zotiraciclib   Click here for help

GtoPdb Ligand ID: 9095

Synonyms: compound 26h [PMID: 22148278] | SB-1317 | SB1317 | TG-02 | TG02
Compound class: Synthetic organic
Comment: Zotiraciclib (TG02) is an orally active multi-kinase inhibitor, with a unique activity profile against CDKs, JAK2 and FLT3 [4-5]. Like pacritinib it is a small molecule macrocycle. TG02 was rationally designed to simultaneously inhibit several key signalling pathways, with the aim of maximising anti-cancer efficacy. It is being investigated for its anti-leukemic potential [2-3].
The compound is administered as the citrate salt.
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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

zotiraciclib 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 4
Hydrogen bond donors 1
Rotatable bonds 0
Topological polar surface area 50.28
Molecular weight 372.2
XLogP 4.29
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 CN1CC=CCCOc2cccc(c2)c2nc(Nc3cc(C1)ccc3)ncc2
Isomeric SMILES CN1C/C=C/CCOc2cccc(c2)c2nc(Nc3cc(C1)ccc3)ncc2
InChI InChI=1S/C23H24N4O/c1-27-13-3-2-4-14-28-21-10-6-8-19(16-21)22-11-12-24-23(26-22)25-20-9-5-7-18(15-20)17-27/h2-3,5-12,15-16H,4,13-14,17H2,1H3,(H,24,25,26)/b3-2+
InChI Key VXBAJLGYBMTJCY-NSCUHMNNSA-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
In a kinase profiling study TG02 was found to inhibit 17 of the 63 kinases tested [1]. Eleven of the 17 positive hits were against CDK/JAK/FLT family members. Some of the other kinases inhibited by TG02 are implicated in inflammatory and proliferative processes (e.g. Lck, Fyn, Fms (CSF1R), TYRO3, ERK5, and p38δ). TG02 most potently inhibited CDK isoforms (IC50s 3-9 nM for CDKs 1,2,3,5 and 9 and IC50 of 37 nM for CDK7). CDK6 was less potently inhibited (IC50 113 nM). CDK4 was not significantly inhibited. The Janus kinase family members JAK1, JAK2 and TYK2 were potently inhibited but JAK3 was not. Class III receptor tyrosine kinases Fms and Fms-like tyrosine kinase 3 (FLT3) were potently inhibited, as were the src family kinases Lck and Fyn (but not Src itself), and the MAPK family members ERK5 and p38δ.
Selectivity at enzymes
Key to terms and symbols Click column headers to sort
Target Sp. Type Action Value Parameter Concentration range (M) Reference
cyclin dependent kinase 9 Hs Inhibitor Inhibition 8.5 pIC50 - 1
⤷ pIC50 8.5 (IC50 3x10-9 M) [1]
cyclin dependent kinase 5 Hs Inhibitor Inhibition 8.4 pIC50 - 1
⤷ pIC50 8.4 (IC50 4x10-9 M) [1]
cyclin dependent kinase 3 Hs Inhibitor Inhibition 8.1 pIC50 - 1
⤷ pIC50 8.1 (IC50 8x10-9 M) [1]
cyclin dependent kinase 2 Hs Inhibitor Inhibition 7.9 – 8.3 pIC50 - 1,5
⤷ pIC50 7.9 – 8.3 (IC50 1.3x10-8 – 5x10-9 M) [1,5]
cyclin dependent kinase 1 Hs Inhibitor Inhibition 8.1 pIC50 - 1
⤷ pIC50 8.1 (IC50 9x10-9 M) [1]
tyrosine kinase 2 Hs Inhibitor Inhibition 7.8 pIC50 - 1
⤷ pIC50 7.8 (IC50 1.4x10-8 M) [1]
Janus kinase 2 Hs Inhibitor Inhibition 7.1 – 7.7 pIC50 - 1,5
⤷ pIC50 7.1 – 7.7 (IC50 7.3x10-8 – 1.9x10-8 M) [1,5]
Janus kinase 1 Hs Inhibitor Inhibition 7.2 pIC50 - 1
⤷ pIC50 7.2 (IC50 5.9x10-8 M) [1]
Selectivity at catalytic receptors
Key to terms and symbols Click column headers to sort
Target Sp. Type Action Value Parameter Concentration range (M) Reference
colony stimulating factor 1 receptor Hs Inhibitor Inhibition 7.6 pIC50 - 1
⤷ pIC50 7.6 (IC50 2.7x10-8 M) [1]
fms related receptor tyrosine kinase 3 Hs Inhibitor Inhibition 7.3 – 7.7 pIC50 - 1,5
⤷ pIC50 7.3 – 7.7 (IC50 5.6x10-8 – 1.9x10-8 M) [1,5]