DEBIO 1452   Click here for help

GtoPdb Ligand ID: 10755

Synonyms: afabicin desphosphono | AFN-1252 | AFN-12520000 | DEBIO-1452 | DEBIO1452
Compound class: Synthetic organic
Comment: DEBIO 1452 (previously AFN-1252) is the active metabolite of afabicin (DEBIO 1450) [3]. It is an inhibitor of bacterial Fabl, the NADH-dependent enoyl reductase from the type II bacterial fatty acid biosynthesis pathway (FAS-II) [1-2]. It specifically targets staphylococci without significant activity against other Gram +ve or Gram -ve species [2].
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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 5
Hydrogen bond donors 1
Rotatable bonds 5
Topological polar surface area 75.44
Molecular weight 375.16
XLogP 2.19
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 O=C1CCc2c(N1)ncc(c2)/C=C/C(=O)N(Cc1oc2c(c1C)cccc2)C
Isomeric SMILES O=C1CCc2c(N1)ncc(c2)/C=C/C(=O)N(Cc1oc2c(c1C)cccc2)C
InChI InChI=1S/C22H21N3O3/c1-14-17-5-3-4-6-18(17)28-19(14)13-25(2)21(27)10-7-15-11-16-8-9-20(26)24-22(16)23-12-15/h3-7,10-12H,8-9,13H2,1-2H3,(H,23,24,26)/b10-7+
InChI Key QXTWSUQCXCWEHF-JXMROGBWSA-N
References
1. Flamm RK, Rhomberg PR, Kaplan N, Jones RN, Farrell DJ. (2015)
Activity of Debio1452, a FabI inhibitor with potent activity against Staphylococcus aureus and coagulase-negative Staphylococcus spp., including multidrug-resistant strains.
Antimicrob Agents Chemother, 59 (5): 2583-7. [PMID:25691627]
2. Peyrusson F, Van Wessem A, Dieppois G, Van Bambeke F, Tulkens PM. (2020)
Cellular pharmacokinetics and intracellular activity of the bacterial fatty acid synthesis inhibitor, afabicin desphosphono against different resistance phenotypes of Staphylococcus aureus in models of cultured phagocytic cells.
Int J Antimicrob Agents, 55 (2): 105848. [PMID:31770623]
3. Ross JE, Flamm RK, Jones RN. (2015)
Initial broth microdilution quality control guidelines for Debio 1452, a FabI inhibitor antimicrobial agent.
Antimicrob Agents Chemother, 59 (11): 7151-2. [PMID:26324261]