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Writer's pictureDženita Omerkić Dautović, MSc

💊 All You Need To Know About Jesduvroq

Updated: Jan 8


❓ What Is Jesduvroq?

  • ⚠️COMPLEX EXPLANATION: Jesduvroq is a commercial name for daprodustat. Daprodustat is an FDA-approved drug developed as an oral hypoxia-inducible factor prolyl hydroxylase (HIF-PH) inhibitor for treating anemia. HIF-PH inhibitors like daprodustat stimulate the production of red blood cells by increasing erythropoietin (EPO) levels [citation].

  • ⚠️SIMPLE EXPLANATION: Jesduvroq, also known as daprodustat, is a drug approved by the FDA for treating anemia. It works by blocking an enzyme called hypoxia-inducible factor prolyl hydroxylase (HIF-PH), which leads to an increase in red blood cell production by raising levels of a substance called erythropoietin (EPO).



Figure 1: Chemical Structure Depiction of Daprodustat, Source: https://pubchem.ncbi.nlm.nih.gov/
Figure 1: Chemical Structure Depiction of Daprodustat, Source: https://pubchem.ncbi.nlm.nih.gov/



🧪 What Is Hypoxia-Inducible Factor Prolyl Hydroxylase (HIF-PH)?

  • Complex explanation (Check below for simple explanation):

    • Hypoxia-inducible factor prolyl hydroxylase (HIF-PH) is an enzyme that regulates the hypoxia-inducible factor (HIF) pathway.

    • The hypoxia-inducible factor (HIF) is a transcription factor that regulates gene expression in various cellular processes, including metabolism, angiogenesis, and erythropoiesis (red blood cell production).

    • HIF-PH regulates HIF by hydroxylating it in the presence of oxygen, marking it for degradation by the proteasome. Under low oxygen (hypoxia), HIF-PH is inhibited, leading to the stabilization and activation of HIF, which then induces the expression of target genes involved in adapting to low-oxygen environments.

    • This is why HIF-PH inhibitors are being developed to treat conditions where HIF activation could be beneficial, such as anemia and ischemic diseases [citation; citation].

  • Simple explanation:

    • Hypoxia-inducible factor prolyl hydroxylase (HIF-PH) is an enzyme that controls the hypoxia-inducible factor (HIF) pathway, important for regulating genes related to metabolism, blood vessel formation, and red blood cell production.

    • HIF-PH works by adding oxygen to HIF, which leads to its breakdown, but when oxygen levels are low, HIF-PH activity decreases, allowing HIF to become stable and active.

    • This triggers the activation of genes that help the body adapt to low oxygen.

    • Therefore, drugs that inhibit HIF-PH are being researched to treat conditions like anemia and ischemic diseases, where activating HIF could be helpful.


🩸 What Is Erythropoietin (EPO)?

  • Erythropoietin (EPO) is a hormone produced primarily by the kidneys in response to low oxygen levels, known as hypoxia.

  • 90% of the overall EPO in human adults is produced by renal interstitial fibroblasts [citation]. EPO stimulates the bone marrow to produce more red blood cells, which carry oxygen to tissues.

  • EPO is commonly used to treat anemia, characterized by a low red blood cell count, in people with chronic kidney disease, cancer, and other conditions [citation].

  • EPO is also banned in sports, as its ability to increase red blood cell production can enhance athletic performance [citation; citation].


💉 For What Is Used Jesduvroq (Daprodustat)?

  • ⚠️ Jesduvroq (Daprodustat) or GSK1278863, is approved to treat anemia associated with chronic kidney disease (CKD) and myelodysplastic syndromes (MDS) who may have difficulty tolerating traditional erythropoietin-stimulating agents (ESAs) or who may have a suboptimal response to ESAs.

  • Jesduvroq is a small-molecule drug [citation], and it belongs to the group of oral hypoxia-inducible factor prolyl hydroxylase (HIF-PH) inhibitors, which means it works by stimulating the production of red blood cells [citation; citation].

  • Jesduvroq has shown promising results in clinical trials and has been submitted for regulatory approval in several countries [citation]. The US Food and Drug Administration (FDA) has approved Jesduvroq at the beginning of 2023, in February [citation].

🧑🏽‍🔬 Who Developed Jesduvroq?

  • 🏭 Daprodustat is manufactured by GlaxoSmithKline (GSK). GSK is a multinational pharmaceutical company specializing in researching, developing, and producing pharmaceuticals, vaccines, and consumer health products [citation].

  • GlaxoSmithKline (GSK) was formed in 2000 through the merger of Glaxo Wellcome and SmithKline Beecham.

  • GSK has operations in more than 150 countries and is one of the largest pharmaceutical companies in the world.

  • The company's product portfolio includes treatments for various of conditions, including respiratory, autoimmune, infectious diseases, oncology, diabetes, and mental health. In addition to its pharmaceutical products, GSK produces consumer health products, such as oral care products, vitamins, and pain relievers [citation].


⚗️ What Is the Mechanism of Action of Jesduvroq?

  • ⚗️Daprodustat is a reversible inhibitor of HIF-PH1, PH2, and PH3. It works by inhibiting HIF-PH and increasing the level of HIF in the body. This leads to the stimulation of processes such as:

    • Angiogenesis (the formation of new blood vessels)

    • Production of erythropoietin (a hormone that stimulates the production of red blood cells), and

    • Stimulation of glycolysis (the breakdown of glucose for energy production) [citation].

  • Therefore, inhibitors of HIF-PH, such as daprodustat, can increase the level of HIF in the body and stimulate these processes, making them a promising target for treating anemia and other conditions associated with hypoxia [citation].


🙂What Are the Key Advantages of Jesduvroq (Daprodustat)?

  • Daprodustat offers a new treatment option for patients with anemia, particularly those with chronic kidney disease (CKD) or myelodysplastic syndromes (MDS) who may have difficulty tolerating traditional erythropoietin-stimulating agents (ESAs) or may have suboptimal responses to ESAs.

  • Several key advantages have been proposed for daprodustat:

    • Oral administration: Unlike current treatments for anemia, such as erythropoietin-stimulating agents (ESAs) and intravenous iron, daprodustat is taken orally, making it more convenient for patients.

    • Improved patient experience: By avoiding the need for intravenous administration, daprodustat may improve the patient experience and increase treatment adherence.

    • Potential for improved safety profile: Daprodustat is designed to maintain stable HIF levels and avoid the surges associated with ESAs. This may result in a lower risk of cardiovascular events and other adverse effects.

    • Efficacy: In early clinical trials, daprodustat has shown promising efficacy in treating anemia associated with CKD and MDS.

    • Mechanism of action: By inhibiting HIF-PH and increasing HIF levels, daprodustat addresses the root cause of anemia rather than simply treating its symptoms.

⚠️What Are the Key Warnings and Precautions of Jesduvroq?

  • ⚠️The most crucial information about Jesduvroq is that it may cause serious side effects. The main ones are:

    • Increased risk of death, myocardial infarction, stroke, venous thromboembolism, and thrombosis of vascular access,

    • Risk of hospitalization for heart failure,

    • Hypertension,

    • Gastrointestinal erosion,

    • Serious adverse events in patients with anemia due to chronic kidney disease and not on dialysis and,

    • Malignancy.

  • For more information, please read the official documentation [citation].


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