Afabicin

Afabicin
Clinical data
Other names	AFN-1720; Debio1450
Legal status
Legal status	Investigational;
Identifiers
	IUPAC name [6-[(E)-3-[methyl-[(3-methyl-1-benzofuran-2-yl)methyl]amino]-3-oxoprop-1-enyl]-2-oxo-3,4-dihydro-1,8-naphthyridin-1-yl]methyl dihydrogen phosphate;
CAS Number	1518800-35-5;
PubChem CID	72696796;
IUPHAR/BPS	10754;
DrugBank	DB15268;
ChemSpider	58827798;
UNII	DMM8663H2R;
ChEMBL	ChEMBL4297501;
Chemical and physical data
Formula	C23H24N3O7P
Molar mass	485.433 g·mol−1
3D model (JSmol)	Interactive image;
	SMILES CC1=C(OC2=CC=CC=C12)CN(C)C(=O)/C=C/C3=CC4=C(N=C3)N(C(=O)CC4)COP(=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+; Key:HFYMDQMXVPJNTH-VQHVLOKHSA-N;

Afabicin (Debio 1450) is an experimental antibiotic developed by Debiopharm for the treatment of Staphylococcus aureus infections. It is a prodrug which is converted in vivo into the active form afabicin desphosphono (Debio 1452) which acts as an inhibitor of the staphylococcal enoyl-acyl carrier protein reductase (FabI) enzyme. It has shown similar efficacy in clinical trials to established drugs such as vancomycin, but has not yet been approved for clinical use.^[1]^[2]^[3]^[4]^[5]^[6]

References

^ Menetrey A, Janin A, Pullman J, Overcash JS, Haouala A, Leylavergne F, et al. (March 2019). "Bone and Joint Tissue Penetration of the Staphylococcus-Selective Antibiotic Afabicin in Patients Undergoing Elective Hip Replacement Surgery". Antimicrobial Agents and Chemotherapy. 63 (3). doi:10.1128/AAC.01669-18. PMC 6395911. PMID 30559136.
^ Bassetti M, Del Puente F, Magnasco L, Giacobbe DR (May 2020). "Innovative therapies for acute bacterial skin and skin-structure infections (ABSSSI) caused by methicillin-resistant Staphylococcus aureus: advances in phase I and II trials". Expert Opinion on Investigational Drugs. 29 (5): 495–506. doi:10.1080/13543784.2020.1750595. PMID 32242469.
^ Wittke F, Vincent C, Chen J, Heller B, Kabler H, Overcash JS, et al. (September 2020). "Afabicin, a First-in-Class Antistaphylococcal Antibiotic, in the Treatment of Acute Bacterial Skin and Skin Structure Infections: Clinical Noninferiority to Vancomycin/Linezolid". Antimicrobial Agents and Chemotherapy. 64 (10). doi:10.1128/AAC.00250-20. PMC 7508579. PMID 32747361.
^ Ruggieri F, Compagne N, Antraygues K, Eveque M, Flipo M, Willand N (August 2023). "Antibiotics with novel mode of action as new weapons to fight antimicrobial resistance". European Journal of Medicinal Chemistry. 256: 115413. doi:10.1016/j.ejmech.2023.115413. PMID 37150058.
^ Bibens L, Becker JP, Dassonville-Klimpt A, Sonnet P (March 2023). "A Review of Fatty Acid Biosynthesis Enzyme Inhibitors as Promising Antimicrobial Drugs". Pharmaceuticals. 16 (3): 425. doi:10.3390/ph16030425. PMC 10054515. PMID 36986522.
^ Nowakowska J, Cameron DR, De Martino A, Kühn J, Le Fresne-Languille S, Leuillet S, et al. (August 2023). "Evaluation of the microbiota-sparing properties of the anti-staphylococcal antibiotic afabicin". The Journal of Antimicrobial Chemotherapy. 78 (8): 1900–1908. doi:10.1093/jac/dkad181. PMC 10393889. PMID 37294305.

[1] Menetrey A, Janin A, Pullman J, Overcash JS, Haouala A, Leylavergne F, et al. (March 2019). "Bone and Joint Tissue Penetration of the Staphylococcus-Selective Antibiotic Afabicin in Patients Undergoing Elective Hip Replacement Surgery". Antimicrobial Agents and Chemotherapy. 63 (3). doi:10.1128/AAC.01669-18. PMC 6395911. PMID 30559136.

[2] Bassetti M, Del Puente F, Magnasco L, Giacobbe DR (May 2020). "Innovative therapies for acute bacterial skin and skin-structure infections (ABSSSI) caused by methicillin-resistant Staphylococcus aureus: advances in phase I and II trials". Expert Opinion on Investigational Drugs. 29 (5): 495–506. doi:10.1080/13543784.2020.1750595. PMID 32242469.

[3] Wittke F, Vincent C, Chen J, Heller B, Kabler H, Overcash JS, et al. (September 2020). "Afabicin, a First-in-Class Antistaphylococcal Antibiotic, in the Treatment of Acute Bacterial Skin and Skin Structure Infections: Clinical Noninferiority to Vancomycin/Linezolid". Antimicrobial Agents and Chemotherapy. 64 (10). doi:10.1128/AAC.00250-20. PMC 7508579. PMID 32747361.

[4] Ruggieri F, Compagne N, Antraygues K, Eveque M, Flipo M, Willand N (August 2023). "Antibiotics with novel mode of action as new weapons to fight antimicrobial resistance". European Journal of Medicinal Chemistry. 256: 115413. doi:10.1016/j.ejmech.2023.115413. PMID 37150058.

[5] Bibens L, Becker JP, Dassonville-Klimpt A, Sonnet P (March 2023). "A Review of Fatty Acid Biosynthesis Enzyme Inhibitors as Promising Antimicrobial Drugs". Pharmaceuticals. 16 (3): 425. doi:10.3390/ph16030425. PMC 10054515. PMID 36986522.

[6] Nowakowska J, Cameron DR, De Martino A, Kühn J, Le Fresne-Languille S, Leuillet S, et al. (August 2023). "Evaluation of the microbiota-sparing properties of the anti-staphylococcal antibiotic afabicin". The Journal of Antimicrobial Chemotherapy. 78 (8): 1900–1908. doi:10.1093/jac/dkad181. PMC 10393889. PMID 37294305.

[1]

[2]

[3]

[4]

[5]

[6]

Afabicin

See also

References