tirbanibulin   Click here for help

GtoPdb Ligand ID: 7957

Synonyms: Klisyri® | KX 2-391 | KX-01 | KX-2-391 | KX2-391
Approved drug PDB Ligand
tirbanibulin is an approved drug (FDA (2020), EMA (2021))
Compound class: Synthetic organic
Comment: Tirbanibulin (KX2-391) is an orally bioavailable small molecule with a dual mode of action. It is a Src kinase inhibitor with potential antiproliferative activity [7-8] and an inhibitor of tubulin polymerization [8].
Synthesis of KX2-391 is described in US patent US20060160800 [2], where it is compound 134.
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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 5
Hydrogen bond donors 1
Rotatable bonds 10
Topological polar surface area 63.69
Molecular weight 431.22
XLogP 3.09
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 O=C(Cc1ccc(cn1)c1ccc(cc1)OCCN1CCOCC1)NCc1ccccc1
Isomeric SMILES O=C(Cc1ccc(cn1)c1ccc(cc1)OCCN1CCOCC1)NCc1ccccc1
InChI InChI=1S/C26H29N3O3/c30-26(28-19-21-4-2-1-3-5-21)18-24-9-6-23(20-27-24)22-7-10-25(11-8-22)32-17-14-29-12-15-31-16-13-29/h1-11,20H,12-19H2,(H,28,30)
InChI Key HUNGUWOZPQBXGX-UHFFFAOYSA-N
No information available.
Summary of Clinical Use Click here for help
Tirbanibulin (KX2-391) was advanced to Phase 3 clinical trial as a potential topically applied treatment for actinic keratoses (see NCT03285490). It has also completed early stage trials in solid and hematological malignancies. The first approval was for use as a treatment for actinic keratosis (of the face or scalp), granted by the FDA in December 2020 [5]. EMA approval for this indication followed in July 2021.
Mechanism Of Action and Pharmacodynamic Effects Click here for help
KX2-391 is a peptidomimetic, which binds to the peptide substrate binding site of Src kinase rather than to the ATP-binding site, which is likely to increase target specificity.
Clinical Trials
Clinical Trial ID Title Type Source Comment References
NCT03285490 A Multi-Center Study to Evaluate the Efficacy and Safety of KX2-391 Ointment 1% on AK on Face or Scalp (AK004) Phase 3 Interventional Athenex, Inc.