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Details

Stereochemistry ACHIRAL
Molecular Formula C19H16N6O4S
Molecular Weight 424.433
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of ZIBOTENTAN

SMILES

COC1=NC(C)=CN=C1NS(=O)(=O)C2=C(N=CC=C2)C3=CC=C(C=C3)C4=NN=CO4

InChI

InChIKey=FJHHZXWJVIEFGJ-UHFFFAOYSA-N
InChI=1S/C19H16N6O4S/c1-12-10-21-17(19(23-12)28-2)25-30(26,27)15-4-3-9-20-16(15)13-5-7-14(8-6-13)18-24-22-11-29-18/h3-11H,1-2H3,(H,21,25)

HIDE SMILES / InChI

Molecular Formula C19H16N6O4S
Molecular Weight 424.433
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Description
Curator's Comment: Description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/15956965 | https://www.ncbi.nlm.nih.gov/pubmed/19065106

Zibotentan (ZD4054) is a potent and specific orally available endothelin A (ETA) receptor antagonist, with no measurable affinity for endothelin B receptor. Activation of the ETA receptor by ET-1 has emerged as an important factor promoting tumor cell proliferation, survival, angiogenesis, migration, invasion, and metastasis in several tumor types. Zibotentan inhibits endothelin-mediated mechanisms that promote tumour cell proliferation. Zibotentan was being developed by AstraZeneca as treatment for heart failure, hormone resistant prostate cancer and other cancers including non-small cell lung, ovarian and breast cancer. However, following disappointing results from a phase III trial in patients with advanced prostate cancer, AstraZeneca decided to discontinue the development of zibotentan as a potential treatment for cancer. AstraZeneca undertook preclinical studies in the UK with zibotentan to investigate its potential as a treatment for heart failure. However, development for this indication has been discontinued.

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
8.27 null [pIC50]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Unknown

Approved Use

Unknown
Primary
Unknown

Approved Use

Unknown
Primary
Unknown

Approved Use

Unknown
Primary
Unknown

Approved Use

Unknown
Primary
Unknown

Approved Use

Unknown
Primary
Unknown

Approved Use

Unknown
Doses

Doses

DosePopulationAdverse events​
22.5 mg 1 times / day multiple, oral
Highest studied dose
Dose: 22.5 mg, 1 times / day
Route: oral
Route: multiple
Dose: 22.5 mg, 1 times / day
Sources: Page: p.5
unhealthy, ADULT
n = 3
Health Status: unhealthy
Condition: prostate cancer
Age Group: ADULT
Sex: M
Food Status: UNKNOWN
Population Size: 3
Sources: Page: p.5
DLT: Peripheral edema, Intraventricular hemorrhage...
Dose limiting toxicities:
Peripheral edema (grade 3, 33.3%)
Intraventricular hemorrhage (grade 3, 33.3%)
Headache (grade 3, 33.3%)
Dyspnea (grade 3, 33.3%)
Sources: Page: p.5
15 mg 1 times / day multiple, oral
Studied dose
Dose: 15 mg, 1 times / day
Route: oral
Route: multiple
Dose: 15 mg, 1 times / day
Sources: Page: p.5
unhealthy, ADULT
n = 10
Health Status: unhealthy
Condition: cancer
Age Group: ADULT
Sex: M
Food Status: UNKNOWN
Population Size: 10
Sources: Page: p.5
AEs

AEs

AESignificanceDosePopulation
Dyspnea grade 3, 33.3%
DLT, Disc. AE
22.5 mg 1 times / day multiple, oral
Highest studied dose
Dose: 22.5 mg, 1 times / day
Route: oral
Route: multiple
Dose: 22.5 mg, 1 times / day
Sources: Page: p.5
unhealthy, ADULT
n = 3
Health Status: unhealthy
Condition: prostate cancer
Age Group: ADULT
Sex: M
Food Status: UNKNOWN
Population Size: 3
Sources: Page: p.5
Headache grade 3, 33.3%
DLT, Disc. AE
22.5 mg 1 times / day multiple, oral
Highest studied dose
Dose: 22.5 mg, 1 times / day
Route: oral
Route: multiple
Dose: 22.5 mg, 1 times / day
Sources: Page: p.5
unhealthy, ADULT
n = 3
Health Status: unhealthy
Condition: prostate cancer
Age Group: ADULT
Sex: M
Food Status: UNKNOWN
Population Size: 3
Sources: Page: p.5
Intraventricular hemorrhage grade 3, 33.3%
DLT, Disc. AE
22.5 mg 1 times / day multiple, oral
Highest studied dose
Dose: 22.5 mg, 1 times / day
Route: oral
Route: multiple
Dose: 22.5 mg, 1 times / day
Sources: Page: p.5
unhealthy, ADULT
n = 3
Health Status: unhealthy
Condition: prostate cancer
Age Group: ADULT
Sex: M
Food Status: UNKNOWN
Population Size: 3
Sources: Page: p.5
Peripheral edema grade 3, 33.3%
DLT, Disc. AE
22.5 mg 1 times / day multiple, oral
Highest studied dose
Dose: 22.5 mg, 1 times / day
Route: oral
Route: multiple
Dose: 22.5 mg, 1 times / day
Sources: Page: p.5
unhealthy, ADULT
n = 3
Health Status: unhealthy
Condition: prostate cancer
Age Group: ADULT
Sex: M
Food Status: UNKNOWN
Population Size: 3
Sources: Page: p.5
Sourcing

Sourcing

Vendor/AggregatorIDURL
PubMed

PubMed

TitleDatePubMed
Specific inhibition of the endothelin A receptor with ZD4054: clinical and pre-clinical evidence.
2005 Jun 20
Emerging therapies in castrate-resistant prostate cancer.
2009 May
Critical appraisal of cabazitaxel in the management of advanced prostate cancer.
2010 Dec 3
An open-label, randomized, single-center, two-period, phase I, crossover study of the effect of zibotentan (ZD4054) on the pharmacokinetics of midazolam in healthy male volunteers.
2010 Jul
Zibotentan for the treatment of castrate-resistant prostate cancer.
2010 Jul
Gateways to clinical trials.
2010 Nov
Pharmacokinetic and tolerability profile of once-daily zibotentan (ZD4054) in Japanese and Caucasian patients with hormone-resistant prostate cancer.
2010 Nov
Final safety and efficacy analysis of the specific endothelin A receptor antagonist zibotentan (ZD4054) in patients with metastatic castration-resistant prostate cancer and bone metastases who were pain-free or mildly symptomatic for pain: a double-blind, placebo-controlled, randomized Phase II trial.
2010 Oct
Patents

Sample Use Guides

Patients with metastatic, castrate-resistant prostate cancer (CRPC) were treated with escalating doses of oral zibotentan (ZD4054) 10-200 mg once daily. The maximum well-tolerated dose was 15 mg orally daily.
Route of Administration: Oral
In the human ovarian cancer ET(A)R-positive cell lines HEY, OVCA 433, SKOV-3, and A-2780, 1 uM Zibotentan (ZD4054) effectively inhibited the basal and ET-1-induced cell proliferation, associated with the inhibition of AKT and p42/44MAPK phosphorylation, and with increased apoptosis, through the inhibition of bcl-2 and activation of caspase-3 and poly(ADP-ribose) polymerase proteins.
Substance Class Chemical
Created
by admin
on Fri Dec 15 15:59:09 GMT 2023
Edited
by admin
on Fri Dec 15 15:59:09 GMT 2023
Record UNII
8054MM4902
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
ZIBOTENTAN
INN   JAN   MART.   MI   USAN   WHO-DD  
INN   USAN  
Official Name English
N-(3-METHOXY-5-METHYLPYRAZIN-2-YL)-2-(4-(1,3,4-OXADIAZOL-2-YL)PHENYL)PRIDINE-3-SULFONAMIDE
Common Name English
Zibotentan [WHO-DD]
Common Name English
3-PYRIDINESULFONAMIDE, N-(3-METHOXY-5-METHYL-2-PYRAZINYL)-2-(4-(1,3,4-OXADIAZOL-2-YL)PHENYL)-
Systematic Name English
ZIBOTENTAN [JAN]
Common Name English
ZD4054
Code English
N-(3-Methoxy-5-methylpyrazin-2-yl)-2-[4-(1,3,4-oxadiazol-2-yl)phenyl]pyridine-3-sulfonamide
Systematic Name English
ZD-4054
Code English
ZIBOTENTAN [USAN]
Common Name English
ZIBOTENTAN [MART.]
Common Name English
zibotentan [INN]
Common Name English
ZIBOTENTAN [MI]
Common Name English
Code System Code Type Description
ChEMBL
CHEMBL1628688
Created by admin on Fri Dec 15 15:59:09 GMT 2023 , Edited by admin on Fri Dec 15 15:59:09 GMT 2023
PRIMARY
FDA UNII
8054MM4902
Created by admin on Fri Dec 15 15:59:09 GMT 2023 , Edited by admin on Fri Dec 15 15:59:09 GMT 2023
PRIMARY
DRUG BANK
DB06629
Created by admin on Fri Dec 15 15:59:09 GMT 2023 , Edited by admin on Fri Dec 15 15:59:09 GMT 2023
PRIMARY
INN
8664
Created by admin on Fri Dec 15 15:59:09 GMT 2023 , Edited by admin on Fri Dec 15 15:59:09 GMT 2023
PRIMARY
MERCK INDEX
m11590
Created by admin on Fri Dec 15 15:59:09 GMT 2023 , Edited by admin on Fri Dec 15 15:59:09 GMT 2023
PRIMARY Merck Index
CAS
186497-07-4
Created by admin on Fri Dec 15 15:59:09 GMT 2023 , Edited by admin on Fri Dec 15 15:59:09 GMT 2023
PRIMARY
EVMPD
SUB32097
Created by admin on Fri Dec 15 15:59:09 GMT 2023 , Edited by admin on Fri Dec 15 15:59:09 GMT 2023
PRIMARY
WIKIPEDIA
ZIBOTENTAN
Created by admin on Fri Dec 15 15:59:09 GMT 2023 , Edited by admin on Fri Dec 15 15:59:09 GMT 2023
PRIMARY
EPA CompTox
DTXSID70870171
Created by admin on Fri Dec 15 15:59:09 GMT 2023 , Edited by admin on Fri Dec 15 15:59:09 GMT 2023
PRIMARY
PUBCHEM
9910224
Created by admin on Fri Dec 15 15:59:09 GMT 2023 , Edited by admin on Fri Dec 15 15:59:09 GMT 2023
PRIMARY
SMS_ID
100000124399
Created by admin on Fri Dec 15 15:59:09 GMT 2023 , Edited by admin on Fri Dec 15 15:59:09 GMT 2023
PRIMARY
MESH
C511404
Created by admin on Fri Dec 15 15:59:09 GMT 2023 , Edited by admin on Fri Dec 15 15:59:09 GMT 2023
PRIMARY
NCI_THESAURUS
C48430
Created by admin on Fri Dec 15 15:59:09 GMT 2023 , Edited by admin on Fri Dec 15 15:59:09 GMT 2023
PRIMARY
USAN
UU-90
Created by admin on Fri Dec 15 15:59:09 GMT 2023 , Edited by admin on Fri Dec 15 15:59:09 GMT 2023
PRIMARY
Related Record Type Details
TARGET -> INHIBITOR
Related Record Type Details
ACTIVE MOIETY