◎ Sugi Atlas

Atlas / Drug / Entrectinib

Entrectinib

drug
On this page

Also known as NMS-E628RozlytrekRxdx-101SID103905026EntrecitinibENTRECTINIB (RXDX-101)Entrecinib

Summary

Entrectinib (CHEMBL1983268) is an approved small-molecule antineoplastic agent (ATC L01EX14); indicated across 10 conditions including neoplasm and non-small cell lung carcinoma; with CIViC clinical evidence for 65 variant-indication associations (e.g. NTRK1 Fusion in solid tumor).

At a glance

  • Status: Approved (max clinical phase 4)
  • Modality: Small molecule
  • ATC class: L01EX14
  • Indications: 10 conditions
  • Clinical trials: 33
  • Precision-oncology evidence (CIViC): 65 variant–indication associations
  • Chemistry: 560.6 Da · C31H34F2N6O2

Identifiers

Drug identity and classification

FieldValue
ChEMBL IDCHEMBL1983268
NameEntrectinib
TypeSmall molecule
Max phase4
FDA approvedyes
PubChem CID25141092
ChEBICHEBI:195558
ATCL01EX14
Molecular formulaC31H34F2N6O2
Molecular weight560.6
InChIKeyHAYYBYPASCDWEQ-UHFFFAOYSA-N

SMILES: CN1CCN(CC1)C2=CC(=C(C=C2)C(=O)NC3=NNC4=C3C=C(C=C4)CC5=CC(=CC(=C5)F)F)NC6CCOCC6

IUPAC name: N-[5-[(3,5-difluorophenyl)methyl]-1H-indazol-3-yl]-4-(4-methylpiperazin-1-yl)-2-(oxan-4-ylamino)benzamide

ChEBI definition: A member of the class of indazoles that is 1H-indazole substituted by [4-(4-methylpiperazin-1-yl)-2-(tetrahydro-2H-pyran-4-ylamino)benzoyl]amino and 3,5-difluorobenzyl groups at positions 3 and 5, respectively. It is a potent inhibitor of TRKA, TRKB, TRKC, ROS1, and ALK (IC50 values of 0.1 to 1.7 nM), and used for the treatment of NTRK, ROS1 and ALK gene fusion-positive solid tumours.

Pharmacological roles (ChEBI): antineoplastic agent, EC 2.7.10.1 (receptor protein-tyrosine kinase) inhibitor, antibacterial agent, apoptosis inducer.

Also known as: Entrectinib, NMS-E628, Rozlytrek, Rxdx-101, RXDX-101, SID103905026, ENTRECTINIB, Entrecitinib, ENTRECTINIB (RXDX-101), Entrectinib (RXDX-101), Entrecinib

Patent coverage: 1,431 distinct patent families (3,510 SureChEMBL compound mentions), from 3 matched compound structure(s). One matched structure accounts for 3,107 (89%) 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

Broader ChEMBL bioactivity targets: 64 (assay-derived). Sample: Leucine-rich repeat serine/threonine-protein kinase 2, Tyrosine-protein kinase Fyn, Macrophage colony-stimulating factor 1 receptor, Tyrosine-protein kinase ABL1, Vascular endothelial growth factor receptor 1, Mast/stem cell growth factor receptor Kit, Vascular endothelial growth factor receptor 3, Insulin-like growth factor 1 receptor, Receptor-type tyrosine-protein kinase FLT3, Insulin receptor.

Bioactivity

ChEMBL activities: 180 potent at pChembl ≥ 5 of 180 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):

TargetpChemblTypeValueUnitActivity ID
ROS19.7IC500.2nMCHEMBL_ACT_24797175
NTRK19.66IC500.22nMCHEMBL_ACT_19242642
NTRK19.22IC500.6nMCHEMBL_ACT_27724403
NTRK19.22IC500.6nMCHEMBL_ACT_28452527
NTRK29.13IC500.74nMCHEMBL_ACT_29219829
NTRK19IC501nMCHEMBL_ACT_16586945
NTRK19IC501nMCHEMBL_ACT_24350459
NTRK19IC501nMCHEMBL_ACT_24364007
NTRK19IC501nMCHEMBL_ACT_24797167
NTRK29IC501nMCHEMBL_ACT_24797171
NTRK39IC501nMCHEMBL_ACT_24797173
NTRK19IC501nMCHEMBL_ACT_24839874
NTRK19IC501nMCHEMBL_ACT_24972364
NTRK19IC501nMCHEMBL_ACT_25611325
NTRK19IC501nMCHEMBL_ACT_26023183
NTRK39IC501nMCHEMBL_ACT_26182601
NTRK19IC501nMCHEMBL_ACT_29055508
NTRK19IC501nMCHEMBL_ACT_29263307
ALK9Ki1nMCHEMBL_ACT_9512167
ALK8.8IC501.6nMCHEMBL_ACT_24797176
NTRK38.8Ki1.58nMCHEMBL_ACT_9528225
LTK8.8Ki1.58nMCHEMBL_ACT_9536132
NTRK18.8Ki1.58nMCHEMBL_ACT_9591099
NTRK18.77IC501.7nMCHEMBL_ACT_23155100
NTRK18.77IC501.7nMCHEMBL_ACT_25611372
NTRK38.71IC501.94nMCHEMBL_ACT_29219833
NTRK18.7Kd2nMCHEMBL_ACT_17922627
NTRK18.7IC502nMCHEMBL_ACT_29219803
NTRK28.6Ki2.51nMCHEMBL_ACT_9674265
NTRK18.57IC502.7nMCHEMBL_ACT_23178005

Target pathways

No target-pathway data for this drug (no mapped target genes).

Indications & clinical

Indications

10 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).

IndicationTrial phaseMONDOEFO
neoplasm4MONDO:0005070EFO:0000616
non-small cell lung carcinoma4MONDO:0005233EFO:0003060
cutaneous melanoma2MONDO:0005012EFO:0000389
invasive lobular breast carcinoma2MONDO:0005051EFO:0000553
lymphoid neoplasm2MONDO:0005157EFO:0001642
thyroid gland carcinoma2MONDO:0015075EFO:0002892
central nervous system cancer1MONDO:0002714EFO:0000326
acute myeloid leukemia1MONDO:0018874EFO:0000222
uveal melanoma1MONDO:0006486EFO:1000616

1 further indication record had no mapped disease name (EFO/MeSH-only) or were duplicates, and are omitted.

Clinical trials

Total trials: 33.

Phase distribution

PhaseTrials
PHASE214
PHASE15
Not specified5
PHASE2/PHASE33
PHASE33
PHASE1/PHASE22
EARLY_PHASE11

Top trials by phase / activity

NCTPhaseStatusTitle
NCT03178552PHASE2/PHASE3ACTIVE_NOT_RECRUITINGA Study to Evaluate the Efficacy and Safety of Multiple Targeted Therapies as Treatments for Participants With Non-Small Cell Lung Cancer (NSCLC)
NCT04603807PHASE3ACTIVE_NOT_RECRUITINGA Study to Compare the Efficacy and Safety of Entrectinib and Crizotinib in Participants With Advanced or Metastatic ROS1 Non-small Cell Lung Cancer (NSCLC) With and Without Central Nervous System (CNS) Metastases
NCT05170204PHASE3ACTIVE_NOT_RECRUITINGA Study Evaluating the Efficacy and Safety of Multiple Therapies in Cohorts of Participants With Locally Advanced, Unresectable, Stage III Non-Small Cell Lung Cancer (NSCLC)
NCT05722886PHASE2/PHASE3RECRUITINGDETERMINE (Determining Extended Therapeutic Indications for Existing Drugs in Rare Molecularly Defined Indications Using a National Evaluation Platform Trial) - Master Screening Protocol
NCT05770544PHASE2/PHASE3RECRUITINGDETERMINE Trial Treatment Arm 03: Entrectinib in Adult, Paediatric and Teenage/Young Adult Patients With ROS1 Gene Fusion-Positive Cancers.
NCT05862285PHASE3RECRUITINGA Rollover Study for Participants Previously Enrolled in a Genentech and/or F. Hoffman-La Roche Sponsored Study
NCT02568267PHASE2ACTIVE_NOT_RECRUITINGBasket Study of Entrectinib (RXDX-101) for the Treatment of Patients With Solid Tumors Harboring NTRK 1/2/3 (Trk A/B/C), ROS1, or ALK Gene Rearrangements (Fusions)
NCT02650401PHASE1/PHASE2ACTIVE_NOT_RECRUITINGStudy Of Entrectinib (Rxdx-101) in Children and Adolescents With Locally Advanced Or Metastatic Solid Or Primary CNS Tumors And/Or Who Have No Satisfactory Treatment Options
NCT02925234PHASE2RECRUITINGThe Drug Rediscovery Protocol (DRUP Trial)
NCT03994796PHASE2ACTIVE_NOT_RECRUITINGGenetic Testing in Guiding Treatment for Patients With Brain Metastases
NCT04302025PHASE2RECRUITINGA Study of Multiple Therapies in Biomarker-selected Participants With Resectable Stages IB-III Non-small Cell Lung Cancer (NSCLC)
NCT04589845PHASE2ACTIVE_NOT_RECRUITINGTumor-agnostic Precision Immuno-oncology and Somatic Targeting Rational for You (TAPISTRY) Platform Study
NCT05159245PHASE2RECRUITINGThe Finnish National Study to Facilitate Patient Access to Targeted Anti-cancer Drugs
NCT06482086PHASE2RECRUITINGEfficacy of Organoid-Based Drug Screening to Guide Treatment for Locally Advanced Thyroid Cancer
NCT06528691PHASE2RECRUITINGEntrectinib as a Single Agent in Upfront Therapy for Children <3 Years of Age With NTRK1/2/3 or ROS1-FUSED CNS Tumors
NCT06692491PHASE2NOT_YET_RECRUITINGStudy of Precision Treatment for Rare Tumours in China Guided by PDO and NGS
NCT02587650PHASE2TERMINATEDCapmatinib, Ceritinib, Regorafenib, or Entrectinib in Treating Patients With BRAF/NRAS Wild-Type Stage III-IV Melanoma
NCT03498521PHASE2COMPLETEDA Phase II Randomized Study Comparing the Efficacy and Safety of Targeted Therapy or Cancer Immunotherapy Versus Platinum-Based Chemotherapy in Patients With Cancer of Unknown Primary Site
NCT04551495PHASE2UNKNOWNNeoadjuvant Study of Targeting ROS1 in Combination With Endocrine Therapy in Invasive Lobular Carcinoma of the Breast (ROSALINE)
NCT04589832PHASE1/PHASE2TERMINATEDStudy of PAC-1 and Entrectinib for Patients With Metastatic Uveal Melanoma
NCT04591431PHASE2UNKNOWNThe Rome Trial From Histology to Target: the Road to Personalize Target Therapy and Immunotherapy
NCT04632992PHASE2COMPLETEDA Study Evaluating Targeted Therapies in Participants Who Have Advanced Solid Tumors With Genomic Alterations or Protein Expression Patterns Predictive of Response
NCT05396859PHASE1ACTIVE_NOT_RECRUITINGEntrectinib in Combination With ASTX727 for the Treatment of Relapsed/Refractory TP53 Mutated Acute Myeloid Leukemia
NCT02097810PHASE1COMPLETEDStudy of Oral RXDX-101 in Adult Patients With Locally Advanced or Metastatic Cancer Targeting NTRK1, NTRK2, NTRK3, ROS1, or ALK Molecular Alterations.
NCT03330990PHASE1COMPLETEDEvaluate the Effect of Entrectinib on the Pharmacokinetics of Midazolam in Cancer Patients
NCT03878524PHASE1TERMINATEDSerial Measurements of Molecular and Architectural Responses to Therapy (SMMART) PRIME Trial
NCT04226833PHASE1COMPLETEDA Study to Investigate the Effect of Impaired Hepatic Function on the Pharmacokinetics of Entrectinib in Volunteers With Different Levels of Hepatic Function
NCT05238831EARLY_PHASE1WITHDRAWNSMMART Adaptive Clinical Treatment (ACT) Trial
NCT05525858Not specifiedRECRUITINGKPMNG Study of MOlecular Profiling Guided Therapy Based on Genomic Alterations in Advanced Solid Tumors II
NCT06694129Not specifiedNOT_YET_RECRUITINGReal-world Observational Study of Targeted Therapy in Patients With Advanced ROS1-positive NSCLC
NCT07199959Not specifiedRECRUITINGStudy on the Mechanism of Acquired Resistance of Entrectinib
NCT03066661Not specifiedNO_LONGER_AVAILABLEExpanded Access to Entrectinib for Cancers With NTRK1/2/3, ROS1, or ALK Gene Fusions
NCT05834348Not specifiedCOMPLETEDA Study to Learn About the Effectiveness of Cancer Medicines in Patients With Metastatic Non-small Cell Lung Cancer in Norway.

Clinical evidence (CIViC)

Variant × indication × effect (65 predictive associations from 71 curated evidence items):

VariantIndicationEffectTherapyLevelCIViC
NTRK1 FusionSolid TumorSensitivity/ResponseEntrectinibCIViC AEID11124 +1
ROS1 FusionLung Non-small Cell CarcinomaSensitivity/ResponseEntrectinibCIViC AEID11123 +1
NTRK2 FusionSolid TumorSensitivity/ResponseEntrectinibCIViC AEID11222
NTRK3 FusionSolid TumorSensitivity/ResponseEntrectinibCIViC AEID11125
ALK FusionCancerSensitivity/ResponseEntrectinibCIViC BEID2952
NTRK1 Amplification OR NTRK3 Amplification OR NTRK2 AmplificationCancerSensitivity/ResponseEntrectinibCIViC BEID2958
NTRK1 Fusion OR v::NTRK3 Fusion OR v::NTRK2 FusionSolid TumorSensitivity/ResponseEntrectinibCIViC BEID12071
NTRK3 AmplificationCancerSensitivity/ResponseEntrectinibCIViC BEID2959
NTRK3 FusionCancerSensitivity/ResponseEntrectinibCIViC BEID2949
ETV6::NTRK3 FusionMammary Analogue Secretory CarcinomaSensitivity/ResponseEntrectinibCIViC CEID10692 +1
SQSTM1::NTRK1 FusionLung Non-small Cell CarcinomaSensitivity/ResponseEntrectinibCIViC CEID1868 +1
TFG::ROS1 FusionInflammatory Myofibroblastic TumorSensitivity/ResponseEntrectinibCIViC CEID11860 +1
ALK Alternative Transcript (ATI)Mucosal MelanomaSensitivity/ResponseEntrectinibCIViC CEID7421
ALK F1245VNeuroblastomaSensitivity/ResponseEntrectinibCIViC CEID2987
ALK FusionGastrointestinal CarcinomaSensitivity/ResponseAlectinib + Crizotinib + EntrectinibCIViC CEID10324
ARHGEF2::NTRK1 FusionGlioblastomaSensitivity/ResponseEntrectinibCIViC CEID12606
BCR::NTRK2 FusionBrain Glioblastoma MultiformeSensitivity/ResponseEntrectinibCIViC CEID12035
BCR::NTRK2 FusionGangliogliomaSensitivity/ResponseEntrectinibCIViC CEID12053
CAD::ALK FusionColorectal CancerSensitivity/ResponseEntrectinibCIViC CEID7481
DCTN1::ALK FusionInflammatory Myofibroblastic TumorSensitivity/ResponseEntrectinibCIViC CEID11856
EEF1G::ROS1 FusionDesmoplastic Infantile Ganglioglioma / Desmoplastic Infantile AstrocytomaSensitivity/ResponseEntrectinibCIViC CEID11850
EML1::NTRK2 FusionGangliogliomaSensitivity/ResponseEntrectinibCIViC CEID11852
EML4::ALK FusionHigh Grade GliomaSensitivity/ResponseEntrectinibCIViC CEID12607
EML4::NTRK3 FusionPapillary Thyroid CarcinomaSensitivity/ResponseEntrectinibCIViC CEID10635
EML4::NTRK3 FusionLung Non-small Cell CarcinomaSensitivity/ResponseEntrectinibCIViC CEID10636
EML4::NTRK3 FusionLung AdenocarcinomaSensitivity/ResponseEntrectinibCIViC CEID11099
EML4::NTRK3 FusionCongenital FibrosarcomaSensitivity/ResponseEntrectinibCIViC CEID11859
ETV6::NTRK3 FusionGlioblastomaSensitivity/ResponseEntrectinibCIViC CEID11848
ETV6::NTRK3 FusionAnaplastic AstrocytomaSensitivity/ResponseEntrectinibCIViC CEID11853
ETV6::NTRK3 FusionMelanomaSensitivity/ResponseEntrectinibCIViC CEID11857

+35 more predictive associations (showing top 30 by level).

Pharmacology

Pharmacogenomics

No CPIC/DPWG dosing guideline or drug-level clinical/variant annotations in PharmGKB for this molecule.

No competitor molecules sharing a primary target (ChEMBL phase ≥2 or PubChem drug-class).

About this page

Generated deterministically by Sugi Atlas from primary biomedical databases via BioBTree. Every record on this page traces to a primary source.

Generated
Atlas version
v1.1.2
BioBTree
v2.0.2

Sources 17

This page pulls from 17 datasets indexed by BioBTree:

chebichembl_activitychembl_moleculechembl_targetcivic_evidenceclinical_trialsefogtopdb_interactiongtopdb_ligandhgncmeshmondopatent_compoundpharmgkbpharmgkb_guidelinepubchemuniprot