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Details

Stereochemistry ACHIRAL
Molecular Formula C19H27N3O6
Molecular Weight 393.4342
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of DAPRODUSTAT

SMILES

OC(=O)CNC(=O)C1C(=O)N(C2CCCCC2)C(=O)N(C3CCCCC3)C1=O

InChI

InChIKey=RUEYEZADQJCKGV-UHFFFAOYSA-N
InChI=1S/C19H27N3O6/c23-14(24)11-20-16(25)15-17(26)21(12-7-3-1-4-8-12)19(28)22(18(15)27)13-9-5-2-6-10-13/h12-13,15H,1-11H2,(H,20,25)(H,23,24)

HIDE SMILES / InChI

Molecular Formula C19H27N3O6
Molecular Weight 393.4342
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Description
Curator's Comment: The description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/28928122 | https://www.ncbi.nlm.nih.gov/pubmed/27978511

Daprodustat (GSK1278863) is a low nanomolar hypoxia-inducible factor (HIF) prolyl hydroxylase (PHD) inhibitor, that increases HIF stability and action. In preclinical studies, Daprodustat stabilizes HIFα in cell lines, resulting in the production of increased levels of erythropoietin (EPO). In normal mice, a single dose of Daprodustat induced significant increases in circulating plasma EPO but only minimal increases in plasma vascular endothelial growth factor (VEGF-A) concentrations. Daprodustat significantly increased reticulocytes and red cell mass parameters in pre-clinical species following once-daily oral administration and has demonstrated an acceptable nonclinical toxicity profile supporting continued clinical development. In a phase 1 study, Daprodustat was well tolerated and increased erythropoietin (EPO) levels in apparently healthy individuals proportional to dose. In phase 2a studies in non–dialysis-dependent chronic kidney disease (NDD CKD) and end-stage renal disease Daprodustat 4-10 mg once-daily produced the dose-dependent increase in hemoglobin relative to placebo. The Phase III programme for the drug includes two studies evaluating its safety and efficacy compared to recombinant human erythropoietin in dialysis-dependent subjects with anemia associated with CKD (ASCEND-D) and in non-dialysis dependent patients with the condition (ASCEND-ND).

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
3.5 nM [IC50]
22.2 nM [IC50]
5.5 nM [IC50]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Unknown

Approved Use

Unknown
OverviewDrug as perpetrator​

Drug as perpetrator​

TargetModalityActivityMetaboliteClinical evidence
no
no
no
no
no
no
no
no
no
no
no
no
no
no
no
no
no
no
no
no
no
no
no
no
no
no
no
no
no
no
no
no
no
no
no
no
no
no
no
no
no
no
no
no
no
no
no
no
no
no
no
no
no
yes [IC50 11 uM]
yes [IC50 21 uM]
yes [IC50 6 uM]
Drug as victim

Drug as victim

TargetModalityActivityMetaboliteClinical evidence
major
yes (co-administration study)
Comment: Gemfibrozil increased Cmax and AUCinf by 3.9-fold and 18.6-fold.
Page: 71.0
minor
no
no
no
no
no
no
no
no
no
no
no
no
no
no
no
no
no
no
no
no
no
no
no
no
weak
weak
yes
yes
yes
yes
yes
yes
Tox targets
Sourcing

Sourcing

Vendor/AggregatorIDURL
PubMed

PubMed

TitleDatePubMed
Targeting the hypoxia-sensing pathway in clinical hematology.
2014 Feb
Patents

Patents

Sample Use Guides

0.5, 2, and 5 mg once-daily for 4-week treatment
Route of Administration: Oral
Human CP4H/Cofactor mix (4X final concentration in 50 mM HEPES, pH 7.5 with 50 mM KCl) was incubated at room temperature for 30 minutes with GSK1278863 (10 point, 3-fold serial dilution in 50% DMSO, 15X final concentration) or 50% DMSO. Substrate mix (1.4X final concentration in 50 mM HEPES, pH 7.5 with 50 mM KCl) was added to the plate yielding a 32 μL final reaction volume. After 20 minutes, the reaction was quenched by the addition of 0.67% final H3PO4. Product formation was detected using Reverse Phase High Performance Liquid Chromatography (HPLC; Ex 336nM and Em 517 nM). Final concentrations of the CP4H/Cofactor mix were 21.11 nM enzyme, 1 mg/mL BSA, 50 μM FeCl2, 2 mM ascorbic acid, 100 μM DTT, and 100 μg/mL catalase. The substrate mix consisted of 100 μM dansyl-GFPG-Oet, and 110 μM α-ketoglutarate. Percent inhibition data were determined from the ratio of product to substrate after a 20 minute reaction. The IC50 value was determined by fitting the percent inhibition data to a two-parameter IC50 equation.
Substance Class Chemical
Created
by admin
on Sat Dec 16 16:54:58 UTC 2023
Edited
by admin
on Sat Dec 16 16:54:58 UTC 2023
Record UNII
JVR38ZM64B
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
DAPRODUSTAT
INN   USAN   WHO-DD  
USAN   INN  
Official Name English
Daprodustat [WHO-DD]
Common Name English
DAPRODUSTAT [JAN]
Common Name English
daprodustat [INN]
Common Name English
GLYCINE, N-((1,3-DICYCLOHEXYLHEXAHYDRO-2,4,6-TRIOXO-5-PYRIMIDINYL)CARBONYL)-
Systematic Name English
DAPRODUSTAT [USAN]
Common Name English
N-[(1,3-Dicyclohexylhexahydro-2,4,6-trioxopyrimidin-5-yl)carbonyl]glycine
Systematic Name English
GSK1278863
Code English
JESDUVROQ
Brand Name English
GSK-1278863
Code English
Code System Code Type Description
WIKIPEDIA
Daprodustat
Created by admin on Sat Dec 16 16:54:58 UTC 2023 , Edited by admin on Sat Dec 16 16:54:58 UTC 2023
PRIMARY
DAILYMED
JVR38ZM64B
Created by admin on Sat Dec 16 16:54:58 UTC 2023 , Edited by admin on Sat Dec 16 16:54:58 UTC 2023
PRIMARY
DRUG BANK
DB11682
Created by admin on Sat Dec 16 16:54:58 UTC 2023 , Edited by admin on Sat Dec 16 16:54:58 UTC 2023
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FDA UNII
JVR38ZM64B
Created by admin on Sat Dec 16 16:54:58 UTC 2023 , Edited by admin on Sat Dec 16 16:54:58 UTC 2023
PRIMARY
EPA CompTox
DTXSID501337360
Created by admin on Sat Dec 16 16:54:58 UTC 2023 , Edited by admin on Sat Dec 16 16:54:58 UTC 2023
PRIMARY
EVMPD
SUB185070
Created by admin on Sat Dec 16 16:54:58 UTC 2023 , Edited by admin on Sat Dec 16 16:54:58 UTC 2023
PRIMARY
USAN
BC-163
Created by admin on Sat Dec 16 16:54:58 UTC 2023 , Edited by admin on Sat Dec 16 16:54:58 UTC 2023
PRIMARY
PUBCHEM
91617630
Created by admin on Sat Dec 16 16:54:58 UTC 2023 , Edited by admin on Sat Dec 16 16:54:58 UTC 2023
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INN
10167
Created by admin on Sat Dec 16 16:54:58 UTC 2023 , Edited by admin on Sat Dec 16 16:54:58 UTC 2023
PRIMARY
NCI_THESAURUS
C169877
Created by admin on Sat Dec 16 16:54:58 UTC 2023 , Edited by admin on Sat Dec 16 16:54:58 UTC 2023
PRIMARY
CAS
960539-70-2
Created by admin on Sat Dec 16 16:54:58 UTC 2023 , Edited by admin on Sat Dec 16 16:54:58 UTC 2023
PRIMARY
ChEMBL
CHEMBL3544988
Created by admin on Sat Dec 16 16:54:58 UTC 2023 , Edited by admin on Sat Dec 16 16:54:58 UTC 2023
PRIMARY
SMS_ID
100000170880
Created by admin on Sat Dec 16 16:54:58 UTC 2023 , Edited by admin on Sat Dec 16 16:54:58 UTC 2023
PRIMARY
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TARGET -> INHIBITOR
TARGET -> INHIBITOR
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ACTIVE MOIETY