| 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
SMILES
COC1=NC(C)=CN=C1NS(=O)(=O)C2=CC=CN=C2C3=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)
| Molecular Formula | C19H16N6O4S |
| Molecular Weight | 424.433 |
| Charge | 0 |
| Count |
MOL RATIO
1 MOL RATIO (average) |
| Stereochemistry | ACHIRAL |
| Additional Stereochemistry | No |
| Defined Stereocenters | 0 / 0 |
| E/Z Centers | 0 |
| Optical Activity | NONE |
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.
Originator
Approval Year
Doses
AEs
Sourcing
PubMed
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.
