Naquotinib
drugOn this page
Also known as ASP-8273ASP8273US9085540, 54
Summary
Naquotinib (CHEMBL3663929) is a phase-3 clinical-stage small molecule targeting EGFR; indicated across 2 conditions including non-small cell lung carcinoma and neoplasm; with CIViC clinical evidence for 1 variant-indication association (e.g. EGFR T790M in lung non-small cell carcinoma).
At a glance
- Status: Max clinical phase 3 (not approved)
- Modality: Small molecule
- Targets: 1 (EGFR)
- Indications: 2 conditions
- Clinical trials: 6
- Precision-oncology evidence (CIViC): 1 variant–indication association
- Chemistry: 562.7 Da · C30H42N8O3
Identifiers
Drug identity and classification
| Field | Value |
|---|---|
| ChEMBL ID | CHEMBL3663929 |
| Name | Naquotinib |
| Type | Small molecule |
| Max phase | 3 |
| FDA approved | no |
| PubChem CID | 71667668 |
| Molecular formula | C30H42N8O3 |
| Molecular weight | 562.7 |
| InChIKey | QKDCLUARMDUUKN-XMMPIXPASA-N |
SMILES: CCC1=C(N=C(C(=N1)C(=O)N)NC2=CC=C(C=C2)N3CCC(CC3)N4CCN(CC4)C)O[C@@H]5CCN(C5)C(=O)C=C
IUPAC name: 6-ethyl-3-[4-[4-(4-methylpiperazin-1-yl)piperidin-1-yl]anilino]-5-[(3R)-1-prop-2-enoylpyrrolidin-3-yl]oxypyrazine-2-carboxamide
Also known as: ASP-8273, ASP8273, Naquotinib, US9085540, 54, NAQUOTINIB
Parent form; salt/anhydrous children: CHEMBL3707350
Patent coverage: 358 distinct patent families (843 SureChEMBL compound mentions), from 2 matched compound structure(s). One matched structure accounts for 806 (96%) 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 |
|---|---|---|---|---|---|
| EGFR | epidermal growth factor receptor | Inhibition | 17.5% | P00533 |
Broader ChEMBL bioactivity targets: 1 (assay-derived). Sample: Epidermal growth factor receptor.
Bioactivity
ChEMBL activities: 7 potent at pChembl ≥ 5 of 7 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):
| Target | pChembl | Type | Value | Unit | Activity ID |
|---|---|---|---|---|---|
| EGFR | 8.77 | IC50 | 1.7 | nM | CHEMBL_ACT_17694626 |
| EGFR | 8.35 | IC50 | 4.5 | nM | CHEMBL_ACT_17694643 |
| EGFR | 8.1 | IC50 | 8 | nM | CHEMBL_ACT_16532771 |
| EGFR | 8.1 | IC50 | 8 | nM | CHEMBL_ACT_16532772 |
| EGFR | 8.1 | IC50 | 8 | nM | CHEMBL_ACT_16532773 |
| EGFR | 8.1 | IC50 | 8 | nM | CHEMBL_ACT_16532774 |
| EGFR | 6.64 | IC50 | 230 | nM | CHEMBL_ACT_16532775 |
Target pathways
Aggregated over 1 target gene(s): EGFR.
Top Reactome pathways
37 total, by targets touching each:
| Pathway | Targets | Genes |
|---|---|---|
| Signaling by ERBB2 | 1 | EGFR |
| Constitutive Signaling by Ligand-Responsive EGFR Cancer Variants | 1 | EGFR |
| Signaling by ERBB4 | 1 | EGFR |
| SHC1 events in ERBB2 signaling | 1 | EGFR |
| PLCG1 events in ERBB2 signaling | 1 | EGFR |
| PIP3 activates AKT signaling | 1 | EGFR |
| Signaling by EGFR | 1 | EGFR |
| GRB2 events in EGFR signaling | 1 | EGFR |
| GAB1 signalosome | 1 | EGFR |
| SHC1 events in EGFR signaling | 1 | EGFR |
| EGFR downregulation | 1 | EGFR |
| GRB2 events in ERBB2 signaling | 1 | EGFR |
| PI3K events in ERBB2 signaling | 1 | EGFR |
| EGFR interacts with phospholipase C-gamma | 1 | EGFR |
| EGFR Transactivation by Gastrin | 1 | EGFR |
| Constitutive Signaling by Aberrant PI3K in Cancer | 1 | EGFR |
| Signal transduction by L1 | 1 | EGFR |
| Constitutive Signaling by EGFRvIII | 1 | EGFR |
| Inhibition of Signaling by Overexpressed EGFR | 1 | EGFR |
| RAF/MAP kinase cascade | 1 | EGFR |
| ERBB2 Regulates Cell Motility | 1 | EGFR |
| PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling | 1 | EGFR |
| ERBB2 Activates PTK6 Signaling | 1 | EGFR |
| Cargo recognition for clathrin-mediated endocytosis | 1 | EGFR |
| Clathrin-mediated endocytosis | 1 | EGFR |
| PTK6 promotes HIF1A stabilization | 1 | EGFR |
| Downregulation of ERBB2 signaling | 1 | EGFR |
| TFAP2 (AP-2) family regulates transcription of growth factors and their receptors | 1 | EGFR |
| Extra-nuclear estrogen signaling | 1 | EGFR |
| NOTCH3 Activation and Transmission of Signal to the Nucleus | 1 | EGFR |
Dominant GO biological processes
| GO term | Targets |
|---|---|
| cell morphogenesis | 1 |
| ossification | 1 |
| embryonic placenta development | 1 |
| positive regulation of protein phosphorylation | 1 |
| hair follicle development | 1 |
| ubiquitin-dependent protein catabolic process | 1 |
| signal transduction | 1 |
| cell surface receptor signaling pathway | 1 |
| epidermal growth factor receptor signaling pathway | 1 |
| salivary gland morphogenesis | 1 |
| learning or memory | 1 |
| positive regulation of cell population proliferation | 1 |
| gene expression | 1 |
| protein ubiquitination | 1 |
| cerebral cortex cell migration | 1 |
Indications & clinical
Indications
2 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 |
|---|---|---|---|
| non-small cell lung carcinoma | 2 | MONDO:0005233 | EFO:0003060 |
| neoplasm | 1 | MONDO:0005070 | EFO:0000616 |
Clinical trials
Total trials: 6.
Phase distribution
| Phase | Trials |
|---|---|
| PHASE1 | 3 |
| PHASE2 | 2 |
| PHASE1/PHASE2 | 1 |
Top trials by phase / activity
| NCT | Phase | Status | Title |
|---|---|---|---|
| NCT02192697 | PHASE1/PHASE2 | TERMINATED | An Open Study of ASP8273 in Patients With Non-Small-Cell Lung Cancer (NSCLC) Who Have Epidermal Growth Factor Receptor (EGFR) Mutations |
| NCT02500927 | PHASE2 | TERMINATED | A Study of ASP8273 in Epidermal Growth Factor Receptor (EGFR) Tyrosine Kinase Inhibitor-Naïve Patients With Non-Small Cell Lung Cancer Harboring EGFR Mutations |
| NCT03042013 | PHASE2 | WITHDRAWN | A Study for Subjects Who Are Participating in an Astellas-sponsored ASP8273 Study |
| NCT02113813 | PHASE1 | COMPLETED | A Dose Escalation Study of ASP8273 in Subjects With Non-Small-Cell Lung Cancer (NSCLC) Who Have Epidermal Growth Factor Receptor (EGFR) Mutations |
| NCT02674555 | PHASE1 | WITHDRAWN | A Study to Investigate the Absorption, Metabolism and Excretion of [14C]ASP8273 in Subjects With Solid Tumors |
| NCT03082300 | PHASE1 | TERMINATED | A Study of ASP8273 in Subjects With Non-small Cell Lung Cancer (NSCLC) Harboring Epidermal Growth Factor Receptor (EGFR) Mutations |
Clinical evidence (CIViC)
Variant × indication × effect (1 predictive associations from 1 curated evidence items):
| Variant | Indication | Effect | Therapy | Level | CIViC |
|---|---|---|---|---|---|
| EGFR T790M | Lung Non-small Cell Carcinoma | Resistance | Mitogen-Activated Protein Kinase Kinase Inhibitor + Naquotinib + Osimertinib | CIViC D | EID6318 |
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.
157 molecules share ≥1 primary target. Top 60 by shared-target count:
| Molecule | Source | Status | Shared targets |
|---|---|---|---|
| AFATINIB | ChEMBL + PubChem | Phase 4 (approved) | EGFR |
| SELUMETINIB | ChEMBL + PubChem | Phase 4 (approved) | EGFR |
| ABEMACICLIB | ChEMBL | Phase 4 (approved) | EGFR |
| ACALABRUTINIB | ChEMBL | Phase 4 (approved) | EGFR |
| AFATINIB DIMALEATE | ChEMBL | Phase 4 (approved) | EGFR |
| ALECTINIB | ChEMBL | Phase 4 (approved) | EGFR |
| ASTEMIZOLE | ChEMBL | Phase 4 (approved) | EGFR |
| AXITINIB | ChEMBL | Phase 4 (approved) | EGFR |
| BACITRACIN | ChEMBL | Phase 4 (approved) | EGFR |
| BITHIONOL | ChEMBL | Phase 4 (approved) | EGFR |
| BOSUTINIB | ChEMBL | Phase 4 (approved) | EGFR |
| BRIGATINIB | ChEMBL | Phase 4 (approved) | EGFR |
| CABOZANTINIB | ChEMBL | Phase 4 (approved) | EGFR |
| CERITINIB | ChEMBL | Phase 4 (approved) | EGFR |
| CHLORPROMAZINE | ChEMBL | Phase 4 (approved) | EGFR |
| CHROMIC CHLORIDE | ChEMBL | Phase 4 (approved) | EGFR |
| CISPLATIN | ChEMBL | Phase 4 (approved) | EGFR |
| CLOTRIMAZOLE | ChEMBL | Phase 4 (approved) | EGFR |
| COLISTIN | ChEMBL | Phase 4 (approved) | EGFR |
| CRIZOTINIB | ChEMBL | Phase 4 (approved) | EGFR |
| DACOMITINIB | ChEMBL | Phase 4 (approved) | EGFR |
| DASATINIB | ChEMBL | Phase 4 (approved) | EGFR |
| DOBUTAMINE | ChEMBL | Phase 4 (approved) | EGFR |
| DOCETAXEL | ChEMBL | Phase 4 (approved) | EGFR |
| EBASTINE | ChEMBL | Phase 4 (approved) | EGFR |
| ECONAZOLE | ChEMBL | Phase 4 (approved) | EGFR |
| ERLOTINIB | ChEMBL | Phase 4 (approved) | EGFR |
| FEDRATINIB | ChEMBL | Phase 4 (approved) | EGFR |
| FLUPHENAZINE | ChEMBL | Phase 4 (approved) | EGFR |
| GEFITINIB | ChEMBL | Phase 4 (approved) | EGFR |
| GENTIAN VIOLET | ChEMBL | Phase 4 (approved) | EGFR |
| GILTERITINIB | ChEMBL | Phase 4 (approved) | EGFR |
| HEXACHLOROPHENE | ChEMBL | Phase 4 (approved) | EGFR |
| IBRUTINIB | ChEMBL | Phase 4 (approved) | EGFR |
| IMATINIB | ChEMBL | Phase 4 (approved) | EGFR |
| LAPATINIB | ChEMBL | Phase 4 (approved) | EGFR |
| LAPATINIB DITOSYLATE | ChEMBL | Phase 4 (approved) | EGFR |
| LAZERTINIB | ChEMBL | Phase 4 (approved) | EGFR |
| LEVODOPA | ChEMBL | Phase 4 (approved) | EGFR |
| LORLATINIB | ChEMBL | Phase 4 (approved) | EGFR |
| METHYLDOPA | ChEMBL | Phase 4 (approved) | EGFR |
| MICONAZOLE | ChEMBL | Phase 4 (approved) | EGFR |
| MIDOSTAURIN | ChEMBL | Phase 4 (approved) | EGFR |
| MITOXANTRONE | ChEMBL | Phase 4 (approved) | EGFR |
| MOBOCERTINIB | ChEMBL | Phase 4 (approved) | EGFR |
| MONTELUKAST | ChEMBL | Phase 4 (approved) | EGFR |
| NELFINAVIR | ChEMBL | Phase 4 (approved) | EGFR |
| NERATINIB | ChEMBL | Phase 4 (approved) | EGFR |
| NICLOSAMIDE | ChEMBL | Phase 4 (approved) | EGFR |
| OLMUTINIB | ChEMBL | Phase 4 (approved) | EGFR |
| OSIMERTINIB | ChEMBL | Phase 4 (approved) | EGFR |
| PERHEXILINE | ChEMBL | Phase 4 (approved) | EGFR |
| PONATINIB | ChEMBL | Phase 4 (approved) | EGFR |
| SORAFENIB | ChEMBL | Phase 4 (approved) | EGFR |
| SULOCTIDIL | ChEMBL | Phase 4 (approved) | EGFR |
| SUNITINIB | ChEMBL | Phase 4 (approved) | EGFR |
| TAMOXIFEN | ChEMBL | Phase 4 (approved) | EGFR |
| TERFENADINE | ChEMBL | Phase 4 (approved) | EGFR |
| THIORIDAZINE | ChEMBL | Phase 4 (approved) | EGFR |
| TRIBROMSALAN | ChEMBL | Phase 4 (approved) | EGFR |
Related Atlas pages
- Genes: EGFR
- Drugs: Afatinib, Selumetinib, Abemaciclib, Acalabrutinib, Alectinib, Astemizole, Axitinib, Bacitracin, Bithionol, Bosutinib, Brigatinib, Cabozantinib, Ceritinib, Chlorpromazine, Chromic Chloride, Cisplatin, Clotrimazole, Colistin, Crizotinib, Dacomitinib, Dasatinib, Dobutamine, Docetaxel, Ebastine, Econazole, Erlotinib, Fedratinib, Fluphenazine, Gefitinib, Gilteritinib, Hexachlorophene, Ibrutinib, Imatinib, Lapatinib, Lazertinib, Levodopa, Lorlatinib, Methyldopa, Miconazole, Midostaurin, Mitoxantrone, Mobocertinib, Montelukast, Nelfinavir, Neratinib, Niclosamide, Olmutinib, Osimertinib, Perhexiline, Ponatinib, Sorafenib, Suloctidil, Sunitinib, Tamoxifen, Terfenadine, Thioridazine, Tribromsalan