Voxelotor
drugOn this page
Also known as GBT-440Gbt440GTX-011Oxbryta
Summary
Voxelotor (CHEMBL4101807) is an approved small molecule (ATC B06AX03) targeting CYP2C8, CYP2C9, and CYP3A4; indicated across 7 conditions including sickle cell disease and anemia.
At a glance
- Status: Approved (max clinical phase 4)
- Modality: Small molecule
- ATC class: B06AX03
- Targets: 3 (CYP2C8, CYP2C9, CYP3A4)
- Indications: 7 conditions
- Clinical trials: 27
- Chemistry: 337.4 Da · C19H19N3O3
Identifiers
Drug identity and classification
| Field | Value |
|---|---|
| ChEMBL ID | CHEMBL4101807 |
| Name | Voxelotor |
| Type | Small molecule |
| Max phase | 4 |
| FDA approved | yes |
| PubChem CID | 71602803 |
| ATC | B06AX03 |
| Molecular formula | C19H19N3O3 |
| Molecular weight | 337.4 |
| InChIKey | FWCVZAQENIZVMY-UHFFFAOYSA-N |
SMILES: CC(C)N1C(=CC=N1)C2=C(C=CC=N2)COC3=CC=CC(=C3C=O)O
IUPAC name: 2-hydroxy-6-[[2-(2-propan-2-ylpyrazol-3-yl)-3-pyridinyl]methoxy]benzaldehyde
Also known as: GBT-440, Gbt440, GBT440, GTX-011, Oxbryta, Voxelotor, VOXELOTOR
Patent coverage: 163 distinct patent families (433 SureChEMBL compound mentions), from 1 matched compound structure(s). 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 |
|---|---|---|---|---|---|
| CYP2C8 | CYP2C8 | Inhibition | 5.1 | 0.2% | P10632 |
| CYP2C9 | CYP2C9 | Inhibition | 5.07 | 0% | P11712 |
| CYP3A4 | CYP3A4 | Inhibition | 4.9 | 0% | P08684 |
Broader ChEMBL bioactivity targets: 5 (assay-derived). Sample: Cytochrome P450 1A2, Cytochrome P450 2C9, Cytochrome P450 3A4, Cytochrome P450 2C19, Cytochrome P450 2C8.
Bioactivity
ChEMBL activities: 2 potent at pChembl ≥ 5 of 6 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):
| Target | pChembl | Type | Value | Unit | Activity ID |
|---|---|---|---|---|---|
| CYP2C8 | 5.1 | IC50 | 7900 | nM | CHEMBL_ACT_18015161 |
| CYP2C9 | 5.07 | IC50 | 8500 | nM | CHEMBL_ACT_18015162 |
Target pathways
Aggregated over 3 target gene(s): CYP2C8, CYP2C9, CYP3A4.
Top Reactome pathways
10 total, by targets touching each:
| Pathway | Targets | Genes |
|---|---|---|
| Xenobiotics | 3 | CYP2C8, CYP2C9, CYP3A4 |
| Biosynthesis of maresin-like SPMs | 3 | CYP2C8, CYP2C9, CYP3A4 |
| Aspirin ADME | 3 | CYP2C8, CYP2C9, CYP3A4 |
| CYP2E1 reactions | 2 | CYP2C8, CYP2C9 |
| Synthesis of epoxy (EET) and dihydroxyeicosatrienoic acids (DHET) | 2 | CYP2C8, CYP2C9 |
| Synthesis of (16-20)-hydroxyeicosatetraenoic acids (HETE) | 2 | CYP2C8, CYP2C9 |
| Phase I - Functionalization of compounds | 1 | CYP3A4 |
| Aflatoxin activation and detoxification | 1 | CYP3A4 |
| Atorvastatin ADME | 1 | CYP3A4 |
| Prednisone ADME | 1 | CYP3A4 |
Dominant GO biological processes
| GO term | Targets |
|---|---|
| xenobiotic metabolic process | 3 |
| steroid metabolic process | 3 |
| estrogen metabolic process | 3 |
| xenobiotic catabolic process | 3 |
| long-chain fatty acid biosynthetic process | 3 |
| oxidative demethylation | 3 |
| lipid metabolic process | 3 |
| lipid hydroxylation | 2 |
| epoxygenase P450 pathway | 2 |
| retinol metabolic process | 2 |
| retinoic acid metabolic process | 2 |
| icosanoid biosynthetic process | 2 |
| omega-hydroxylase P450 pathway | 2 |
| terpenoid metabolic process | 2 |
| arachidonate metabolic process | 2 |
Indications & clinical
Indications
7 indications (3 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 |
|---|---|---|---|
| sickle cell disease | 4 | MONDO:0011382 | MONDO:0011382 |
| anemia | 4 | MONDO:0002280 | EFO:0004272 |
| hemolytic anemia | 4 | MONDO:0003664 | MONDO:0002280 |
| idiopathic pulmonary fibrosis | 2 | MONDO:0800504 | EFO:0000768 |
| acute lung injury | 2 | MONDO:0015796 | EFO:0004610 |
| liver disorder | 1 | MONDO:0005154 | EFO:0001421 |
| kidney disorder | 1 | MONDO:0005240 | EFO:0003086 |
Clinical trials
Total trials: 27.
Phase distribution
| Phase | Trials |
|---|---|
| PHASE2 | 8 |
| PHASE1 | 8 |
| PHASE3 | 5 |
| PHASE4 | 3 |
| Not specified | 2 |
| PHASE1/PHASE2 | 1 |
Top trials by phase / activity
| NCT | Phase | Status | Title |
|---|---|---|---|
| NCT04400487 | PHASE4 | COMPLETED | Actigraphy Improvement With Voxelotor (ActIVe) Study |
| NCT04581356 | PHASE4 | COMPLETED | Voxelotor Sickle Cell Exercise Study |
| NCT05228821 | PHASE4 | WITHDRAWN | Voxelotor Brain Oxygenation and Neurocognitive Study |
| NCT03036813 | PHASE3 | COMPLETED | Study to Evaluate the Effect of Voxelotor Administered Orally to Patients With Sickle Cell Disease (GBT_HOPE) |
| NCT03573882 | PHASE3 | TERMINATED | Study to Assess the Effect of Long-term Treatment With Voxelotor in Participants Who Have Completed Treatment in Study GBT440-031 |
| NCT04188509 | PHASE3 | TERMINATED | Open-Label Extension of Voxelotor |
| NCT04218084 | PHASE3 | TERMINATED | Study to Evaluate the Effect of GBT440 on TCD in Pediatrics With Sickle Cell Disease |
| NCT05561140 | PHASE3 | TERMINATED | Resolution of Sickle Cell Leg Ulcers With Voxelotor |
| NCT06023199 | PHASE2 | ACTIVE_NOT_RECRUITING | Assessing Physical Function in Sickle Cell Patients Taking Voxelotor |
| NCT02846324 | PHASE2 | COMPLETED | Study to Evaluate the Safety and Tolerability of GBT440 Administered to Subjects With IPF |
| NCT02850406 | PHASE2 | TERMINATED | Study to Evaluate the Effect of GBT440 in Pediatrics With Sickle Cell Disease |
| NCT02989168 | PHASE2 | TERMINATED | Study to Evaluate the Effect of GBT440 Administered to Subjects With IPF on Supplemental Oxygen at Rest |
| NCT03041909 | PHASE2 | COMPLETED | An Extension Study to Further Evaluate the Safety, Tolerability of GBT440 in Patients With Sickle Cell Disease Who Participated in the Study GBT440-001 |
| NCT04247594 | PHASE2 | TERMINATED | Dose Escalation Study to Evaluate the Safety, Tolerability, PK and PD of Voxelotor in Patients With SCD |
| NCT04335721 | PHASE1/PHASE2 | TERMINATED | A Voxelotor for Sickle Cell Anemia Patients at Highest Risk for Progression of Chronic Kidney Disease |
| NCT05018728 | PHASE2 | TERMINATED | The Effect of Voxelotor on Cerebral Hemodynamic Response in Children With Sickle Cell Anemia |
| NCT05289570 | PHASE2 | TERMINATED | Voxelotor for Improving Oxygen Saturation in Adults |
| NCT02285088 | PHASE1 | COMPLETED | A Study of the Safety, Blood Levels and Biological Effects of GBT440 in Healthy Subjects and Subjects With Sickle Cell Disease |
| NCT02497924 | PHASE1 | COMPLETED | A Study of the Absorption, Metabolism, and Excretion of GBT440 in Healthy Male Subjects |
| NCT02567682 | PHASE1 | COMPLETED | Drug Interaction Study of GBT440 With Caffeine, S-warfarin, Omeprazole, and Midazolam in Healthy Subjects |
| NCT02567695 | PHASE1 | COMPLETED | A Single-Dose Relative Bioavailability Study Of GBT440 300 mg Capsules in Healthy Subjects |
| NCT03051711 | PHASE1 | TERMINATED | Study to Evaluate Effects of Investigational Drug on Oxygenation in Healthy Volunteers Under Hypoxic Conditions |
| NCT03114540 | PHASE1 | COMPLETED | Single-Dose PK and Safety Study of GBT440 in Subjects With Hepatic Impairment |
| NCT03161015 | PHASE1 | COMPLETED | Single-Dose PK Study of GBT440 in Subjects With Renal Impairment |
| NCT05981365 | PHASE1 | COMPLETED | Voxelotor CYP and Transporter Cocktail Interaction Study |
| NCT03943615 | Not specified | NO_LONGER_AVAILABLE | Expanded Access to Voxelotor for Patients With Sickle Cell Disease Who Have No Alternative Treatment Options |
| NCT04724421 | Not specified | NO_LONGER_AVAILABLE | Expanded Access Protocol for Adults and Pediatric Patients With Sickle Cell Disease Who Have No Alternative Treatment Options |
Clinical evidence (CIViC)
No CIViC predictive evidence (expected for non-precision-medicine drugs).
Pharmacology
Pharmacogenomics
No CPIC/DPWG dosing guideline or drug-level clinical/variant annotations in PharmGKB for this molecule.
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.
738 molecules share ≥1 primary target. Top 60 by shared-target count:
| Molecule | Source | Status | Shared targets |
|---|---|---|---|
| Carfilzomib | ChEMBL + PubChem | Phase 4 (approved) | CYP2C8, CYP2C9, CYP3A4 |
| Clozapine | ChEMBL + PubChem | Phase 4 (approved) | CYP2C8, CYP2C9, CYP3A4 |
| PAZOPANIB | ChEMBL + PubChem | Phase 4 (approved) | CYP2C8, CYP2C9, CYP3A4 |
| saxagliptin | ChEMBL + PubChem | Phase 4 (approved) | CYP2C8, CYP2C9, CYP3A4 |
| ZANUBRUTINIB | ChEMBL + PubChem | Phase 4 (approved) | CYP2C8, CYP2C9, CYP3A4 |
| AMIODARONE | ChEMBL | Phase 4 (approved) | CYP2C8, CYP2C9, CYP3A4 |
| CLOTRIMAZOLE | ChEMBL | Phase 4 (approved) | CYP2C8, CYP2C9, CYP3A4 |
| IBRUTINIB | ChEMBL | Phase 4 (approved) | CYP2C8, CYP2C9, CYP3A4 |
| ISRADIPINE | ChEMBL | Phase 4 (approved) | CYP2C8, CYP2C9, CYP3A4 |
| KETOCONAZOLE | ChEMBL | Phase 4 (approved) | CYP2C8, CYP2C9, CYP3A4 |
| LANSOPRAZOLE | ChEMBL | Phase 4 (approved) | CYP2C8, CYP2C9, CYP3A4 |
| MIFEPRISTONE | ChEMBL | Phase 4 (approved) | CYP2C8, CYP2C9, CYP3A4 |
| NICARDIPINE | ChEMBL | Phase 4 (approved) | CYP2C8, CYP2C9, CYP3A4 |
| PHENELZINE | ChEMBL | Phase 4 (approved) | CYP2C8, CYP2C9, CYP3A4 |
| QUERCETIN | ChEMBL | Phase 3 | CYP2C8, CYP2C9, CYP3A4 |
| RELACORILANT | ChEMBL | Phase 3 | CYP2C8, CYP2C9, CYP3A4 |
| SERLOPITANT | ChEMBL | Phase 3 | CYP2C8, CYP2C9, CYP3A4 |
| SOTICLESTAT | ChEMBL | Phase 3 | CYP2C8, CYP2C9, CYP3A4 |
| TEMSAVIR | ChEMBL + PubChem | Phase 2 (approved) | CYP2C8, CYP2C9, CYP3A4 |
| APINOCALTAMIDE | ChEMBL | Phase 2 | CYP2C8, CYP2C9, CYP3A4 |
| BMS-986142 | ChEMBL | Phase 2 | CYP2C8, CYP2C9, CYP3A4 |
| LIAROZOLE | ChEMBL | Phase 2 | CYP2C8, CYP2C9, CYP3A4 |
| MK-0893 | ChEMBL | Phase 2 | CYP2C8, CYP2C9, CYP3A4 |
| TALAROZOLE | ChEMBL | Phase 2 | CYP2C8, CYP2C9, CYP3A4 |
| UDIFITIMOD | ChEMBL | Phase 2 | CYP2C8, CYP2C9, CYP3A4 |
| Aprepitant | ChEMBL + PubChem | Phase 4 (approved) | CYP2C8, CYP3A4 |
| Erythromycin | ChEMBL + PubChem | Phase 4 (approved) | CYP2C8, CYP3A4 |
| FEZOLINETANT | ChEMBL + PubChem | Phase 4 (approved) | CYP2C9, CYP3A4 |
| AMSACRINE | ChEMBL | Phase 4 (approved) | CYP2C9, CYP3A4 |
| APOMORPHINE | ChEMBL | Phase 4 (approved) | CYP2C9, CYP3A4 |
| BENZBROMARONE | ChEMBL | Phase 4 (approved) | CYP2C9, CYP3A4 |
| BENZTHIAZIDE | ChEMBL | Phase 4 (approved) | CYP2C9, CYP3A4 |
| BEPRIDIL | ChEMBL | Phase 4 (approved) | CYP2C9, CYP3A4 |
| BUSPIRONE | ChEMBL | Phase 4 (approved) | CYP2C9, CYP3A4 |
| BUTAMBEN | ChEMBL | Phase 4 (approved) | CYP2C9, CYP3A4 |
| CANNABIDIOL | ChEMBL | Phase 4 (approved) | CYP2C9, CYP3A4 |
| CELECOXIB | ChEMBL | Phase 4 (approved) | CYP2C9, CYP3A4 |
| CLEMASTINE | ChEMBL | Phase 4 (approved) | CYP2C9, CYP3A4 |
| COLCHICINE | ChEMBL | Phase 4 (approved) | CYP2C9, CYP3A4 |
| CYCLOSPORINE | ChEMBL | Phase 4 (approved) | CYP2C9, CYP3A4 |
| DACLATASVIR | ChEMBL | Phase 4 (approved) | CYP2C9, CYP3A4 |
| DANAZOL | ChEMBL | Phase 4 (approved) | CYP2C8, CYP2C9 |
| DAPSONE | ChEMBL | Phase 4 (approved) | CYP2C9, CYP3A4 |
| DASATINIB | ChEMBL | Phase 4 (approved) | CYP2C9, CYP3A4 |
| DICLOFENAC | ChEMBL | Phase 4 (approved) | CYP2C9, CYP3A4 |
| DICUMAROL | ChEMBL | Phase 4 (approved) | CYP2C9, CYP3A4 |
| DICYCLOMINE | ChEMBL | Phase 4 (approved) | CYP2C9, CYP3A4 |
| DIENESTROL | ChEMBL | Phase 4 (approved) | CYP2C9, CYP3A4 |
| DIETHYLSTILBESTROL | ChEMBL | Phase 4 (approved) | CYP2C9, CYP3A4 |
| DROPERIDOL | ChEMBL | Phase 4 (approved) | CYP2C9, CYP3A4 |
| DULOXETINE | ChEMBL | Phase 4 (approved) | CYP2C9, CYP3A4 |
| DYCLONINE | ChEMBL | Phase 4 (approved) | CYP2C9, CYP3A4 |
| ENOXIMONE | ChEMBL | Phase 4 (approved) | CYP2C9, CYP3A4 |
| ESCITALOPRAM | ChEMBL | Phase 4 (approved) | CYP2C9, CYP3A4 |
| ETODOLAC | ChEMBL | Phase 4 (approved) | CYP2C9, CYP3A4 |
| ETRAVIRINE | ChEMBL | Phase 4 (approved) | CYP2C9, CYP3A4 |
| FENOFIBRATE | ChEMBL | Phase 4 (approved) | CYP2C9, CYP3A4 |
| FINASTERIDE | ChEMBL | Phase 4 (approved) | CYP2C9, CYP3A4 |
| FLUCONAZOLE | ChEMBL | Phase 4 (approved) | CYP2C9, CYP3A4 |
| FLUPIRTINE | ChEMBL | Phase 4 (approved) | CYP2C9, CYP3A4 |
Related Atlas pages
- Genes: CYP2C8, CYP2C9, CYP3A4
- Diseases: sickle cell disease, anemia, hemolytic anemia
- Drugs: Carfilzomib, Clozapine, Pazopanib, saxagliptin, Zanubrutinib, Amiodarone, Clotrimazole, Ibrutinib, Isradipine, Ketoconazole, Lansoprazole, Mifepristone, Nicardipine, Phenelzine, Quercetin, Relacorilant, Serlopitant, Soticlestat, Aprepitant, Erythromycin, Fezolinetant, Amsacrine, Apomorphine, Benzbromarone, Benzthiazide, Bepridil, Buspirone, Butamben, Cannabidiol, Celecoxib, Clemastine, Colchicine, Cyclosporine, Daclatasvir, Danazol, Dapsone, Dasatinib, Diclofenac, Dicumarol, Dicyclomine, Dienestrol, Diethylstilbestrol, Droperidol, Duloxetine, Dyclonine, Enoximone, Escitalopram, Etodolac, Etravirine, Fenofibrate, Finasteride, Fluconazole, Flupirtine