Details
Stereochemistry | ACHIRAL |
Molecular Formula | C14H11ClN2O4 |
Molecular Weight | 306.701 |
Optical Activity | NONE |
Defined Stereocenters | 0 / 0 |
E/Z Centers | 0 |
Charge | 0 |
SHOW SMILES / InChI
SMILES
OC(=O)CNC(=O)C1=C(O)C=C(C=N1)C2=CC=CC(Cl)=C2
InChI
InChIKey=JGRXMPYUTJLTKT-UHFFFAOYSA-N
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)
Vadadustat is an Hypoxia-inducible factor (HIF) prolyl hydroxylase (PH) enzyme inhibitor. Patients with chronic kidney disease (CKD) have reduced levels of erythropoietin (EPO) and iron in the body, which can result in decreased number of oxygen-carrying red blood cells (RBCs) (anemia). The deficiency in RBCs causes inadequate oxygen delivery to cells and tissues. Vadadustat simulates the hypoxia response pathway by stabilizing key regulatory proteins called HIFs. Under normal conditions, when sufficient oxygen is present, HIF proteins are targeted for degradation by HIF-PH to maintain homeostasis in RBC production. Under conditions of hypoxia, HIF-PH activity is reduced, resulting in HIF stabilization. Stable HIF moves to the nucleus, where it activates target genes that increase EPO synthesis, resulting in the production of new RBCs, and suppression of hepcidin to promote iron absorption and mobilization. Vadadustat is currently in the phase 3 stage of development for the treatment of anemia secondary to CKD.
Originator
Approval Year
Targets
Primary Target | Pharmacology | Condition | Potency |
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Target ID: CHEMBL3831261: Hypoxia-inducible factor prolyl hydroxylase Sources: http://akebia.com/programs/vadadustat/moa/ |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
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Primary | Unknown Approved UseUnknown |
Cmax
Value | Dose | Co-administered | Analyte | Population |
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27.9 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/38924087/ |
300 mg single, oral dose: 300 mg route of administration: Oral experiment type: SINGLE co-administered: |
VADADUSTAT plasma | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED |
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59.6 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/38924087/ |
900 mg 1 times / day multiple, oral dose: 900 mg route of administration: Oral experiment type: MULTIPLE co-administered: |
VADADUSTAT plasma | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED |
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53.7 μg/mL |
600 mg single, oral dose: 600 mg route of administration: Oral experiment type: SINGLE co-administered: |
VADADUSTAT plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
AUC
Value | Dose | Co-administered | Analyte | Population |
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190 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/38924087/ |
300 mg single, oral dose: 300 mg route of administration: Oral experiment type: SINGLE co-administered: |
VADADUSTAT plasma | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED |
|
556.4 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/38924087/ |
900 mg 1 times / day multiple, oral dose: 900 mg route of administration: Oral experiment type: MULTIPLE co-administered: |
VADADUSTAT plasma | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED |
|
395 μg × h/mL |
600 mg single, oral dose: 600 mg route of administration: Oral experiment type: SINGLE co-administered: |
VADADUSTAT plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
T1/2
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
4.7 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/38924087/ |
300 mg single, oral dose: 300 mg route of administration: Oral experiment type: SINGLE co-administered: |
VADADUSTAT plasma | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED |
|
4.6 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/38924087/ |
900 mg 1 times / day multiple, oral dose: 900 mg route of administration: Oral experiment type: MULTIPLE co-administered: |
VADADUSTAT plasma | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED |
|
4.95 h |
600 mg single, oral dose: 600 mg route of administration: Oral experiment type: SINGLE co-administered: |
VADADUSTAT plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
Funbound
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
0.5% |
unknown |
VADADUSTAT plasma | Homo sapiens population: UNKNOWN age: UNKNOWN sex: UNKNOWN food status: UNKNOWN |
Sample Use Guides
In Vivo Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/28343225
A phase 2a, multicenter, randomized, double-blind, placebo-controlled, dose-ranging trial (NCT01381094) was undertaken in adults with anemia secondary to chronic kidney disease stage 3 or 4. Eligible subjects were evenly randomized to 5 groups: 240, 370, 500, or 630 mg of once-daily oral vadadustat or placebo for 6 weeks.
Route of Administration:
Oral
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C78275
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NCI_THESAURUS |
C471
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CD-55
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I60W9520VV
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C152811
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DB12255
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100000172788
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Vadadustat
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ACTIVE MOIETY