Nutrabiotech Vadadustat 98% 3G Powder, 98% high purity Vadadustat powder, selective HIF-PHI inhibitor, HIF-α stabilizer, endogenous erythropoietin regulator, renal anemia research raw material

Vadadustat CAS 1000025‑07‑9 (AKB‑6548) High‑Purity Powder HIF‑Prolyl Hydroxylase Inhibitor Biochemical Reagent

High‑purity Vadadustat powder CAS 1000025‑07‑9, also well‑known as AKB‑6548, PG‑1016548 and drug brand Vafseo, is a potent reversible hypoxia‑inducible factor prolyl‑hydroxylase (HIF‑PH) inhibitor. This off‑white crystalline small‑molecule compound stabilizes HIF‑1α and HIF‑2α transcription factor, boosts endogenous erythropoietin secretion, improves iron mobilization and accelerates red‑blood‑cell generation. It is widely used for laboratory research on chronic‑kidney‑disease‑caused anemia, erythropoiesis mechanism, iron‑metabolism and renal‑related pharmacology experiments. Every‑batch passes strict HPLC purity inspection, bulk‑order service and customizable‑packaging are available for global nephrology‑biochemistry researchers.

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Vadasustat (AKB-6548) CAS 1000025-07-9 | HIF-PH Inhibitor, HIF Stabilizer, Anemia of CKD Research

Vadasustat CAS 1000025-07-9
Oral HIF-PH Inhibitor for Anemia of CKD Research

Vadasustat (AKB-6548, PG-1016548) is a potent, titratable, orally active inhibitor of hypoxia-inducible factor prolyl-hydroxylases (HIF-PH; PHD / EGLN enzymes). It prevents HIF-α hydroxylation, stabilizing HIF-1α and HIF-2α to drive endogenous erythropoietin (EPO) production — a leading mechanism for treating anemia of chronic kidney disease (CKD).

HIF-PH Inhibitor HIF Stabilizer EPO Inducer Anemia of CKD Orally Active Hypoxia Pathway VHL Modulator
Request a Quote Get Technical Specs
306.70
MW (C14H11ClN2O4)
≥98%
Purity (HPLC)
0.19–0.56 nM
Ki HIF-PH1/2/3

Molecular Information

Name: Vadasustat (AKB-6548)
CAS: 1000025-07-9
Formula: C₁₄H₁₁ClN₂O₄
MW: 306.70 g/mol
Purity: ≥98% (HPLC)
Solubility: DMSO ≈2 mg/mL
MP: 172-174°C
Targets: HIF-PH1 / 2 / 3

Vadasustat at a Glance

Key pharmacological and physicochemical properties of research-grade Vadasustat (AKB-6548, CAS 1000025-07-9)

🎯
Target Class
HIF-PH / PHD Inhibitor
⚡
Potency
Ki 0.19–0.56 nM
🧬
Stabilizes
HIF-1α / HIF-2α
🩸
Primary Effect
EPO Induction
💊
Indication
Anemia of CKD
📦
Route
Oral / Titratable
⚗️
Molecular Wt
306.70 g/mol
✅
Purity
≥98% (HPLC)

Detailed Specifications & Quality Control

Full analytical characterization and QC release testing for every batch of Vadasustat (AKB-6548)

📋 Detailed Specifications

  • CAS Number1000025-07-9
  • SynonymsAKB-6548, PG-1016548, Vadadustat
  • Molecular FormulaC₁₄H₁₁ClN₂O₄
  • Molecular Weight306.70 g/mol
  • Purity≥98% (HPLC)
  • AppearanceWhite to off-white solid
  • Melting Point172-174°C
  • Storage-20°C, sealed, dry, dark
  • SolubilityDMSO ≈2 mg/mL; DMF; EtOH
  • SMILESO=C(O)CNC(=O)c1ncc(-c2cccc(Cl)c2)cc1O
  • InChIKeyJGRXMPYUTJLTKT-UHFFFAOYSA-N
  • PubChem CID23634441

🔬 Quality Control Release Tests

  • HPLC Purity≥98.0%
  • NMR (⁴H)Conforms to structure
  • LC-MS / MSM+1 confirmed
  • Melting Point172-174°C
  • Loss on Drying≤0.5%
  • Residue on Ignition≤0.10%
  • Heavy Metals≤10 ppm
  • Residual SolventsICH Q3C conformance
  • UV / λmax262, 317 nm
  • IdentityIR / NMR match
  • Endotoxin (optional)On request
  • COA / MSDSIncluded / on request

Key Molecular Targets

Vadasustat (AKB-6548) acts on the HIF prolyl-hydroxylase / oxygen-sensing axis

🧩 HIF-PH1 (PHD1 / EGLN2) 🧩 HIF-PH2 (PHD2 / EGLN1) 🧩 HIF-PH3 (PHD3 / EGLN3) 🧬 HIF-1α 🧬 HIF-2α 🩸 Erythropoietin (EPO) 🔗 ARNT (HIF-β) ⚙️ 2-Oxoglutarate Site 🏷️ VHL E3 Ligase Axis

Mechanism of Action — How Vadasustat Works

Inhibition of HIF prolyl-hydroxylases stabilizes HIF and restores endogenous erythropoietin production

1

Target Engagement

Vadasustat enters cells and binds the Fe²⁺-containing catalytic site of HIF prolyl-hydroxylases, competing with 2-oxoglutarate (2-OG).

2

Blocks Hydroxylation

It blocks prolyl hydroxylation of HIF-α subunits at Pro402 / Pro564, the modification that normally flags HIF-α for destruction.

3

Escapes VHL

Non-hydroxylated HIF-α is no longer recognized by the VHL E3 ubiquitin ligase complex, escaping ubiquitination and proteasomal degradation.

4

HIF-α Stabilization

HIF-α protein accumulates in the cytosol and translocates to the nucleus, where it can exert transcriptional activity.

5

Heterodimerization

HIF-α dimerizes with ARNT (HIF-β) and binds hypoxia response elements (HREs) in target gene promoters.

6

Erythropoiesis

Transcription of EPO, transferrin and erythroid genes is induced, stimulating red blood cell production — the basis of CKD anemia therapy.

Research Applications of Vadasustat (AKB-6548)

A versatile HIF-PH inhibitor probe across renal, hypoxia, erythropoiesis and oxygen-sensing research

🩸

Anemia of CKD

First-in-class HIF-stabilizing mechanism to model and study renal anemia without exogenous erythropoiesis-stimulating agents.

Renal Anemia
🧪

EPO Induction Assays

Quantify secreted erythropoietin in Hep3B, renal epithelial and HUVEC models to profile HIF-PH inhibitor potency.

EPO / HRE
🧬

Hypoxia Signaling

Probe HIF-α stabilization, the VHL ubiquitin ligase axis and cellular oxygen sensing in normoxic conditions.

HIF Pathway
🔴

Erythropoiesis

Study red blood cell maturation, hemoglobin synthesis and erythroid progenitor survival regulated by HIF.

Hematology
❤️

Ischemia & Cardioprotection

Model tissue oxygen-sensing, ischemic preconditioning and myocardial / neuronal protection via HIF activation.

Ischemia
🎗️

Tumor Hypoxia

Investigate HIF modulation of tumor oxygen response, metabolism and radiotherapy sensitization.

Oncology
🛡️

Inflammation & Immunity

Explore immunomodulatory effects of HIF-PH inhibition on mesenchymal stromal and immune cells.

Immunology
💊

Drug Metabolism

Study HIF-driven induction of metabolic enzymes (e.g., CYP, glucose handling) and oxygen-linked physiology.

Metabolism
🩹

Wound Healing & Angiogenesis

Assess VEGF and vascular adaptation pathways downstream of stabilized HIF transcription factors.

Angiogenesis

Key Publications

Foundational studies characterizing Vadasustat (AKB-6548) pharmacology and clinical translation

Pergola RL, et al. Vadadustat, a novel oral HIF stabilizer, provides effective anemia treatment in nondialysis-dependent chronic kidney disease. Kidney Int. 2016;90(5):1115-1122.
doi: 10.1016/j.kint.2016.06.030
Zuk A, Si Z, Loi S, et al. Preclinical characterization of vadadustat (AKB-6548), an oral small molecule hypoxia-inducible factor prolyl-4-hydroxylase inhibitor, for the potential treatment of renal anemia. J Pharmacol Exp Ther. 2022;383(1):11-24.
doi: 10.1124/jpet.122.001328
Macdougall IC, et al. Vadadustat for the treatment of anemia in patients undergoing dialysis (INNO2VATE): a phase 3, multicentre, randomized study. (Phase 3 clinical program).
ClinicalTrials.gov identifier: NCT02892149
Akizawa T, et al. Vadadustat, an oral HIF-PH inhibitor, in Japanese anemic patients with chronic kidney disease — phase 2/3 dose-finding and maintenance studies. Nephron. 2019;143(1):25-34.
doi: 10.1159/000494904
Besarab A, et al. Oral hypoxia-inducible factor prolyl hydroxylase inhibitor vadadustat in anemia of chronic kidney disease: integrated phase 3 efficacy and safety analysis. (Integrated analysis).
doi: 10.1093/ndt/gfab189

Vadasustat Pack Sizes & Ordering Information

Research-grade Vadasustat / AKB-6548 (CAS 1000025-07-9) supplied in 1g / 5g / 10g / 100g / 1KG with full QC documentation; custom bulk quantities supported

TierPack SizeStock StatusSuitable ForShipping & Lead Time
Standard1 gIn StockHIF-PH enzymatic assays, EPO-induction reporter screens, cell-based HIF stabilization studiesAmbient shipping with ice pack; same/next-day dispatch
Medium5 gIn StockRenal anemia models, combination matrices, hypoxia-signaling dose-response programmesCold-chain or ambient; same/next-day dispatch
Large10 gIn StockLong-term in vivo studies, multi-lab consortia, compound library restockingCold-chain shipping; same/next-day dispatch
Bulk100 gIn StockFormulation development, toxicology batches, reference standardsInsulated carton with COA; quote to confirm dispatch
Industrial1 KGMade to orderPilot and production scale, CMO/CDMO supply, process validation campaignsDrum shipment with batch COA; scheduled batch delivery

💡 Reference pack sizes shown above; for exact pricing, lot availability and bulk Vadasustat (AKB-6548) supply please contact us for a quote. Tiered discounts apply to bulk orders.

Frequently Asked Questions (FAQ)

What is Vadasustat (AKB-6548, CAS 1000025-07-9)?
Vadasustat, also known as AKB-6548 or PG-1016548, is a synthetic small molecule (C14H11ClN2O4, MW 306.70) and a potent, orally active inhibitor of hypoxia-inducible factor prolyl-hydroxylases (HIF-PH, also called PHD or EGLN enzymes). By stabilizing HIF-1α and HIF-2α it stimulates endogenous erythropoietin production. It is a leading clinical candidate for anemia associated with chronic kidney disease (CKD).
How does Vadasustat inhibit HIF-PH enzymes?
HIF prolyl-hydroxylases are Fe²⁺- and 2-oxoglutarate (2-OG)-dependent dioxygenases. Vadasustat binds the enzyme active site, chelates the catalytic Fe²⁺ ion and competes with 2-OG, blocking oxidation of specific prolyl residues (Pro402 and Pro564) on HIF-α subunits. This prevents the modification required for recognition by the VHL E3 ubiquitin ligase.
Which HIF-PH isoforms does Vadasustat target?
Vadasustat inhibits all three HIF prolyl-hydroxylases — HIF-PH1 / PHD1 / EGLN2, HIF-PH2 / PHD2 / EGLN1, and HIF-PH3 / PHD3 / EGLN3. Reported Ki values are 0.19 nM, 0.26 nM and 0.56 nM for HIF-PH1, HIF-PH2 and HIF-PH3 respectively, making it a broadly active HIF-PH inhibitor.
What downstream effects result from HIF stabilization by Vadasustat?
Inhibiting HIF-PH causes HIF-α to escape VHL-mediated ubiquitination and degradation, accumulate in the nucleus, dimerize with ARNT (HIF-β) and bind hypoxia response elements (HREs). This upregulates erythropoietin (EPO), transferrin, vascular endothelial growth factor and hundreds of hypoxia-adaptive genes, promoting red blood cell production and tissue oxygen-sensing responses.
Why is Vadasustat being developed for anemia of chronic kidney disease?
In CKD, impaired EPO production and disrupted oxygen sensing contribute to anemia. By stabilizing HIF and inducing endogenous EPO, Vadasustat raises hemoglobin and red blood cell indices without reliance on exogenous erythropoiesis-stimulating agents. It has been studied in Phase III trials (e.g., INNO2VATE) in both dialysis and non-dialysis CKD patients.
How does Vadasustat compare with Roxadustat and Daprodustat?
Roxadustat, daprodustat and vadasustat are all oral HIF-PH inhibitors developed for CKD anemia, but differ in chemical scaffold, isoform selectivity, pharmacokinetics and dosing. Roxadustat (FG-4592) is the most clinically advanced and approved in several regions, while vadasustat (AKB-6548) is notable for its selective induction of EPO over VEGF and its titratable once-daily oral profile. Each is a distinct useful probe for hypoxia-pathway research.
How should Vadasustat (AKB-6548) be dissolved for biological assays?
Vadasustat is soluble in DMSO (approximately 2 mg/mL for stock solutions), DMF (about 5 mg/mL) and ethanol (about 2 mg/mL); it also dissolves in 0.1N NaOH aqueous solution. Prepare a concentrated DMSO or DMF stock, aliquot and store at -20°C protected from light, and dilute into aqueous assay media keeping final organic solvent low (typically below 0.1% v/v).
Is Vadasustat used in research areas beyond CKD anemia?
Yes. Beyond anemia, HIF-PH inhibitors are studied in hypoxia signaling, ischemia / cardioprotection, tumor hypoxia and radiotherapy sensitization, wound healing, inflammatory and immunomodulatory pathways, and as tools to model oxygen sensing. Vadasustat's clean HIF-stabilizing profile makes it a valuable probe across these fields.
Is a Certificate of Analysis (COA) provided with Vadasustat?
Yes. Every batch of research-grade Vadasustat (CAS 1000025-07-9) ships with a Certificate of Analysis reporting HPLC purity of at least 98%, NMR structural confirmation, mass spectrometry, melting point, loss on drying and appearance. MSDS/SDS, residual solvent data and Certificates of Origin are available on request. Please contact us.
What pack sizes and stock status are available?
Vadasustat (AKB-6548) is supplied in 1 g, 5 g, 10 g and 100 g pack sizes (all In Stock) and a 1 KG industrial tier (Made to order). Bulk quantities qualify for tiered pricing — contact Nutrabiotech Chem with your target quantity and specification for a quotation.

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Research-grade Vadasustat / AKB-6548 (CAS 1000025-07-9) — purity ≥98%, COA included
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Weight 1 g

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