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Surface here is educational only; do not use without medical supervision. Our editorial verdict is SKIP-FOR-NOW — current cost / risk / redundancy puts it below the line.
Roxadustat
FG-4592 / ASP1517 / Evrenzo / Aerlanil — first-in-class oral HIF-PHI that mimics altitude adaptation by stabilizing HIF-α
Aliases (6)
Overview
What is Roxadustat?
Roxadustat is the first-in-class oral hypoxia-inducible factor prolyl hydroxylase inhibitor (HIF-PHI), developed by FibroGen and partnered with Astellas (EU/Japan) and AstraZeneca (China; rights returned in US). It is approved for symptomatic anemia of chronic kidney disease in China (Dec 2018, brand 爱瑞卓 / Aerlanil), Japan (Sept 2019, Evrenzo), and the EU (Aug 2021, Evrenzo). The FDA REJECTED the NDA in August 2021 after the Cardiovascular and Renal Drugs Advisory Committee voted 13-1 against approval for non-dialysis CKD and 12-2 against approval for dialysis CKD, citing increased thrombosis, seizure, and mortality signals. WADA prohibits roxadustat under S2.1.2 (HIF activators/stabilizers); multiple high-profile athlete suspensions (Halep, cyclists) trace back to it.
Key Benefits
Oral, 3x-weekly dosing (vs 1-3x weekly EPO injections) for CKD anemia, simultaneously stimulates endogenous EPO and improves iron mobilization (suppresses hepcidin, raises TSAT), reduces IV-iron requirement compared to ESA therapy, and physiologically mimics altitude adaptation by stabilizing the same transcription factor (HIF-α) that hypoxia stabilizes naturally.
Mechanism of Action
Roxadustat reversibly inhibits HIF prolyl hydroxylase domain enzymes (PHD1/2/3) by competing with 2-oxoglutarate at their catalytic site. Under normoxia, PHDs hydroxylate proline residues on HIF-α, marking it for VHL-mediated proteasomal degradation. Inhibiting PHDs allows HIF-α to escape degradation, dimerize with HIF-β, translocate to the nucleus, and transactivate hypoxia-response genes — including erythropoietin (EPO), the EPO receptor, and iron-handling genes (DMT1, transferrin, transferrin receptor, ceruloplasmin) while suppressing hepcidin. Net effect: a controlled physiological mimic of high-altitude adaptation, raising RBC production while improving iron utilization.
Pharmacokinetics
Research Indications
The HIF system in 90 seconds
Hypoxia-Inducible Factor (HIF) is a heterodimeric transcription factor — HIF-α (one of three: HIF-1α, HIF-2α, HIF-3α) plus HIF-β (constit…
What roxadustat does
Roxadustat is a small-molecule competitive inhibitor of PHD1/2/3, sitting in the same active-site pocket as 2-oxoglutarate. It is reversi…
Why this looks like altitude adaptation
A climber spending three weeks at 4,000 m altitude experiences sustained tissue hypoxia, sustained HIF-α stabilization, and a measurable …
Research Protocols
Disclaimer: These are commonly discussed research protocols and not medical advice.
Quality Indicators
EU/Japan/China-pharmacy blister, intact
Evrenzo (EU/UK), Aerlanil (China FibroGen/AstraZeneca), Evrenzo (Japan Astellas) — pharmacy-dispensed blister with batch number is the gold standard. Imported tablets from a licensed pharmacy with intact packaging are pharma-grade.
Reddish-pink film-coated tablet, debossed strength
Evrenzo branded tablets are reddish-pink film-coated, debossed with strength (20/50/70/100/150). Reference label image vs. what arrives.
Generic Chinese roxadustat (post-2024)
Multiple Chinese generics launched after FibroGen patent expiry; legitimate but bioavailability and impurity profiles less well-characterized than originator.
Research-chemical powder / unbranded capsules
Gray-market 'FG-4592' raw powder or unmarked caps carry counterfeiting risk and unknown purity. WADA-detection sensitivity is high; positive doping tests have been linked to research-chem batches.
Vendor claims FDA approval
Roxadustat is NOT FDA approved (rejected Aug 2021). Any US vendor claiming FDA approval is fraudulent.
What to Expect
- Week 1Tolerability and dose-response.
- Week 2-4Early effect window.
- Week 4-8Peak benefit assessment.
- Week 8+Cycle decision point.
How was your experience with this compound?
Anonymous · one vote per session · results below at 5+ votes.
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