literature has presented several approaches for quantifying HIF-PHIs in diverse sample matrices. Furthermore, HIF-PHIs exhibit similar modes of action, demonstrating distinct pharmacokinetic parameters. The pharmacological insights encompass their half-life, mechanism of action, absorption, distribution, metabolism, excretion, and therapeutic uses. Research indicates that most studies concentrate on hyphenated methodologies for drug estimation in various biological fluids. Consequently, this study assesses the biological efficacy of HIF-PHIs and elucidates the analytical methodologies currently employed for measurement across various matrices.

16 Dec 2024·ChemMedChem

Crystallographic and Selectivity Studies on the Approved HIF Prolyl Hydroxylase Inhibitors Desidustat and Enarodustat

Article

Author: Kaur, Samanpreet ; Tumber, Anthony ; Corner, Thomas P. ; Nakashima, Yu ; Allen, Mark D. ; Schnaubelt, Lara I. ; Fiorini, Giorgia ; Schofield, Christopher J. ; Salah, Eidarus ; Brewitz, Lennart

AbstractProlyl hydroxylase domain‐containing proteins 1–3 (PHD1–3) are 2‐oxoglutarate (2OG)‐dependent oxygenases catalysing C‐4 hydroxylation of prolyl residues in α‐subunits of the heterodimeric transcription factor hypoxia‐inducible factor (HIF), modifications that promote HIF‐α degradation via the ubiquitin‐proteasome pathway. Pharmacological inhibition of the PHDs induces HIF‐α stabilisation, so promoting HIF target gene transcription. PHD inhibitors are used to treat anaemia caused by chronic kidney disease (CKD) due to their ability to stimulate erythropoietin (EPO) production. We report studies on the effects of the approved PHD inhibitors Desidustat and Enarodustat, and the clinical candidate TP0463518, on activities of a representative set of isolated recombinant human 2OG oxygenases. The three molecules manifest selectivity for PHD inhibition over that of the other 2OG oxygenases evaluated. We obtained crystal structures of Desidustat and Enarodustat in complex with the human 2OG oxygenase factor inhibiting hypoxia‐inducible factor‐α (FIH), which, together with modelling studies, inform on the binding modes of Desidustat and Enarodustat to active site Fe(II) in 2OG oxygenases, including PHD1–3. The results will help in the design of selective inhibitors of both the PHDs and other 2OG oxygenases, which are of medicinal interest due to their involvement inter alia in metabolic regulation, epigenetic signalling, DNA‐damage repair, and agrochemical resistance.

01 Nov 2024·Clinical and Experimental Nephrology

The comparison of four hypoxia-inducible factor prolyl hydroxylase inhibitors on drug potency and cost for treatment in patients with renal anemia

Article

Author: Imai, Atsuhiro ; Imai, Enyu

BACKGROUNDFive hypoxia-inducible factor prolyl hydroxylase inhibitors (HIF-PHIs) have been approved for marketing in Japan. However, marked differences exist in terms of drug potency, dose requirement, and pharmacokinetics.METHODSThe primary evaluation in this study was the changes in hemoglobin levels, dose escalation, drug potency, and cost among HIF-PHIs, 3 months after the initiation of treatment.RESULTSAll patients treated with HIF-PHI between August 2020 and December 2023 were enrolled in this study. In total, 124 patients were administered daprodustat (N = 37), enarodustat (N = 44), molidustat (N = 13), or vadadustat (N = 30). The mean hemoglobin levels of daprodustat, enarodustat, molidustat, and vadadustat at 3 months were 11.7 g/dL, 11.8 g/dL, 12.2 g/dL, and 11.3 g/dL, respectively. At 3 months, the mean doses of daprodustat, enarodustat, molidustat, and vadadustat increased by 110%, 177%, 125%, and 152%, respectively, from the initial dose. The HIF-PHI potency indices (HPI) of daprodustat, enarodustat, molidustat, and vadadustat at 3 months were 0.168, 0.307, 0.184, and 0.254, respectively. At 3 months, the mean daily costs of daprodustat, enarodustat, molidustat, and vadadustat were JPY 345, JPY 434, JPY 206, and JPY 565, respectively.CONCLUSIONThe difference in dose escalation for anemia treatment among HIF-PHIs is due to differences in drug potency, where the HPI significantly differs among HIF-PHIs. The disparity between the HPI and the cost of the initial dose accounts for the variance in the daily costs of renal anemia treatment among HIF-PHIs.

100 Deals associated with Enarodustat

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External Link

KEGG	Wiki	ATC	Drug Bank
D11523	Enarodustat	B03A	DB14985

R&D Status

Approved

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Indication	Country/Location	Organization	Date
chronic renal failure anemia	KR	JW PHARMACEUTICAL Corp.	17 Nov 2022
Anemia of renal disease	JP	Japan Tobacco, Inc.	25 Sep 2020

Developing

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
chronic renal failure anemia	Phase 3	CN	Shenzhen Salubris Pharmaceuticals Co., Ltd.	09 Dec 2020
Anemia in chronic kidney disease	Discovery	CN	Shenzhen Salubris Pharmaceuticals Co., Ltd.	08 Dec 2020
Kidney Failure, Chronic	Discovery	US	Akros Pharma, Inc.	01 May 2013

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Clinical Result

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


ASN2018	Phase 3	Anemia \| Chronic Kidney Diseases Maintenance	-	Enarodustat 2 mg	ddtahqtvce(ytqpbyazxl) = vjzzvmglcs vhkysfsqzq (tijbzhsqop )	Positive	23 Oct 2018
				Enarodustat 4 mg	ddtahqtvce(ytqpbyazxl) = oakeczoscc vhkysfsqzq (tijbzhsqop )
FP380 (ERA2015)	Not Applicable	Anemia in chronic kidney disease hemoglobin \| erythropoietin	22	JTZ-951 1 mg	(zcaqxzpoqf) = The results of reticulocyte count, hematocrit level and red blood cells in terms of changes from baseline at Week 6 were similar to that in hemoglobin znfeidnxxb (sdwnfqmkzn ) View more	Positive	21 May 2015
FO019 (ERA2015)	Not Applicable	Anemia \| Chronic Kidney Diseases Maintenance hemoglobin \| Erythropoiesis Stimulating Agents (ESAs) \| iv iron ... View more	40	JTZ-951 1 mg	(tixtadxuis) = The results of reticulocyte count, hematocrit level and red blood cells in terms of changes from baseline at week 8 were similar to that in hemoglobin lktndqrhia (waryvijjyg ) View more	Positive	21 May 2015
				JTZ-951 3 mg