WARNING: This product is for research use only, not for human or veterinary use.
MedKoo CAT#: 319561
CAS#: 1000025-07-9
Description: Vadadustat, also known as AKB-6548 and PG-1016548, is a potent Hypoxia-inducible factor-proline dioxygenase inhibitor. AKB-6548 works by inhibiting hypoxia inducible factor-prolyl hydroxylase (HIP-PH), leading to stabilization and increased levels of HIFα. In turn HIFα improves production of hemoglobin and red blood cells (RBCs), while maintaining normal levels of erythropoietin (EPO) in patients. We believe this differentiated mechanism of action has the potential to be safer than that of injectable recombinant erythropoietin stimulating agents (rESAs), avoiding supra-physiological levels of EPO and saturation of EPO receptors for prolonged periods of time.
MedKoo Cat#: 319561
Name: Vadadustat
CAS#: 1000025-07-9
Chemical Formula: C14H11ClN2O4
Exact Mass: 306.0407
Molecular Weight: 306.7
Elemental Analysis: C, 54.83; H, 3.62; Cl, 11.56; N, 9.13; O, 20.87
Synonym: AKB-6548; AKB 6548; AKB6548; PG-1016548; PG 1016548; PG1016548; B-506; B506; Vadadustat
IUPAC/Chemical Name: (5-(3-chlorophenyl)-3-hydroxypicolinoyl)glycine
InChi Key: JGRXMPYUTJLTKT-UHFFFAOYSA-N
InChi Code: InChI=1S/C14H11ClN2O4/c15-10-3-1-2-8(4-10)9-5-11(18)13(16-6-9)14(21)17-7-12(19)20/h1-6,18H,7H2,(H,17,21)(H,19,20)
SMILES Code: O=C(O)CNC(C1=NC=C(C2=CC=CC(Cl)=C2)C=C1O)=O
Appearance: White to off-white solid powder.
Purity: >98% (or refer to the Certificate of Analysis)
Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility: Soluble in DMSO, not in water
Shelf Life: >2 years if stored properly
Drug Formulation: This drug may be formulated in DMSO
Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code: 2934.99.9001
| Biological target: | Vadadustat (PG-1016548) is a titratable, oral hypoxia-inducible factor prolyl hydroxylase (HIF-PH) inhibitor. |
| In vitro activity: | This research has shown that Vadadustat pretreatment enhances the immunosuppressive potential of MSCs. Vadadustat significantly enhanced the suppressive effect of MSCs on PBMCs proliferation (MLR test), and this effect was partially associated with the modulation of MSCs secretome. However, the suppressive capacity of MSCs was higher in direct contact with PBMCs. This may indicate that changes in both, compounds secreted by MSCs and presented on their surface are responsible for enhancing the immunosuppressive effect of MSCs pretreated with Vadadustat. Moreover, Vadadustat significantly diminished the chemotactic properties of the MSCs secretome, as assessed by the monocyte-enriched PBMCs migration assay. Reference: Cells. 2020 Nov; 9(11): 2396. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7693843/ |
| In vivo activity: | In the non-CKD model, in which the mice were not anemic, vadadustat induced similar increases in hemoglobin concentrations from pretreatment values in the WT and EKO groups (Supplementary Figure S1). In the CKD model, as expected, both WT and EKO groups developed moderate anemia (Figure 1a and b). Vadadustat normalized red blood cell counts and hemoglobin concentrations in both the WT and EKO CKD groups (Figure 1a and b). In the CKD models, whereas 3 weeks of vehicle treatment resulted in a mean 1.5 to 2.1 g/dl decrease in hemoglobin concentrations, 3 weeks of vadadustat treatment resulted in a mean 3.4 to 4.5 g/dl increase in hemoglobin concentrations (Figure 1c, Supplementary Figure S2). Vadadustat also increased hematocrit (Figure 1d), mean corpuscular volume (Figure 1e), mean corpuscular hemoglobin (Figure 1f), and red blood cell distribution width (Figure 1g) in both the WT and EKO CKD groups. Therefore, vadadustat ameliorated CKD-associated anemia in the presence or absence of ERFE, demonstrating ERFE-independent proerythropoietic effects. Reference: Kidney Int. 2021 Jul;100(1):79-89. https://www.kidney-international.org/article/S0085-2538(21)00354-9/fulltext |
| Solvent | Max Conc. mg/mL | Max Conc. mM | |
|---|---|---|---|
| Solubility | |||
| DMSO | 54.33 | 177.14 | |
| DMF | 5.0 | 16.3 | |
| DMF:PBS (pH 7.2) (1:20) | 0.04 | 0.13 | |
| Ethanol | 5.5 | 17.93 |
The following data is based on the product molecular weight 306.7 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.
| Concentration / Solvent Volume / Mass | 1 mg | 5 mg | 10 mg |
|---|---|---|---|
| 1 mM | 1.15 mL | 5.76 mL | 11.51 mL |
| 5 mM | 0.23 mL | 1.15 mL | 2.3 mL |
| 10 mM | 0.12 mL | 0.58 mL | 1.15 mL |
| 50 mM | 0.02 mL | 0.12 mL | 0.23 mL |
| Formulation protocol: | 1. Zielniok K, Burdzinska A, Kaleta B, Zagozdzon R, Paczek L. Vadadustat, a HIF Prolyl Hydroxylase Inhibitor, Improves Immunomodulatory Properties of Human Mesenchymal Stromal Cells. Cells. 2020 Nov 1;9(11):2396. doi: 10.3390/cells9112396. PMID: 33139632; PMCID: PMC7693843. 2. Hanudel MR, Wong S, Jung G, Qiao B, Gabayan V, Zuk A, Ganz T. Amelioration of chronic kidney disease-associated anemia by vadadustat in mice is not dependent on erythroferrone. Kidney Int. 2021 Jul;100(1):79-89. doi: 10.1016/j.kint.2021.03.019. Epub 2021 Mar 31. PMID: 33811979. |
| In vitro protocol: | 1. Zielniok K, Burdzinska A, Kaleta B, Zagozdzon R, Paczek L. Vadadustat, a HIF Prolyl Hydroxylase Inhibitor, Improves Immunomodulatory Properties of Human Mesenchymal Stromal Cells. Cells. 2020 Nov 1;9(11):2396. doi: 10.3390/cells9112396. PMID: 33139632; PMCID: PMC7693843. |
| In vivo protocol: | 1. Hanudel MR, Wong S, Jung G, Qiao B, Gabayan V, Zuk A, Ganz T. Amelioration of chronic kidney disease-associated anemia by vadadustat in mice is not dependent on erythroferrone. Kidney Int. 2021 Jul;100(1):79-89. doi: 10.1016/j.kint.2021.03.019. Epub 2021 Mar 31. PMID: 33811979. |
1: Beuck S, Schänzer W, Thevis M. Hypoxia-inducible factor stabilizers and other small-molecule erythropoiesis-stimulating agents in current and preventive doping analysis. Drug Test Anal. 2012 Nov;4(11):830-45. doi: 10.1002/dta.390. Epub 2012 Feb 24. Review. PubMed PMID: 22362605.
