entrectinib   Click here for help

GtoPdb Ligand ID: 8290

Synonyms: NMS-E628 | Rozlytrek® | RXDX-101
Approved drug PDB Ligand
entrectinib is an approved drug (Japan and FDA (2019), EMA (2020))
Compound class: Synthetic organic
Comment: Entrectinib is an oral, brain penetrant, receptor tyrosine kinase (RTK) inhibitor that targets solid tumours that harbour activating alterations in NTRK1, NTRK2, NTRK3 (the Trk family RTKs), ROS1 or ALK [6]. NTRK1 fusion proteins are becoming recognised as oncogenic-drivers in NSCLC [3], so the ability of the compound to target these and ALK- and ROS1-rearrangements suggests it has the potential to become a useful oncology agent.
More recently entrectinib has been shown to inhibit NLRP3 inflammasome assembly and activation via a direct interaction with NIMA related kinase 7 (NEK7) that disrupts the NLRP3-NEK7 interaction [5]. This discovery suggests a role for entrectinib as an intervention for inflammasome-related diseases.
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Ligand Activity Visualisation Charts

These are box plot that provide a unique visualisation, summarising all the activity data for a ligand taken from ChEMBL and GtoPdb across multiple targets and species. Click on a plot to see the median, interquartile range, low and high data points. A value of zero indicates that no data are available. A separate chart is created for each target, and where possible the algorithm tries to merge ChEMBL and GtoPdb targets by matching them on name and UniProt accession, for each available species. However, please note that inconsistency in naming of targets may lead to data for the same target being reported across multiple charts.

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View interactive charts of activity data across species
2D Structure
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2D Structure

An image of the ligand's 2D structure. For small molecules with SMILES these are drawn using the NCI/CADD Chemical Identifier Resolver. Click on the image to access the chemical structure search tool with the ligand pre-loaded in the structure editor. For other types of ligands, e.g. longer nucleotides and peptides, a manually drawn representation of the molecule may be provided.

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Physico-chemical Properties
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Physico-chemical Properties

Calculated molecular properties are available for small molecules and natural products (not peptides). Properties were generated using the CDK toolkit. All properties were selected to enable the prediction of the Lipinski Rule-of-Five profile or ‘druglikeness’ for each ligand. For more info on each category see the help pages.

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Hydrogen bond acceptors 7
Hydrogen bond donors 3
Rotatable bonds 8
Topological polar surface area 85.52
Molecular weight 560.27
XLogP 6.13
No. Lipinski's rules broken 1
SMILES / InChI / InChIKey
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SMILES / InChI / InChIKey

SMILES (Simplified Molecular Input Line Entry Specification) A specification for unambiguously describing the structure of chemical molecules using short ASCII strings. Canonical SMILES specify a unique representation of the 2D structure without chiral or isotopic specifications. Isomeric SMILES include chiral specification and isotopes.

Standard InChI (IUPAC International Chemical Identifier) and InChIKey InChI is a non-proprietary, standard, textual identifier for chemical substances designed to facilitate linking of information and database searching. An InChIKey is a simplified version of a full InChI, designed for easier web searching.

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Canonical SMILES CN1CCN(CC1)c1ccc(c(c1)NC1CCOCC1)C(=O)Nc1n[nH]c2c1cc(cc2)Cc1cc(F)cc(c1)F
Isomeric SMILES CN1CCN(CC1)c1ccc(c(c1)NC1CCOCC1)C(=O)Nc1n[nH]c2c1cc(cc2)Cc1cc(F)cc(c1)F
InChI InChI=1S/C31H34F2N6O2/c1-38-8-10-39(11-9-38)25-3-4-26(29(19-25)34-24-6-12-41-13-7-24)31(40)35-30-27-17-20(2-5-28(27)36-37-30)14-21-15-22(32)18-23(33)16-21/h2-5,15-19,24,34H,6-14H2,1H3,(H2,35,36,37,40)
InChI Key HAYYBYPASCDWEQ-UHFFFAOYSA-N
Classification Click here for help
Compound class Synthetic organic
Approved drug? Yes (Japan and FDA (2019), EMA (2020))
IUPAC Name Click here for help
N-[5-[(3,5-difluorophenyl)methyl]-1H-indazol-3-yl]-4-(4-methylpiperazin-1-yl)-2-(oxan-4-ylamino)benzamide
International Nonproprietary Names Click here for help
INN number INN
10132 entrectinib
Synonyms Click here for help
NMS-E628 | Rozlytrek® | RXDX-101
Database Links Click here for help
CAS Registry No. 1108743-60-7
ChEMBL Ligand CHEMBL1983268
DrugCentral Ligand 5345
GtoPdb PubChem SID 252166502
PubChem CID 25141092
RCSB PDB Ligand YMX
Search Google for chemical match using the InChIKey HAYYBYPASCDWEQ-UHFFFAOYSA-N
Search Google for chemicals with the same backbone HAYYBYPASCDWEQ
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UniChem Compound Search for chemical match using the InChIKey HAYYBYPASCDWEQ-UHFFFAOYSA-N
UniChem Connectivity Search for chemical match using the InChIKey HAYYBYPASCDWEQ-UHFFFAOYSA-N