tucatinib   Click here for help

GtoPdb Ligand ID: 9922

Synonyms: ARRY-380 | Example 11 [WO2007059257A2] | ONT-380 | Tukysa®
Approved drug
tucatinib is an approved drug (FDA (2020), EMA (2021))
Compound class: Synthetic organic
Comment: Tucatinib is an orally bioavailable ERBB2 (HER2) receptor tyrosine kinase inhibitor that was developed as a novel antineoplastic agent by Seattle Genetics [2]. The chemical structure is claimed as Example 11 in Array Biopharma patent WO2007059257A2 [3], and was exemplified as ARRY-380 in the later patent WO2013056183A1 [1]. Tucatinib contains a quinazoline core that is conserved in other tyrosine kinase inhibitors including lapatinib, erlotinib, and gefitinib [2].
The INN tucatinib replaced the earlier INN irbinitinib that was associated with this chemical entity.
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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 8
Hydrogen bond donors 2
Rotatable bonds 6
Topological polar surface area 110.85
Molecular weight 480.2
XLogP 3.75
No. Lipinski's rules broken 0
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 Cc1cc(ccc1Oc1ccn2c(c1)ncn2)Nc1ncnc2c1cc(cc2)NC1=NC(CO1)(C)C
Isomeric SMILES Cc1cc(ccc1Oc1ccn2c(c1)ncn2)Nc1ncnc2c1cc(cc2)NC1=NC(CO1)(C)C
InChI InChI=1S/C26H24N8O2/c1-16-10-17(5-7-22(16)36-19-8-9-34-23(12-19)28-15-30-34)31-24-20-11-18(4-6-21(20)27-14-29-24)32-25-33-26(2,3)13-35-25/h4-12,14-15H,13H2,1-3H3,(H,32,33)(H,27,29,31)
InChI Key SDEAXTCZPQIFQM-UHFFFAOYSA-N
No information available.
Summary of Clinical Use Click here for help
Early clinical trial data indicated that tucatinib produced marked antitumour activity in heavily pretreated HER2+ve metastatic breast cancer patients, and some of the side effects were diminished in comparison to contemporary dual HER2/EGFR inhibitors [4]. Several Phase 2 studies in breast cancer and other cancers with ERBB2 gene amplification were undertaken. Click here to link to the complete list of tucatinib trials that are registered at ClinicalTrials.gov.
A FDA New Drug Application for tucatinib for locally advanced or metastatic HER2+ve breast cancer was submitted by Seattle Genetics in December 2019. The first full FDA approval was granted in April 2020. Under this approval tucatinib was indicated for advanced unresectable or metastatic HER2+ve breast cancer (including brain metastases) in combination with trastuzumab and capecitabine, in patients who had received ≥1 prior anti-HER2-based regimens for metastatic disease. In early 2023, the FDA issued accelerated approval for combined treatment with tucatinib plus trastuzumab for colorectal cancer (specifically for RAS wild-type HER2-positive unresectable or metastatic colorectal cancer), that has progressed after FOLFOXIRI chemotherapy (a fluoropyrimidine, oxaliplatin, and irinotecan). This decision was based on data from the MOUNTAINEER study (NCT03043313).
Clinical Trials
Clinical Trial ID Title Type Source Comment References
NCT03043313 Tucatinib Plus Trastuzumab in Patients With HER2+ Colorectal Cancer Phase 2 Interventional Seagen Inc.