Enarodustat (JTZ-951): FAQs for Researchers

Enarodustat (JTZ-951) is a selective, orally active inhibitor of hypoxia-inducible factor prolyl hydroxylase domain (HIF-PHD) enzymes, investigated for its ability to stabilize HIF-α subunits and stimulate endogenous erythropoietin production in anemia research models.

Chemical Name / Synonyms

Enarodustat; JTZ-951

Aladdin SKU

E421099

Primary Target

HIF Prolyl Hydroxylase Domain enzymes (PHD1, PHD2, PHD3)

Mechanism of Action

Competitive inhibition of 2-oxoglutarate-dependent PHD enzymes, stabilizing HIF-α and upregulating EPO transcription

Primary Research Application

Anemia of chronic kidney disease (CKD) models; erythropoiesis studies

Administration Route (research use)

Oral (in vivo studies); dissolved in suitable vehicle for in vitro use

What Is Enarodustat (JTZ-951) and How Does It Work?

Enarodustat, also designated JTZ-951, is a small-molecule inhibitor of the hypoxia-inducible factor prolyl hydroxylase domain (HIF-PHD) enzyme family, comprising PHD1, PHD2, and PHD3. Under normoxic conditions, PHD enzymes hydroxylate the HIF-α subunit, targeting it for proteasomal degradation via the von Hippel-Lindau (VHL) E3 ubiquitin ligase complex. By competitively inhibiting these 2-oxoglutarate-dependent dioxygenases, Enarodustat prevents HIF-α hydroxylation and degradation, allowing HIF-α to accumulate and translocate to the nucleus.

Once stabilized, HIF-α dimerizes with HIF-1β and drives transcription of hypoxia-response genes, most notably EPO (erythropoietin) in the kidney and liver. The resulting increase in endogenous EPO stimulates red blood cell production, making Enarodustat a valuable pharmacological tool for studying erythropoiesis and the hypoxia-signaling axis in research settings.

What Are the Key Research Applications of Enarodustat?

Enarodustat is primarily used as a research tool compound in the following contexts:

• Anemia of chronic kidney disease (CKD) models: Researchers use Enarodustat to mimic therapeutic HIF-PHD inhibition in rodent CKD models to study EPO induction and erythrocyte dynamics.
• Hypoxia pathway studies: As a PHD inhibitor, it enables controlled activation of the HIF transcriptional program without subjecting cells or animals to true hypoxic conditions.
• Iron metabolism research: HIF stabilization by PHD inhibitors modulates hepcidin expression and iron absorption pathways, providing a tool to study iron homeostasis.
• Comparative PHD inhibitor studies: Enarodustat can be compared with other PHD inhibitors (e.g., Roxadustat, Daprodustat, Vadadustat) to dissect selectivity profiles and downstream biology.

All uses described are strictly for in vitro and in vivo preclinical research purposes only. This product is not intended for human therapeutic use.

Storage, Handling, and Solubility Guidance

Proper storage and handling are essential to maintain the integrity of Enarodustat (JTZ-951). The following general guidelines apply; always refer to the Certificate of Analysis (CoA) supplied with your specific lot for definitive specifications:

• Storage temperature: Store at −20 °C, protected from light and moisture, in a tightly sealed container.
• Solubility: Enarodustat is reported to be soluble in DMSO. Prepare concentrated stock solutions in DMSO and dilute into aqueous buffers or cell culture media immediately before use, keeping the final DMSO concentration ≤0.1% to avoid cytotoxic effects.
• Stability: Avoid repeated freeze-thaw cycles; aliquot stock solutions upon first reconstitution.
• Handling precautions: Handle as a research chemical with standard laboratory precautions. Consult the Safety Data Sheet (SDS) before use. Wear appropriate PPE including gloves and eye protection.

Note: Specific solubility values and storage conditions should be confirmed from the product CoA and SDS available on the Aladdin Scientific product page for SKU E421099.

Ordering, Purity, and Quality Information

Enarodustat (JTZ-951) is available from Aladdin Scientific under SKU E421099. The following quality and ordering points are relevant for procurement:

• Purity: Aladdin Scientific research-grade compounds are typically characterized by HPLC and confirmed by NMR or MS. Refer to the CoA for the confirmed purity of your specific lot.
• Available formats: Contact Aladdin Scientific sales or check the product page for available pack sizes and bulk inquiry options.
• Documentation: CoA, SDS, and structural confirmation data are available upon request or via the product listing.
• Reference product: Per the product description, please also refer to related SKU E414445 for cross-reference purposes.

For ordering inquiries, volume pricing, or custom synthesis questions, contact Aladdin Scientific customer service directly.

Frequently asked questions

What is the mechanism of action of Enarodustat (JTZ-951)?

Enarodustat competitively inhibits HIF prolyl hydroxylase domain (PHD) enzymes, which are 2-oxoglutarate-dependent dioxygenases responsible for hydroxylating and targeting HIF-α for proteasomal degradation. By blocking PHD activity, Enarodustat stabilizes HIF-α, promotes its nuclear translocation, and drives transcription of downstream hypoxia-response genes including EPO, thereby stimulating erythropoiesis.

What solvents can be used to dissolve Enarodustat (JTZ-951) for in vitro experiments?

Enarodustat is generally reported to be soluble in DMSO, which is the recommended solvent for preparing stock solutions. Working solutions should be prepared by diluting the DMSO stock into the appropriate aqueous medium immediately before use, maintaining a final DMSO concentration of ≤0.1% to minimize solvent-related cytotoxicity. Always confirm solubility data with the lot-specific CoA provided by Aladdin Scientific.

How should Enarodustat (JTZ-951) be stored to ensure long-term stability?

Enarodustat should be stored at −20 °C in a tightly sealed container, protected from light and moisture. To preserve compound integrity, avoid repeated freeze-thaw cycles by preparing single-use aliquots from the stock solution upon first reconstitution. Refer to the product CoA and SDS for lot-specific stability data.

Is Enarodustat (JTZ-951) suitable for in vivo animal studies?

Yes, Enarodustat has been investigated in preclinical in vivo studies, including rodent models of anemia of chronic kidney disease, and is reported to be orally active. Researchers should optimize dosing, vehicle formulation, and administration schedule based on their specific experimental model. This compound is supplied for research use only and is not approved for clinical or veterinary therapeutic use.

What is the difference between Enarodustat (JTZ-951) and other PHD inhibitors like Roxadustat?

Enarodustat (JTZ-951) and Roxadustat (FG-4592) both inhibit HIF-PHD enzymes to stabilize HIF-α and induce EPO production, but they differ in their chemical scaffolds, reported selectivity profiles among PHD isoforms, pharmacokinetic properties, and the specific clinical or research contexts in which they have been studied. Researchers should select the compound best suited to their experimental question and consult the primary literature for comparative data.

References

1. Tanaka T, et al. Enarodustat (JTZ-951): Research publications describing PHD inhibition and EPO induction. [Specific citation details not available in source material; requires literature search.]
2. Aladdin Scientific Product Page: Enarodustat (JTZ-951), SKU E421099. Aladdin Scientific, Shanghai. [URL to be confirmed from live site.]
3. Semenza GL. Hypoxia-inducible factors in physiology and medicine. Cell. 2012;148(3):399-408. [General HIF pathway reference; confirm relevance and accuracy.] doi:10.1016/j.cell.2012.01.021

Products are supplied for research and development use only. Not for use in humans, animals, diagnosis, or therapy.