Jesduvroq (daprodustat)
Research Synopsis
- - Jesduvroq (daprodustat) is a hypoxia-inducible factor prolyl hydroxylase inhibitor being explored as a treatment for anemia related to chronic kidney disease (CKD) and represents a novel approach to enhancing erythropoiesis.
- - Clinical trials have indicated that daprodustat can effectively increase hemoglobin levels in patients with anemia, both in those undergoing dialysis and those not on dialysis.
- - Phase 3 trials have shown that daprodustat is generally well tolerated, although some mild to moderate adverse effects have been reported, mainly gastrointestinal in nature.
- - Daprodustat works by mimicking mild hypoxia in the body, promoting the natural production of erythropoietin (EPO) which can enhance red blood cell production without some complications associated with traditional erythropoiesis-stimulating agents (ESAs).
- - Research has raised potential safety concerns regarding the long-term effects of HIF inhibitors, including risks associated with cardiovascular health and tumor growth.
- - Drug interaction studies show that daprodustat does not significantly affect the plasma levels of certain medications, suggesting a low potential for drug-drug interactions, though certain combinations do increase its plasma concentration.
- - Daprodustat is also studied for its role in potential muscle injury recovery, demonstrating benefits in reducing muscle damage markers after exercise, indicative of broader therapeutic applications beyond just treating anemia.
- - Further longitudinal studies are necessary to fully understand the safety profile and long-term benefits of daprodustat in various patient populations, particularly those with CKD and anemia.
- - The potential misuse of HIF stabilizers, including daprodustat, in sports and by athletes remains a concern, as these agents may enhance performance by increasing oxygen transport capacity.
- - Overall, daprodustat represents a significant advancement in the treatment landscape for anemia in CKD, positioning it as a promising alternative to existing therapies, albeit with ongoing research required to address safety and efficacy concerns.
Jesduvroq (daprodustat)
Hypoxia-inducible factor stabilizers and other small-molecule erythropoiesis-stimulating agents in current and preventive doping analysis.
London, UK
2 hours ago
1 Received
- The use of erythropoiesis-stimulating agents (ESAs) to boost oxygen transport in the blood is considered a prohibited method of performance enhancement by the World Anti-Doping Agency (WADA).
- New orally available small-molecule ESAs, like hypoxia-inducible factor (HIF) stabilizers, are being developed as potential therapies for anemia, raising concerns about their potential misuse in sports.
- The text reviews various experimental HIF stabilizers and ongoing clinical trials for anti-anemia drugs, as well as the analytical methods used for detecting these substances in sports drug testing.
$100 - $150
Hourly Rate
Effect of food and gemfibrozil on the pharmacokinetics of the novel prolyl hydroxylase inhibitor GSK1278863.
London, UK
2 hours ago
1 Received
- - Anemia, often seen in chronic kidney disease, is typically treated with erythropoiesis-stimulating agents, but a new drug, GSK1278863, shows promise as it promotes red blood cell production through a different mechanism by increasing hypoxia-inducible factor 1α levels.
- - A study tested the effects of taking GSK1278863 alone, with a high-fat meal, and with gemfibrozil, a strong inhibitor of the enzyme that metabolizes the drug, CYP2C8.
- - Results showed that food doesn't significantly impact GSK1278863's effectiveness, but if taken with gemfibrozil, the drug's concentration in the body can dramatically increase, which
$100 - $150
Hourly Rate
Short-term treatment with a novel HIF-prolyl hydroxylase inhibitor (GSK1278863) failed to improve measures of performance in subjects with claudication-limited peripheral artery disease.
London, UK
2 hours ago
1 Received
- The study investigated the safety and effectiveness of GSK1278863, an oral PHD inhibitor, in improving conditions related to peripheral artery disease (PAD) compared to a placebo.
- Two treatment approaches were tested: a single dose of 300 mg and a daily dose of 15 mg for 14 days, but neither showed any advantages in exercise performance.
- More adverse events were reported in those taking GSK1278863 versus placebo, indicating the need for further research with larger samples before concluding its safety and utility for PAD treatment.
$100 - $150
Hourly Rate
Role of hypoxia-inducible factors in acute kidney injury.
London, UK
2 hours ago
1 Received
- Oxygen is essential for mammals, and when it's lacking (hypoxia), cells activate proteins called hypoxia-inducible factors (HIF) to help adapt.
- Research in animals shows that the HIF pathway plays a significant role in acute kidney injury (AKI), leading to early clinical trials in humans that focus on this pathway.
- The review will highlight recent important findings from both preclinical and clinical studies about how the HIF pathway relates to the development of AKI.
$100 - $150
Hourly Rate
Pharmacokinetics, pharmacodynamics and safety of single, oral doses of GSK1278863, a novel HIF-prolyl hydroxylase inhibitor, in healthy Japanese and Caucasian subjects.
London, UK
2 hours ago
1 Received
- The study assessed the pharmacokinetics, pharmacodynamics, and safety of GSK1278863, a new prolyl hydroxylase inhibitor, through a single oral dose administration in Japanese (19 participants) and Caucasian (14 participants) subjects.
- Increased exposure (measured by AUCinf) to the drug was found in Japanese subjects, likely related to differences in body weight, though both groups showed dose-proportional increases.
- Significant increases in erythropoietin and vascular endothelial growth factor were noted in the Japanese group with higher doses, and while some adverse effects occurred, GSK1278863 was generally well tolerated with no notable ethnic differences in pharmacokinetic or pharmacodynamic responses.
$100 - $150
Hourly Rate
Overcoming bioanalytical challenges associated with the separation and quantitation of GSK1278863, a HIF-prolyl hydroxylase inhibitor, and its 14 stereoisomeric metabolites.
London, UK
2 hours ago
1 Received
- GSK1278863 is an experimental drug being studied to treat anemia related to chronic kidney disease and is mainly processed by P450 enzymes, producing 19 different metabolic forms.
- Two complex ultra high performance liquid chromatography (UHPLC) methods were created to analyze both the drug and its metabolites, but five of the six oxidative metabolites exist as different stereoisomers, leading to a total of 14 variations.
- Ultimately, a supercritical fluid chromatography (SFC) technique was developed to effectively separate these stereoisomeric metabolites, providing crucial insight into the specific forms present in humans.
$100 - $150
Hourly Rate
Four-Week Studies of Oral Hypoxia-Inducible Factor-Prolyl Hydroxylase Inhibitor GSK1278863 for Treatment of Anemia.
London, UK
2 hours ago
1 Received
- Hypoxia-inducible factor prolyl hydroxylase inhibitors, like GSK1278863, help stabilize hypoxia-inducible factor levels which boost the production of erythropoietin and other genes related to low oxygen levels.
- Two phase 2a studies were conducted to assess how different dosages of GSK1278863 affected hemoglobin levels in patients with anemia of chronic kidney disease (CKD), both those not on dialysis and those undergoing hemodialysis.
- Results showed that higher doses of GSK1278863 increased hemoglobin in nondialysis patients and maintained levels in hemodialysis patients switching from erythropoietin, with the treatment being generally safe and well
$100 - $150
Hourly Rate
A Novel Hypoxia-Inducible Factor-Prolyl Hydroxylase Inhibitor (GSK1278863) for Anemia in CKD: A 28-Day, Phase 2A Randomized Trial.
London, UK
2 hours ago
1 Received
- Anemia related to chronic kidney disease (CKD) often needs treatment with erythropoietin (EPO), and GSK1278863 is a new oral drug designed to boost the body's own EPO production while also enhancing red blood cell production through alternative mechanisms.
- The study was a multicenter, single-blind, randomized trial involving anemic patients with different stages of CKD, where participants received either GSK1278863 or a placebo for 28 days to evaluate its effects.
- The results showed that GSK1278863 led to significant increases in EPO levels and hemoglobin in participants, with many experiencing notable improvements, but some withdrew from the study due to high hemoglobin levels; limitations included
$100 - $150
Hourly Rate
Mass spectrometric characterization of a prolyl hydroxylase inhibitor GSK1278863, its bishydroxylated metabolite, and its implementation into routine doping controls.
London, UK
2 hours ago
1 Received
- Elite sports face risks of drug misuse, prompting anti-doping authorities to consider and integrate potential performance-enhancing drugs like GSK1278863 into testing programs.
- GSK1278863, a hypoxia-inducible factor (HIF) inhibitor, can significantly improve oxygen transport by increasing red blood cell production, raising concerns about its abuse in sports.
- The study focuses on the mass spectrometric behavior of GSK1278863 and its metabolite for developing efficient urine testing methods to detect these substances in athlete samples.
$100 - $150
Hourly Rate
Investigational therapies for renal disease-induced anemia.
London, UK
2 hours ago
1 Received
- The treatment of chronic kidney disease (CKD) related anemia primarily relies on peptidic erythropoiesis stimulating agents (ESAs) and iron supplements, both backed by long-term safety and effectiveness data but facing clinical and economic challenges.
- Recent advancements include next-generation ESAs, new iron formulations, and innovative therapies targeting erythropoietin synthesis and hematopoiesis, but these also come with their own set of challenges.
- Alternative treatments such as oral hypoxia-inducible factor (HIF) stabilizers (like molidustat, daprodustat, and roxadustat) show promise due to their benefits on iron balance and potential for convenience, though they raise safety concerns that
$100 - $150
Hourly Rate
Hypoxia-Inducible Factor Prolyl Hydroxylase Inhibitors: A Potential New Treatment for Anemia in Patients With CKD.
London, UK
2 hours ago
1 Received
- Erythropoiesis-stimulating agents (ESAs) have been used since 1989 to treat anemia in chronic kidney disease (CKD) by increasing hemoglobin and reducing transfusions; however, they carry risks of cardiovascular issues and other complications.
- New HIF prolyl hydroxylase (PH) enzyme inhibitors are emerging as an alternative, working by enhancing natural erythropoietin production and improving iron availability, with the added benefit of being taken orally, which could be more convenient for patients.
- Although HIF-PH inhibitors show promise for safer blood management with fewer side effects compared to ESAs, long-term studies are needed to confirm their effects, especially concerning potential risks like tumor growth
$100 - $150
Hourly Rate
HIF-prolyl hydroxylases as therapeutic targets in erythropoiesis and iron metabolism.
London, UK
2 hours ago
1 Received
- A primary response to low oxygen levels (systemic hypoxia) is the body’s increase in red blood cell production, managed by the HIF pathway.
- The HIF pathway plays a significant role in various cellular functions, and its discovery has spurred the creation of small molecules that boost the natural production of erythropoietin and improve iron metabolism.
- This review highlights the cellular and molecular processes involved in HIF-induced production of red blood cells and discusses recent clinical findings on treatments targeting HIF-prolyl hydroxylases for treating anemia.
$100 - $150
Hourly Rate
A Randomized, Placebo- and Positive-Controlled, Single-Dose, Crossover Thorough QT/QTc Study Assessing the Effect of Daprodustat on Cardiac Repolarization in Healthy Subjects.
London, UK
2 hours ago
1 Received
- - Daprodustat, in phase 3 trials for treating anemia linked to chronic kidney disease, was tested for effects on heart function with 55 healthy volunteers receiving varying doses (75 and 500 mg) alongside moxifloxacin and placebo.
- - The study found no significant increase in heart repolarization (QT interval) for daprodustat, with small decreases recorded that are not clinically important; however, moxifloxacin showed a notable increase.
- - Adverse events were reported by 73% of participants, mostly from the 500 mg daprodustat group, which had more gastrointestinal issues, though the 75 mg dose was generally well tolerated with no new safety concerns.
$100 - $150
Hourly Rate
Discovery and Preclinical Characterization of GSK1278863 (Daprodustat), a Small Molecule Hypoxia Inducible Factor-Prolyl Hydroxylase Inhibitor for Anemia.
London, UK
2 hours ago
1 Received
- * Hypoxia-inducible factors (HIF) help the body respond to low oxygen levels and stimulate red blood cell production, but are regulated by prolyl hydroxylases (PHDs) that degrade them; inhibiting PHDs might mimic mild hypoxia and promote healthier erythropoiesis.
- * GSK1278863 is a new drug that inhibits PHDs, increasing EPO production effectively
$100 - $150
Hourly Rate
Targeting Hypoxia-Inducible Factors for the Treatment of Anemia in Chronic Kidney Disease Patients.
London, UK
2 hours ago
1 Received
- Anemia is a common issue in chronic kidney disease (CKD), traditionally linked to low erythropoietin production, but now also associated with problems in iron metabolism and increased hepcidin activity.
- Current treatments include erythropoiesis-stimulating agents, iron supplements, and blood transfusions, but there are safety concerns, prompting the exploration of new options like targeting hypoxia-inducible factors (HIFs).
- The review highlights the HIF pathway's role in regulating erythropoiesis and iron metabolism, discussing the development and clinical trials of HIF prolyl hydroxylase inhibitors as a promising alternative for managing anemia in CKD patients.
$100 - $150
Hourly Rate
An Emerging Treatment Alternative for Anemia in Chronic Kidney Disease Patients: A Review of Daprodustat.
London, UK
2 hours ago
1 Received
- - The article discusses a new treatment for anemia related to chronic kidney disease that is in phase III development.
- - It highlights positive results from earlier phase II trials and details the drug's characteristics and mechanisms.
- - If the drug receives approval, it could greatly improve how anemia is managed in patients with chronic kidney disease.
$100 - $150
Hourly Rate
Effects of Daprodustat, a Novel Hypoxia-Inducible Factor Prolyl Hydroxylase Inhibitor on Anemia Management in Japanese Hemodialysis Subjects.
London, UK
2 hours ago
1 Received
- Daprodustat is an oral medication being tested for anemia treatment in Japanese patients with chronic kidney disease undergoing hemodialysis.
- In a 4-week study, patients were given either daprodustat or a placebo after pausing their usual anemia treatments, and the effects on hemoglobin levels were measured.
- Results indicated that higher doses of daprodustat (4-10 mg) led to significant increases in hemoglobin compared to placebo, with an increase in erythropoietin levels but no significant change in vascular endothelial growth factor levels.
$100 - $150
Hourly Rate
The drug interaction potential of daprodustat when coadministered with pioglitazone, rosuvastatin, or trimethoprim in healthy subjects.
London, UK
2 hours ago
1 Received
- The study aimed to evaluate daprodustat's ability to cause drug-drug interactions with the CYP2C8 enzyme and OATP1B1 transporter using pioglitazone and rosuvastatin as test drugs.
- Results showed that daprodustat did not significantly affect the plasma levels of pioglitazone and rosuvastatin, suggesting low interaction potential as a perpetrator.
- However, when daprodustat was taken with trimethoprim, a weak CYP2C8 inhibitor, its plasma concentration increased by 48%, indicating a moderate increase in absorption with the presence of weak inhibitors.
$100 - $150
Hourly Rate
An Exploratory Study of Daprodustat in Erythropoietin-Hyporesponsive Subjects.
London, UK
2 hours ago
1 Received
- Hyporesponsiveness to rhEPO in chronic kidney disease patients on hemodialysis is a significant concern, leading researchers to investigate daprodustat as a potential treatment to address this issue.
- A phase 2a study involved 15 participants with anemia on hemodialysis, taking daprodustat over 16 weeks, with the goal of maintaining hemoglobin levels between 10.0-11.5 g/dl.
- Results showed that 29% of subjects experienced meaningful increases in hemoglobin, and while many had adverse effects, most were mild to moderate with no new safety concerns raised.
$100 - $150
Hourly Rate
HIF prolyl hydroxylase inhibition protects skeletal muscle from eccentric contraction-induced injury.
London, UK
2 hours ago
1 Received
- The study investigates how prolyl hydroxylase inhibitors, which stabilize hypoxia-inducible factors (HIFs), can enhance skeletal muscle repair after injury in both mice and humans, potentially countering issues like fibrosis and fatty tissue buildup.* -
- In mouse experiments, the inhibitor GSK1120360A significantly improved muscle recovery post-injury, working through myeloid HIF1α and iNOS activity rather than EPO modulation.* -
- Tests in healthy human volunteers showed that the inhibitor daprodustat reduced muscle damage markers after exercise, but did not improve functional recovery, indicating some similarities and differences in response between species.*
$100 - $150
Hourly Rate