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.
Click here for help
2D Structure
Click here for help
Click here for structure editor
Physico-chemical Properties
Click here for help
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
Click here for help
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)
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.