afabicin   Click here for help

GtoPdb Ligand ID: 10754

Synonyms: AFN-1720 | Debio 1450 | Debio1450
Compound class: Synthetic organic
Comment: Afabicin (DEBIO 1450) is an inhibitor of bacterial Fabl, the NADH-dependent enoyl reductase from the type II bacterial fatty acid biosynthesis pathway (FAS-II) [3]. This is a prodrug whose active metabolite is DEBIO 1452 (previously AFN-1252) [1].

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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 Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/). 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 9
Hydrogen bond donors 2
Rotatable bonds 8
Topological polar surface area 143.22
Molecular weight 485.14
XLogP 0.53
No. Lipinski's rules broken 0

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)
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.

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)

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Canonical SMILES O=C(N(Cc1oc2c(c1C)cccc2)C)/C=C/c1cnc2c(c1)CCC(=O)N2COP(=O)(O)O
Isomeric SMILES O=C(N(Cc1oc2c(c1C)cccc2)C)/C=C/c1cnc2c(c1)CCC(=O)N2COP(=O)(O)O
InChI InChI=1S/C23H24N3O7P/c1-15-18-5-3-4-6-19(18)33-20(15)13-25(2)21(27)9-7-16-11-17-8-10-22(28)26(23(17)24-12-16)14-32-34(29,30)31/h3-7,9,11-12H,8,10,13-14H2,1-2H3,(H2,29,30,31)/b9-7+
InChI Key HFYMDQMXVPJNTH-VQHVLOKHSA-N

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)
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. Menetrey A, Janin A, Pullman J, Overcash JS, Haouala A, Leylavergne F, Turbe L, Wittke F, Nicolas-Métral V. (2019)
Bone and Joint Tissue Penetration of the Staphylococcus-Selective Antibiotic Afabicin in Patients Undergoing Elective Hip Replacement Surgery.
Antimicrob Agents Chemother, 63 (3). [PMID:30559136]
3. 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]
4. Wittke F, Vincent C, Chen J, Heller B, Kabler H, Overcash JS, Leylavergne F, Dieppois G. (2020)
Afabicin, a First-in-Class Antistaphylococcal Antibiotic, in the Treatment of Acute Bacterial Skin and Skin Structure Infections: Clinical Noninferiority to Vancomycin/Linezolid.
Antimicrob Agents Chemother, 64 (10). [PMID:32747361]