TO507   Click here for help

GtoPdb Ligand ID: 11981

Synonyms: compound 16 [PMID: 34152728] | TO-507
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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2D Structure
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Physico-chemical Properties
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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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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]