Orteronel
drugOn this page
Also known as TAK-700(S)-Orteronel
Summary
Orteronel (CHEMBL1921976) is a phase-3 clinical-stage small-molecule antineoplastic agent targeting CYP17A1; indicated across 4 conditions including prostate adenocarcinoma and neoplasm.
At a glance
- Status: Max clinical phase 3 (not approved)
- Modality: Small molecule
- Targets: 1 (CYP17A1)
- Indications: 4 conditions
- Clinical trials: 17
- Chemistry: 307.3 Da · C18H17N3O2
Identifiers
Drug identity and classification
| Field | Value |
|---|---|
| ChEMBL ID | CHEMBL1921976 |
| Name | Orteronel |
| Type | Small molecule |
| Max phase | 3 |
| FDA approved | no |
| PubChem CID | 9796590 |
| ChEBI | CHEBI:231353 |
| Molecular formula | C18H17N3O2 |
| Molecular weight | 307.3 |
| InChIKey | OZPFIJIOIVJZMN-SFHVURJKSA-N |
SMILES: CNC(=O)C1=CC2=C(C=C1)C=C(C=C2)[C@]3(CCN4C3=CN=C4)O
IUPAC name: 6-[(7S)-7-hydroxy-5,6-dihydropyrrolo[1,2-c]imidazol-7-yl]-N-methylnaphthalene-2-carboxamide
ChEBI definition: A member of the class of pyrroloimidazoles that is 6,7-dihydro-5H-pyrrolo[1,2-c]imidazole substituted by hydroxy and 6-(methylcarbamoyl)naphthalen-2-yl groups at position 7 (the 7S-stereoisomer). It is a non-steroidal 17,20-lyase inhibitor that suppresses androgen synthesis. It was previously in clinical development for the treatment of castration-resistant prostate cancer — trial now discontinued.
Pharmacological roles (ChEBI): antineoplastic agent, sterol biosynthesis inhibitor, EC 1.14.99.9 (steroid 17α-monooxygenase) inhibitor.
Also known as: Orteronel, TAK-700, ORTERONEL, (S)-Orteronel
Patent coverage: 252 distinct patent families (602 SureChEMBL compound mentions), from 2 matched compound structure(s). One matched structure accounts for 559 (93%) 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 |
|---|---|---|---|---|---|
| CYP17A1 | CYP17A1 | Inhibition | 7.72 | 0.1% | P05093 |
Broader ChEMBL bioactivity targets: 5 (assay-derived). Sample: Steroid 21-hydroxylase, Cytochrome P450 1A2, Steroid 17-alpha-hydroxylase/17,20 lyase, Cytochrome P450 2C19, Steroid 17-alpha-hydroxylase/17,20 lyase.
Bioactivity
ChEMBL activities: 8 potent at pChembl ≥ 5 of 10 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):
| Target | pChembl | Type | Value | Unit | Activity ID |
|---|---|---|---|---|---|
| CYP17A1 | 8.4 | IC50 | 4 | nM | CHEMBL_ACT_27120020 |
| CYP21A2 | 8.4 | IC50 | 4 | nM | CHEMBL_ACT_27120062 |
| CYP17A1 | 7.72 | IC50 | 19 | nM | CHEMBL_ACT_7947800 |
| CYP17A1 | 7.4 | Kd | 40 | nM | CHEMBL_ACT_20607521 |
| P11715 | 7.32 | IC50 | 48 | nM | CHEMBL_ACT_7947798 |
| CYP17A1 | 6.57 | IC50 | 270 | nM | CHEMBL_ACT_20607522 |
| CYP17A1 | 5.33 | IC50 | 4730 | nM | CHEMBL_ACT_18710926 |
| CYP21A2 | 5.31 | IC50 | 4870 | nM | CHEMBL_ACT_18710950 |
Target pathways
Aggregated over 1 target gene(s): CYP17A1.
Top Reactome pathways
3 total, by targets touching each:
| Pathway | Targets | Genes |
|---|---|---|
| Androgen biosynthesis | 1 | CYP17A1 |
| Glucocorticoid biosynthesis | 1 | CYP17A1 |
| Defective CYP17A1 causes AH5 | 1 | CYP17A1 |
Dominant GO biological processes
| GO term | Targets |
|---|---|
| steroid biosynthetic process | 1 |
| androgen biosynthetic process | 1 |
| glucocorticoid biosynthetic process | 1 |
| sex differentiation | 1 |
| steroid metabolic process | 1 |
| cortisol biosynthetic process | 1 |
| hormone biosynthetic process | 1 |
| progesterone metabolic process | 1 |
| lipid metabolic process | 1 |
| hormone metabolic process | 1 |
| olefinic compound metabolic process | 1 |
Indications & clinical
Indications
4 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 |
| neoplasm | 2 | MONDO:0005070 | EFO:0000616 |
| breast neoplasm | 2 | MONDO:0021100 | MONDO:0007254 |
1 further indication record had no mapped disease name (EFO/MeSH-only) or were duplicates, and are omitted.
Clinical trials
Total trials: 17.
Phase distribution
| Phase | Trials |
|---|---|
| PHASE2 | 7 |
| PHASE3 | 6 |
| PHASE1/PHASE2 | 4 |
Top trials by phase / activity
| NCT | Phase | Status | Title |
|---|---|---|---|
| NCT01193244 | PHASE3 | COMPLETED | Study Comparing Orteronel Plus Prednisone in Participants With Chemotherapy-Naive Metastatic Castration-Resistant Prostate Cancer |
| NCT01193257 | PHASE3 | COMPLETED | Study Comparing Orteronel Plus Prednisone in Participants With Metastatic Castration-Resistant Prostate Cancer. |
| NCT01546987 | PHASE3 | COMPLETED | Hormone Therapy, Radiation Therapy, and Steroid 17alpha-monooxygenase TAK-700 in Treating Patients With High-Risk Prostate Cancer |
| NCT01707966 | PHASE3 | COMPLETED | Orteronel Maintenance Therapy in Patients With Metastatic Castration Resistant Prostate Cancer and Non-progressive Disease After First-line Docetaxel Therapy |
| NCT01809691 | PHASE3 | COMPLETED | S1216, Phase III ADT+TAK-700 vs. ADT+Bicalutamide for Metastatic Prostate Cancer |
| NCT02053311 | PHASE3 | WITHDRAWN | Orteronel Maintenance Therapy in Patients With mCRPC Previously Treated With Novel Hormonal Agents |
| NCT00569153 | PHASE1/PHASE2 | COMPLETED | Safety Study of TAK-700 in Subjects With Prostate Cancer. |
| NCT01046916 | PHASE2 | COMPLETED | Safety and Efficacy Study of TAK-700 in Patients With Nonmetastatic Castration-resistant Prostate Cancer and a Rising Prostate-specific Antigen |
| NCT01084655 | PHASE1/PHASE2 | COMPLETED | Study of TAK-700 in Combination With Docetaxel and Prednisone in Men With Metastatic Castration-Resistant Prostate Cancer |
| NCT01549951 | PHASE2 | COMPLETED | Study to Investigate the Effects of Orteronel on the QT/QTc Interval in Patients With Metastatic Castration-Resistant Prostate Cancer |
| NCT01658527 | PHASE2 | WITHDRAWN | TAK-700 in Castration Resistant Prostate Cancer |
| NCT01666314 | PHASE1/PHASE2 | COMPLETED | Study in Japan and Ex-Japan to Characterize the Pharmacokinetic and Pharmacodynamic Response to Orteronel (TAK-700) in Chemotherapy-Naive Participants With Castration-Resistant Prostate Cancer |
| NCT01816048 | PHASE2 | TERMINATED | NaF Positron Emission Tomography/Computed Tomography (PET/CT)Imaging to Assess Treatment Responsiveness to TAK-700 in Patients With Castrate Resistant Prostate Cancer (CRPC) With Bone Metastasis |
| NCT01866423 | PHASE2 | TERMINATED | Orteronel in Treating Patients With Metastatic Hormone-Resistant Prostate Cancer |
| NCT01990209 | PHASE2 | COMPLETED | Orteronel as Monotherapy in Patients With Metastatic Breast Cancer (MBC) That Expresses the Androgen Receptor (AR) |
| NCT02054793 | PHASE1/PHASE2 | WITHDRAWN | Phase Ib/II Study Evaluating Orteronel (Without Prednisone) Combined With Itraconazole In Men With Castration-Resistant Prostate Cancer (CRPC) |
| NCT03211052 | PHASE2 | TERMINATED | A Study of Neoadjuvant TAK-700 and Leuprorelin Acetate Followed by Surgery Versus Surgery Alone |
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.
20 molecules share ≥1 primary target. Top 20 by shared-target count:
| Molecule | Source | Status | Shared targets |
|---|---|---|---|
| ABIRATERONE | ChEMBL + PubChem | Phase 4 (approved) | CYP17A1 |
| CLOTRIMAZOLE | ChEMBL + PubChem | Phase 4 (approved) | CYP17A1 |
| ECONAZOLE | ChEMBL + PubChem | Phase 4 (approved) | CYP17A1 |
| MICONAZOLE | ChEMBL + PubChem | Phase 4 (approved) | CYP17A1 |
| OSILODROSTAT | ChEMBL + PubChem | Phase 4 (approved) | CYP17A1 |
| AMINOGLUTETHIMIDE | ChEMBL | Phase 4 (approved) | CYP17A1 |
| BIFONAZOLE | ChEMBL | Phase 4 (approved) | CYP17A1 |
| ISOCONAZOLE | ChEMBL | Phase 4 (approved) | CYP17A1 |
| KETOCONAZOLE | ChEMBL | Phase 4 (approved) | CYP17A1 |
| POSACONAZOLE | ChEMBL | Phase 4 (approved) | CYP17A1 |
| TESTOSTERONE PROPIONATE | ChEMBL | Phase 4 (approved) | CYP17A1 |
| TIOCONAZOLE | ChEMBL | Phase 4 (approved) | CYP17A1 |
| GALETERONE | ChEMBL | Phase 3 | CYP17A1 |
| AZALANSTAT | ChEMBL | Phase 2 | CYP17A1 |
| Bicalutamide | PubChem | Approved | CYP17A1 |
| Enzalutamide | PubChem | Approved | CYP17A1 |
| Fluconazole | PubChem | Approved | CYP17A1 |
| Flutamide | PubChem | Approved | CYP17A1 |
| Letrozole | PubChem | Approved | CYP17A1 |
| Metyrapone | PubChem | Approved | CYP17A1 |