GtoPdb pre-release ligands (2020.2)

These are some of the ligands under curation (pre-release) in the Guide to Pharmacology. We expect them to be available on the website at the next database release (2020.2 – no earlier than April 2020).

  •  Ligand ID: 10716
    • Name: PRD_002214
    • 10716
    • IUPAC: benzyl (2Z,4S)-4-[(2S)-4-methyl-2-[(2S)-3-methyl-2-[(2S)-2-[(5-methyl-1,2-oxazol-3-yl)formamido]propanamido]butanamido]pentanamido]-5-[(3S)-2-oxopyrrolidin-3-yl]pent-2-enoate
    • RCSB PDB: PRD_002214
    • Comment: PRD_002214 is a peptide-like inhibitor of the main protease (MPRO) of SARS-CoV-2. The structure was obtained from the RCSB Protein Data Bank entry 6LU7 which shows the ligand in complex with the protease. The article describing the work has not yet been published (March 12, 2020), but the inhibitor (also referred to as N3) has been deployed in other MPRO crystallisation studies (Yang et al. (2005))

  • Ligand ID: 10720
    • Name: compound 13b
    • Click here for structure editor
    • IUPAC: Tert-butyl (1-((S)-1-(((S)-4-(benzylamino)-3,4-dioxo-1-((S)-2-oxopyrrolidin-3-yl)-butan-2-yl)ami-no)-3-cyclopropyl-1-oxopropan-2-yl)-2-oxo-1,2-dihydropyridin-3-yl)carbamate
    • Comment: Compound 13b is an inhibitor of SARS-CoV-2 main protease (Mpro) [3]. It is a derivative of the prevoiusly reported α-ketoamide inhibitor compound 11r [PMID: 32045235][1]. Compound 13b has an enhanced plasma half-life compared to 11r, plus it exhibits substantial lung tropism and has shown suitability for inhalation-mediated administration.

  • Ligand ID: 10732
      • Name: otamixaban
      • Click here for structure editor
      • IUPAC: methyl (2R,3R)-2-[(3-carbamimidoylphenyl)methyl]-3-[[4-(1-oxidopyridin-1-ium-4-yl)benzoyl]amino]butanoate
      • Comment: Otamixaban (FXV673) is an anticoagulant that was originally reported by Aventis Pharmaceuticals (Sanofi). It is a potent and selective direct inhibitor of coagulation factor Xa that is delivered intravenously. The INN record stipulates the (2R,3R) configuration. Virtual docking studies suggest that otamixaban may bind to the serine protease TMPRSS2, which is linked to host cell entry by a number of viruses, in particular influenza viruses and respiratory viruses such as SARS-CoV-2. Inhibition of TMPRSS2 is being examined for antiviral activity. The TMPRSS2 inhibitory potential and/or antiviral activity of otamixaban have not yet been determined.

  • Ligand ID: 10733
    • Name: I-432
    • Click here for structure editor
    • IUPAC: 3-[(2R)-3-[4-(2-aminoethyl)piperidin-1-yl]-2-[3-(4,6-dichlorocyclohexa-1,5-dien-1-yl)benzenesulfonamido]-3-oxopropyl]benzene-1-carboximidamide
    • Comment: I-432 is an inhibitor of the serine protease TMPRSS2. TMPRSS2, present in human airway cells, is involved in processes that support infection by a number of viruses, thus inhibitors of this protease are being investigated for anti-viral potential

  • Ligand ID: 10735
    • Name: β-D-N4-hydroxycytidine
    • Click here for structure editor
    • IUPAC: 1-[(2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]-4-(hydroxyamino)pyrimidin-2-one
    • Comment: Preliminary evidence from a BioRxiv preprint indicate that the ribonucleoside analog β-D-N4-hydroxycytidine (NHC, EIDD-1931) has broad spectrum antiviral activity against SARS-CoV-2, MERS-CoV, SARS-CoV, and related zoonotic group 2b or 2c Bat-CoVs. The potency of NHC/EIDD-2801 against multiple coronaviruses, its therapeutic efficacy, and oral bioavailability in vivo, all highlight its potential utility as an effective antiviral against SARS-CoV-2 and other future zoonotic coronaviruses.

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