TO507   Click here for help

GtoPdb Ligand ID: 11981

Synonyms: compound 16 [PMID: 34152728] | TO-507
PDB Ligand
Compound class: Synthetic organic
Comment: TO507 was reported as an inhibitor of the N7-methyltransferase (MTase) RNA capping activity of SARS-CoV-2 nsp14 [3]. It is a derivative of the S-adenosyl-l-homocysteine (SAH) molecule. Nsp14 is one of two MTases in SARS-CoV-2 [1-2,4], and along with other SARS-CoV-2 enzymes (the proteases Mpro and PLpro, RNA-dependent RNA polymerase, helicase, endonuclease and the 2nd MTase nsp16) it is considered as a tractable target for the development of novel antivirals for COVID-19.
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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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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 10
Hydrogen bond donors 5
Rotatable bonds 7
Topological polar surface area 207.93
Molecular weight 534.17
XLogP 0.21
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 OC(=O)[C@H](CCSC[C@H]1O[C@H]([C@@H]([C@@H]1O)O)n1cc(c2c1ncnc2N)C#Cc1cnc2c(c1)cccc2)N
Isomeric SMILES Nc1c2c(ncn1)n(cc2C#Cc1cnc2ccccc2c1)[C@H]1[C@@H]([C@@H]([C@H](O1)CSCC[C@H](N)C(=O)O)O)O
InChI InChI=1S/C26H26N6O5S/c27-17(26(35)36)7-8-38-12-19-21(33)22(34)25(37-19)32-11-16(20-23(28)30-13-31-24(20)32)6-5-14-9-15-3-1-2-4-18(15)29-10-14/h1-4,9-11,13,17,19,21-22,25,33-34H,7-8,12,27H2,(H,35,36)(H2,28,30,31)/t17-,19+,21+,22+,25+/m0/s1
InChI Key SPMFBZXXQBXKFX-LUOSIZPJSA-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
TO507 inhibits human RNA N7-MTase (RNMT: O43148) with an IC50 of 500 nM [3]. It inhibits activity of several human protein methyltransferases (PRMTs), and DNA-MTases such as DOT1L (IC50 5 nM), DNMT3A/3L (IC50 10 nM) and DNMT3B/3L (IC50 30 nM).
Selectivity at other protein targets
Key to terms and symbols Click column headers to sort
Target Sp. Type Action Value Parameter Concentration range (M) Reference
CoV Non-structural protein 14 SARS-CoV-2 Inhibitor Binding 7.6 pKd - 3
⤷ pKd 7.6 (Kd 2.52x10-8 M) [3]
CoV Non-structural protein 14 SARS-CoV-2 Inhibitor Inhibition 8.5 pIC50 - 3
⤷ pIC50 8.5 (IC50 3x10-9 M) [3]
Description: Inhibition of MTase activity