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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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 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
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 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
References
1. Minskaia E, Hertzig T, Gorbalenya AE, Campanacci V, Cambillau C, Canard B, Ziebuhr J. (2006)
Discovery of an RNA virus 3'->5' exoribonuclease that is critically involved in coronavirus RNA synthesis.
Proc Natl Acad Sci USA, 103 (13): 5108-13. [PMID:16549795]
2. Ogando NS, Zevenhoven-Dobbe JC, van der Meer Y, Bredenbeek PJ, Posthuma CC, Snijder EJ. (2020)
The Enzymatic Activity of the nsp14 Exoribonuclease Is Critical for Replication of MERS-CoV and SARS-CoV-2.
J Virol, 94 (23). DOI: 10.1128/JVI.01246-20 [PMID:32938769]
3. Otava T, Šála M, Li F, Fanfrlík J, Devkota K, Perveen S, Chau I, Pakarian P, Hobza P, Vedadi M et al.. (2021)
The Structure-Based Design of SARS-CoV-2 nsp14 Methyltransferase Ligands Yields Nanomolar Inhibitors.
ACS Infect Dis, 7 (8): 2214-2220. [PMID:34152728]
4. Snijder EJ, Decroly E, Ziebuhr J. (2016)
The Nonstructural Proteins Directing Coronavirus RNA Synthesis and Processing.
Adv Virus Res, 96: 59-126. [PMID:27712628]