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

tirbanibulin is commercially available from our sponsors

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 Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/). 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

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)
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.

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)

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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

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)
Bioactivity Comments
The binding affinity of KX2-391 for isolated Src protien is low [8]. However, KX2-391 inhibits both auto- and trans-phosphorylation activites mediated by Src, and these correlate with the potency of growth inhibition observed in whole cells. Although an IC50 value of 20nM for inhibition of Src activity by KX2-391 is referred to in articles such as [6] and [7], we have been unable to find the primary source of this data.
Several articles demonstrate the effectiveness of KX2-391 as an inhibitor of tumour cell proliferation both in vitro and in vivo [1,3-4], and indeed this compound showed preliminary signs of clinical efficacy against solid tumours in a Phase I study [6]. Patent data (US20060160800 [2]) provides GI50 values of 13nM and 26nM for growth inhibition of c-Src 3T3 cells and HT-29 cells respectively. α and β tubulin binding was shown using a photoaffinity analogue of KX2-391 [8].
Selectivity at enzymes
Key to terms and symbols Click column headers to sort
Target Sp. Type Action Value Parameter Concentration range (M) Reference
SRC proto-oncogene, non-receptor tyrosine kinase Hs Inhibitor Inhibition 4.3 pIC50 - 8
⤷ pIC50 4.3 (IC50 4.6x10-5 M) [8]
Description: Low affinity is expected because the peptide substrate binding site is not well formed when Src is isolated.