Zibotentan
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Also known as ZD-4054ZD4054SID137275851SID124950684ZIBOTENTAN (ZD4054)
Summary
Zibotentan (CHEMBL1628688) is a phase-3 clinical-stage small-molecule endothelin A receptor antagonist targeting EDNRA; indicated across 14 conditions including prostate adenocarcinoma and non-small cell lung carcinoma.
At a glance
- Status: Max clinical phase 3 (not approved)
- Modality: Small molecule
- Targets: 1 (EDNRA)
- Indications: 14 conditions
- Clinical trials: 32
- Chemistry: 424.4 Da · C19H16N6O4S
Identifiers
Drug identity and classification
| Field | Value |
|---|---|
| ChEMBL ID | CHEMBL1628688 |
| Name | Zibotentan |
| Type | Small molecule |
| Max phase | 3 |
| FDA approved | no |
| PubChem CID | 9910224 |
| ChEBI | CHEBI:94573 |
| Molecular formula | C19H16N6O4S |
| Molecular weight | 424.4 |
| InChIKey | FJHHZXWJVIEFGJ-UHFFFAOYSA-N |
SMILES: CC1=CN=C(C(=N1)OC)NS(=O)(=O)C2=C(N=CC=C2)C3=CC=C(C=C3)C4=NN=CO4
IUPAC name: N-(3-methoxy-5-methylpyrazin-2-yl)-2-[4-(1,3,4-oxadiazol-2-yl)phenyl]pyridine-3-sulfonamide
ChEBI definition: A member of the class of pyridinesulfonamides that is benzene substituted by 3-[(3-methoxy-5-methylpyrazin-2-yl)sulfamoyl]pyridin-2-yl and 1,3,4-oxadiazol-2-yl groups at positions 1 and 4, respectively. It is an endothelin A receptor antagonist with potential antineoplastic activity.
Pharmacological roles (ChEBI): endothelin A receptor antagonist, antineoplastic agent, antihypertensive agent.
Also known as: ZD-4054, ZD4054, Zibotentan, ZIBOTENTAN, SID137275851, SID124950684, ZIBOTENTAN (ZD4054), Zibotentan (ZD4054)
Patent coverage: 462 distinct patent families (1,123 SureChEMBL compound mentions), from 3 matched compound structure(s). One matched structure accounts for 947 (84%) of the total. Mentions count patents naming the compound (not distinct inventions), so promiscuous / reference molecules inflate the mention figure — families are the dedup metric.
Targets
Targets
Primary targets (GtoPdb curated mechanism): the Cancer dependency column is the DepMap CRISPR fitness signal (% of screened cell lines dependent on the target).
| Gene | Target | Action | pAffinity | Cancer dependency | UniProt |
|---|---|---|---|---|---|
| EDNRA | ETA receptor | Antagonist | 8.3 | 0.1% | P25101 |
Broader ChEMBL bioactivity targets: 1 (assay-derived). Sample: Endothelin-1 receptor.
Bioactivity
ChEMBL activities: 2 potent at pChembl ≥ 5 of 2 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):
| Target | pChembl | Type | Value | Unit | Activity ID |
|---|---|---|---|---|---|
| EDNRA | 7.89 | Ki | 13 | nM | CHEMBL_ACT_29064078 |
| EDNRA | 7.68 | IC50 | 21 | nM | CHEMBL_ACT_19405753 |
Target pathways
Aggregated over 1 target gene(s): EDNRA.
Top Reactome pathways
2 total, by targets touching each:
| Pathway | Targets | Genes |
|---|---|---|
| Peptide ligand-binding receptors | 1 | EDNRA |
| G alpha (q) signalling events | 1 | EDNRA |
Dominant GO biological processes
| GO term | Targets |
|---|---|
| mitotic cell cycle | 1 |
| branching involved in blood vessel morphogenesis | 1 |
| response to hypoxia | 1 |
| in utero embryonic development | 1 |
| blood vessel remodeling | 1 |
| response to amphetamine | 1 |
| regulation of heart rate | 1 |
| glomerular filtration | 1 |
| cardiac chamber formation | 1 |
| left ventricular cardiac muscle tissue morphogenesis | 1 |
| atrial cardiac muscle tissue development | 1 |
| cardiac neural crest cell migration involved in outflow tract morphogenesis | 1 |
| noradrenergic neuron differentiation | 1 |
| intracellular calcium ion homeostasis | 1 |
| smooth muscle contraction | 1 |
Indications & clinical
Indications
14 indications (0 at ChEMBL trial phase 4). Phase below is the highest clinical-trial phase recorded for this drug against each disease — not the molecule’s overall approval status (that is in the Summary).
| Indication | Trial phase | MONDO | EFO |
|---|---|---|---|
| prostate adenocarcinoma | 2 | MONDO:0005082 | EFO:0000673 |
| non-small cell lung carcinoma | 2 | MONDO:0005233 | EFO:0003060 |
| intermittent vascular claudication | 2 | MONDO:0005295 | EFO:0003876 |
| peripheral arterial disease | 2 | MONDO:0005386 | EFO:0004265 |
| breast neoplasm | 2 | MONDO:0021100 | MONDO:0007254 |
| ovarian cancer | 2 | MONDO:0008170 | MONDO:0008170 |
| chronic kidney disease | 2 | MONDO:0005300 | EFO:0003884 |
| cirrhosis of liver | 2 | MONDO:0005155 | EFO:0001422 |
| colorectal neoplasm | 2 | MONDO:0005335 | MONDO:0005575 |
| lung neoplasm | 2 | MONDO:0021117 | MONDO:0008903 |
| liver disorder | 1 | MONDO:0005154 | EFO:0001421 |
| neoplasm | 1 | MONDO:0005070 | MONDO:0004992 |
2 further indication records had no mapped disease name (EFO/MeSH-only) or were duplicates, and are omitted.
Clinical trials
Total trials: 32.
Phase distribution
| Phase | Trials |
|---|---|
| PHASE2 | 15 |
| PHASE1 | 12 |
| PHASE3 | 4 |
| Not specified | 1 |
Top trials by phase / activity
| NCT | Phase | Status | Title |
|---|---|---|---|
| NCT06087835 | PHASE3 | ACTIVE_NOT_RECRUITING | Study to Investigate Efficacy, Safety, and Tolerability of Zibotentan/Dapagliflozin Compared to Dapagliflozin in Participants With Chronic Kidney Disease and High Proteinuria (ZENITH High Proteinuria) |
| NCT00554229 | PHASE3 | COMPLETED | A Phase III Trial of ZD4054 (Zibotentan) (Endothelin A Antagonist) in Hormone Resistant Prostate Cancer With Bone Metastases |
| NCT00617669 | PHASE3 | COMPLETED | A Phase III Trial of ZD4054 (Zibotentan) (Endothelin A Antagonist) and Docetaxel in Metastatic Hormone Resistant Prostate Cancer |
| NCT00626548 | PHASE3 | TERMINATED | A Phase III Trial of ZD4054 (Zibotentan) (Endothelin A Antagonist) in Non-metastatic Hormone Resistant Prostate Cancer |
| NCT06942910 | PHASE2 | RECRUITING | A Study to Investigate the Effects of Zibotentan/Dapagliflozin Combination Compared to Dapagliflozin Alone in Adult Participants With Chronic Kidney Disease and High Proteinuria |
| NCT00055471 | PHASE2 | COMPLETED | A Phase IIa. Open-label, Multicenter, Dose-escalation Study to Assess the Tolerability and Pharmacokinetics of ZD4054 (Zibotentan) Given Orally Once Daily in Subjects With Metastatic Prostate Cancer |
| NCT00090363 | PHASE2 | COMPLETED | ZD4054 (Zibotentan) in Pain-free or Mildly Symptomatic Patients With Prostate Cancer and Bone Metastases Who Have Rising Serum Prostate Specific Antigen (PSA) |
| NCT00745875 | PHASE2 | COMPLETED | ZD4054 (Zibotentan) Phase II Non-Small Cell Lung Cancer Study |
| NCT00929162 | PHASE2 | TERMINATED | ZD4054 (Zibotentan) or Placebo Plus Chemotherapy in Patients With Advanced Ovarian Cancer |
| NCT01000948 | PHASE2 | TERMINATED | A Safety Study of ZD4054 in Prior Chemotherapy Treated Patients With Metastatic Hormone-resistant Prostate Cancer |
| NCT01119118 | PHASE2 | TERMINATED | ZD4054 With Positron Emission Tomography/Magnetic Resonance Imaging (PET/MRI) for Prostate Cancer |
| NCT01134497 | PHASE2 | WITHDRAWN | Carboplatin With or Without ZD4054 in Patients With Metastatic Breast Cancer |
| NCT01205711 | PHASE2 | COMPLETED | Irinotecan Hydrochloride, Fluorouracil, and Leucovorin Calcium With or Without Zibotentan in Treating Patients With Metastatic Colorectal Cancer |
| NCT01890135 | PHASE2 | COMPLETED | Zibotentan, an Endothelin Receptor Antagonist, Patients With Intermittent Claudication |
| NCT02047708 | PHASE2 | COMPLETED | Zibotentan Better Renal Scleroderma Outcome Study |
| NCT04097314 | PHASE2 | COMPLETED | Precision Medicine With Zibotentan in Microvascular Angina |
| NCT04724837 | PHASE2 | COMPLETED | Zibotentan and Dapagliflozin for the Treatment of CKD (ZENITH-CKD Trial) |
| NCT05570305 | PHASE2 | COMPLETED | Zibotentan and Dapagliflozin in Patients With Type 2 Diabetes and Elevated Albuminuria |
| NCT06269484 | PHASE2 | COMPLETED | A Phase IIb Study to Evaluate the Safety of Zibotentan/Dapagliflozin in Participants With Cirrhosis-ZEAL-UNLOCK |
| NCT00314782 | PHASE1 | COMPLETED | Phase I Study of ZD4054 (Zibotentan) and Docetaxel in Patients With Metastatic HRPC |
| NCT00672581 | PHASE1 | COMPLETED | Pharmacokinetics, Safety & Tolerability of ZD4054 (Zibotentan) in Subjects With Normal, Mild, Moderate and Severe Hepatic Impairment |
| NCT00709553 | PHASE1 | COMPLETED | Drug Interaction Study to Asses Multiple Doses of ZD4054 (Zibotentan) |
| NCT00710047 | PHASE1 | COMPLETED | Food Effect Study of a Single Dose of ZD4054 (Zibotentan) |
| NCT00713336 | PHASE1 | COMPLETED | Four-period Crossover Study to Assess the Effects of Single Oral Doses of ZD4054 (Zibotentan) (10mg and 30mg) on QTc Interval |
| NCT00713791 | PHASE1 | COMPLETED | Relative Bioavailability Study in Healthy Male Subjects for ZD4054 (Zibotentan) Immediate Release Tablets. |
| NCT00997945 | PHASE1 | COMPLETED | 10mg ZD4054 (Zibotentan) PK Study in Male, Elderly Chinese Patients With Advanced Solid Malignancies |
| NCT04991571 | PHASE1 | COMPLETED | Study to Collect Samples for MIST Analysis of Zibotentan and Bioavailability of Zibotentan and Dapagliflozin in Heatlhy Participants |
| NCT05112419 | PHASE1 | COMPLETED | A Study to Assess Zibotentan Pharmacokinetics in Participants With Moderate Hepatic and Moderate Renal Impairment |
| NCT05505162 | PHASE1 | COMPLETED | Assessing the Effect of Multiple Doses of Zibotentan on the Pharmacokinetics of Single Doses of Combined Oral Contraceptives in Healthy Female Participants of Non-childbearing Potential. |
| NCT06715670 | PHASE1 | COMPLETED | A Study to Investigate the Blood Concentrations of 4 Different Oral Doses of Zibotentan in Healthy Non-Asian and Japanese Participants |
| NCT07404137 | PHASE1 | COMPLETED | A Study to Investigate the Concentrations of Zibotentan and Dapagliflozin in Blood When Given With and Without Food |
| NCT01168141 | Not specified | UNKNOWN | Window Study of ZD4054 in Metastatic Prostate Cancer |
Clinical evidence (CIViC)
No CIViC predictive evidence (expected for non-precision-medicine drugs).
Pharmacology
Pharmacogenomics
No PharmGKB pharmacogenomic data curated for this drug.
Related molecules
Related molecules
Molecules sharing ≥1 of this drug’s curated primary targets, merged from two biobtree sources and ranked by shared-target count, then clinical phase: ChEMBL clinical-stage candidates (development phase ≥2) and PubChem drug-class bioactivity (approved / known drugs acting on the target). Deduplicated by drug name; the drug’s own salt forms are excluded. Note: for a drug with few primary targets a shared-target match can reflect off-target / promiscuous binding rather than the same therapeutic mechanism — the phase ordering surfaces bona-fide therapeutics first.
41 molecules share ≥1 primary target. Top 41 by shared-target count:
| Molecule | Source | Status | Shared targets |
|---|---|---|---|
| BOSENTAN | ChEMBL + PubChem | Phase 4 (approved) | EDNRA |
| SPARSENTAN | ChEMBL + PubChem | Phase 4 (approved) | EDNRA |
| ACYCLOVIR | ChEMBL | Phase 4 (approved) | EDNRA |
| AMBRISENTAN | ChEMBL | Phase 4 (approved) | EDNRA |
| AMIODARONE | ChEMBL | Phase 4 (approved) | EDNRA |
| APROCITENTAN | ChEMBL | Phase 4 (approved) | EDNRA |
| ENOXACIN | ChEMBL | Phase 4 (approved) | EDNRA |
| FLUOXETINE | ChEMBL | Phase 4 (approved) | EDNRA |
| GRAMICIDIN | ChEMBL | Phase 4 (approved) | EDNRA |
| IRBESARTAN | ChEMBL | Phase 4 (approved) | EDNRA |
| MACITENTAN | ChEMBL | Phase 4 (approved) | EDNRA |
| MELOXICAM | ChEMBL | Phase 4 (approved) | EDNRA |
| NITAZOXANIDE | ChEMBL | Phase 4 (approved) | EDNRA |
| PIOGLITAZONE | ChEMBL | Phase 4 (approved) | EDNRA |
| SITAXENTAN | ChEMBL | Phase 4 (approved) | EDNRA |
| SULFATHIAZOLE | ChEMBL | Phase 4 (approved) | EDNRA |
| SULFISOXAZOLE | ChEMBL | Phase 4 (approved) | EDNRA |
| SUNITINIB | ChEMBL | Phase 4 (approved) | EDNRA |
| ATRASENTAN | ChEMBL | Phase 3 | EDNRA |
| AVOSENTAN | ChEMBL | Phase 3 | EDNRA |
| CLAZOSENTAN | ChEMBL | Phase 3 | EDNRA |
| DARUSENTAN | ChEMBL | Phase 3 | EDNRA |
| EXISULIND | ChEMBL | Phase 3 | EDNRA |
| TEZOSENTAN | ChEMBL | Phase 3 | EDNRA |
| BQ-123 | ChEMBL | Phase 2 | EDNRA |
| EDONENTAN | ChEMBL | Phase 2 | EDNRA |
| ENDOTHELIN | ChEMBL | Phase 2 | EDNRA |
| ENRASENTAN | ChEMBL | Phase 2 | EDNRA |
| FANDOSENTAN | ChEMBL | Phase 2 | EDNRA |
| FELOPRENTAN | ChEMBL | Phase 2 | EDNRA |
| Afatinib | PubChem | Approved | EDNRA |
| Apixaban | PubChem | Approved | EDNRA |
| Binimetinib | PubChem | Approved | EDNRA |
| chenodiol | PubChem | Approved | EDNRA |
| Dihydroergotamine | PubChem | Approved | EDNRA |
| Fidaxomicin | PubChem | Approved | EDNRA |
| Fulvestrant | PubChem | Approved | EDNRA |
| Imipenem | PubChem | Approved | EDNRA |
| Propoxyphene | PubChem | Approved | EDNRA |
| Pyrazinamide | PubChem | Approved | EDNRA |
| Tafamidis | PubChem | Approved | EDNRA |
Related Atlas pages
- Genes: EDNRA
- Drugs: Bosentan, Sparsentan, Acyclovir, Ambrisentan, Amiodarone, Aprocitentan, Enoxacin, Fluoxetine, Gramicidin, Irbesartan, Macitentan, Meloxicam, Nitazoxanide, Pioglitazone, Sitaxentan, Sulfathiazole, Sulfisoxazole, Sunitinib, Atrasentan, Avosentan, Clazosentan, Darusentan, Exisulind, Tezosentan, Afatinib, Apixaban, Binimetinib, chenodiol, Dihydroergotamine, Fidaxomicin, Fulvestrant, Imipenem, Propoxyphene, Pyrazinamide, Tafamidis