V2043   Click here for help

GtoPdb Ligand ID: 12587

Synonyms: 1-O-Octadecyl-2-O-benzyl-sn-glyceryl-3-phospho-GS-441524 | compound 5c [PMID: 34310217] | example 67 [WO2022081973A1] | ODBG-P-RVn
Compound class: Synthetic organic
Comment: V2043 is an orally bioavailable phospholipid analogue of remdesivir nucleoside (RVn; GS-441524) [1,3]. It is a prodrug that is metabolised first to RVn monophosphate (by sphingomyelin phosphodiesterase I), and then to the active metabolite RVn triphosphate. Mechanistically, RVn triphosphate inhibits the viral RNA-dependent RNA polymerase (RdRP). Antiviral activity against SARS-CoV-2 has been demonstrated in vitro and in a mouse model of SARS-CoV-2 infection. Structural modifications of V2043 have been reported to improve its antiviral activity [1].
2D Structure
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Physico-chemical Properties
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Hydrogen bond acceptors 14
Hydrogen bond donors 4
Rotatable bonds 29
Topological polar surface area 211.49
Molecular weight 787.92
XLogP 6.39
No. Lipinski's rules broken 4
SMILES / InChI / InChIKey
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Canonical SMILES CCCCCCCCCCCCCCCCCCOC[C@H](COP(=O)(O)OC[C@@H]1[C@H]([C@H]([C@](C#N)(C2=CC=C3C(=NC=NN32)N)O1)O)O)OCC4=CC=CC=C4
Isomeric SMILES P(=O)(OC[C@H]1O[C@@]([C@@H]([C@@H]1O)O)(C#N)C2=CC=C3C(=NC=NN32)N)(OC[C@@H](COCCCCCCCCCCCCCCCCCC)OCC4=CC=CC=C4)O
InChI InChI=1S/C40H62N5O9P/c1-2-3-4-5-6-7-8-9-10-11-12-13-14-15-16-20-25-50-27-33(51-26-32-21-18-17-19-22-32)28-52-55(48,49)53-29-35-37(46)38(47)40(30-41,54-35)36-24-23-34-39(42)43-31-44-45(34)36/h17-19,21-24,31,33,35,37-38,46-47H,2-16,20,25-29H2,1H3,(H,48,49)(H2,42,43,44)/t33-,35-,37-,38-,40+/m1/s1
InChI Key JWTGVUMJEVOXGW-RTZKIGCUSA-N
Bioactivity Comments
In vitro antiviral activity against several SARS-CoV-2 variants has been demonstrated: B.1.1.7 (Alpha; EC50 146 nM), B.1.351 (Beta; EC50 146 nM), P.1 (Gamma; EC50 167 nM), B.1.617.2 (Delta; EC50 85 nM), BA.1 (Omicron; EC50 44 nM) [1]. Evidence of anti-RSV activity was contained in Gilead Sciences' patent WO2022081973A1 [2]. As a prodrug, target potency will be associated with the active metabolite RVn triphosphate.
Selectivity at other protein targets
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Target Sp. Type Action Value Parameter Concentration range (M) Reference
CoV RNA-dependent RNA polymerase SARS-CoV Inhibitor Inhibition - - -