Afabicin

Last updated

Afabicin
Afabicin.svg
Clinical data
Other namesAFN-1720; Debio1450
Legal status
Legal status
  • Investigational
Identifiers
  • [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
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
ChEMBL
Chemical and physical data
Formula C23H24N3O7P
Molar mass 485.433 g·mol−1
3D model (JSmol)
  • 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=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]

See also

Related Research Articles

<i>Staphylococcus aureus</i> Species of gram-positive bacterium

Staphylococcus aureus is a gram-positive spherically shaped bacterium, a member of the Bacillota, and is a usual member of the microbiota of the body, frequently found in the upper respiratory tract and on the skin. It is often positive for catalase and nitrate reduction and is a facultative anaerobe, meaning that it can grow without oxygen. Although S. aureus usually acts as a commensal of the human microbiota, it can also become an opportunistic pathogen, being a common cause of skin infections including abscesses, respiratory infections such as sinusitis, and food poisoning. Pathogenic strains often promote infections by producing virulence factors such as potent protein toxins, and the expression of a cell-surface protein that binds and inactivates antibodies. S. aureus is one of the leading pathogens for deaths associated with antimicrobial resistance and the emergence of antibiotic-resistant strains, such as methicillin-resistant S. aureus (MRSA). The bacterium is a worldwide problem in clinical medicine. Despite much research and development, no vaccine for S. aureus has been approved.

<span class="mw-page-title-main">Vancomycin</span> Antibiotic medication

Vancomycin is a glycopeptide antibiotic medication used to treat certain bacterial infections. It is administered intravenously to treat complicated skin infections, bloodstream infections, endocarditis, bone and joint infections, and meningitis caused by methicillin-resistant Staphylococcus aureus. Blood levels may be measured to determine the correct dose. Vancomycin is also taken orally to treat severe Clostridium difficile colitis. Taken orally, it is poorly absorbed.

Methicillin-resistant <i>Staphylococcus aureus</i> Bacterium responsible for difficult-to-treat infections in humans

Methicillin-resistant Staphylococcus aureus (MRSA) is a group of gram-positive bacteria that are genetically distinct from other strains of Staphylococcus aureus. MRSA is responsible for several difficult-to-treat infections in humans. It caused more than 100,000 deaths worldwide attributable to antimicrobial resistance in 2019.

<span class="mw-page-title-main">Linezolid</span> Antibiotic medication

Linezolid is an antibiotic used for the treatment of infections caused by Gram-positive bacteria that are resistant to other antibiotics. Linezolid is active against most Gram-positive bacteria that cause disease, including streptococci, vancomycin-resistant enterococci (VRE), and methicillin-resistant Staphylococcus aureus (MRSA). The main uses are infections of the skin and pneumonia although it may be used for a variety of other infections including drug-resistant tuberculosis. It is used either by injection into a vein or by mouth.

Vancomycin-resistant <i>Staphylococcus aureus</i> Antibiotica resistant bacteria

Vancomycin-resistant Staphylococcus aureus (VRSA) are strains of Staphylococcus aureus that have acquired resistance to the glycopeptide antibiotic vancomycin. Bacteria can acquire resistant genes either by random mutation or through the transfer of DNA from one bacterium to another. Resistance genes interfere with the normal antibiotic function and allow bacteria to grow in the presence of the antibiotic. Resistance in VRSA is conferred by the plasmid-mediated vanA gene and operon. Although VRSA infections are uncommon, VRSA is often resistant to other types of antibiotics and a potential threat to public health because treatment options are limited. VRSA is resistant to many of the standard drugs used to treat S. aureus infections. Furthermore, resistance can be transferred from one bacterium to another.

<i>Staphylococcus haemolyticus</i> Species of bacterium

Staphylococcus haemolyticus is a member of the coagulase-negative staphylococci (CoNS). It is part of the skin flora of humans, and its largest populations are usually found at the axillae, perineum, and inguinal areas. S. haemolyticus also colonizes primates and domestic animals. It is a well-known opportunistic pathogen, and is the second-most frequently isolated CoNS. Infections can be localized or systemic, and are often associated with the insertion of medical devices. The highly antibiotic-resistant phenotype and ability to form biofilms make S. haemolyticus a difficult pathogen to treat. Its most closely related species is Staphylococcus borealis.

<span class="mw-page-title-main">Piperacillin</span> Antibiotic medication

Piperacillin is a broad-spectrum β-lactam antibiotic of the ureidopenicillin class. The chemical structure of piperacillin and other ureidopenicillins incorporates a polar side chain that enhances penetration into Gram-negative bacteria and reduces susceptibility to cleavage by Gram-negative beta lactamase enzymes. These properties confer activity against the important hospital pathogen Pseudomonas aeruginosa. Thus piperacillin is sometimes referred to as an "anti-pseudomonal penicillin".

<span class="mw-page-title-main">Oritavancin</span> Pharmaceutical drug

Oritavancin, sold under the brand name Orbactiv among others, is a semisynthetic glycopeptide antibiotic medication for the treatment of serious Gram-positive bacterial infections. Its chemical structure as a lipoglycopeptide is similar to vancomycin.

Lysostaphin is a Staphylococcus simulans metalloendopeptidase. It can function as a bacteriocin (antimicrobial) against Staphylococcus aureus.

β-Lactamase inhibitor Drugs that inhibit β-Lactamase enzymes

Beta-lactamases are a family of enzymes involved in bacterial resistance to beta-lactam antibiotics. In bacterial resistance to beta-lactam antibiotics, the bacteria have beta-lactamase which degrade the beta-lactam rings, rendering the antibiotic ineffective. However, with beta-lactamase inhibitors, these enzymes on the bacteria are inhibited, thus allowing the antibiotic to take effect. Strategies for combating this form of resistance have included the development of new beta-lactam antibiotics that are more resistant to cleavage and the development of the class of enzyme inhibitors called beta-lactamase inhibitors. Although β-lactamase inhibitors have little antibiotic activity of their own, they prevent bacterial degradation of beta-lactam antibiotics and thus extend the range of bacteria the drugs are effective against.

<span class="mw-page-title-main">Ceftobiprole</span> Chemical compound

Ceftobiprole, sold under the brand name Zevtera among others, is a fifth-generation cephalosporin antibacterial used for the treatment of hospital-acquired pneumonia and community-acquired pneumonia. It is marketed by Basilea Pharmaceutica under the brand names Zevtera and Mabelio. Like other cephalosporins, ceftobiprole exerts its antibacterial activity by binding to important penicillin-binding proteins and inhibiting their transpeptidase activity which is essential for the synthesis of bacterial cell walls. Ceftobiprole has high affinity for penicillin-binding protein 2a of methicillin-resistant Staphylococcus aureus strains and retains its activity against strains that express divergent mecA gene homologues. Ceftobiprole also binds to penicillin-binding protein 2b in Streptococcus pneumoniae (penicillin-intermediate), to penicillin-binding protein 2x in Streptococcus pneumoniae (penicillin-resistant), and to penicillin-binding protein 5 in Enterococcus faecalis.

<span class="mw-page-title-main">Telavancin</span> Pharmaceutical drug

Telavancin is a bactericidal lipoglycopeptide for use in MRSA or other Gram-positive infections. Telavancin is a semi-synthetic derivative of vancomycin.

<span class="mw-page-title-main">Fleroxacin</span> Chemical compound

Fleroxacin is a quinolone antibiotic. It is sold under the brand names Quinodis and Megalocin.

<span class="mw-page-title-main">Iclaprim</span> Chemical compound

Iclaprim is an antibiotic drug candidate that is active against Gram positive organisms. It is administered intravenously.

mecA is a gene found in bacterial cells which allows them to be resistant to antibiotics such as methicillin, penicillin and other penicillin-like antibiotics.

<span class="mw-page-title-main">Ceftaroline fosamil</span> Chemical compound

Ceftaroline fosamil (INN), brand name Teflaro in the US and Zinforo in Europe, is a cephalosporin antibiotic with anti-MRSA activity. Ceftaroline fosamil is a prodrug of ceftaroline. It is active against methicillin-resistant Staphylococcus aureus (MRSA) and other Gram-positive bacteria. It retains some activity of later-generation cephalosporins having broad-spectrum activity against Gram-negative bacteria, but its effectiveness is relatively much weaker. It is currently being investigated for community-acquired pneumonia and complicated skin and skin structure infection.

<span class="mw-page-title-main">Nemonoxacin</span> Chemical compound

Nemonoxacin is a non-fluorinated quinolone antibiotic undergoing clinical trials. It has the same mechanism of action as fluouroquinolones; it inhibits DNA gyrase, preventing DNA synthesis, gene duplication, and cell division. At the end of 2016, it had reached market in Taiwan, Russia, the Commonwealth Independent States, Turkey, mainland China, and Latin America under the brand name Taigexyn. Nemonoxacin has completed phase 2 trials in the US and has moved on to phase 3 trials. The U.S. Food and Drug Administration (FDA) has granted nemonoxacin qualified infectious disease product (QIDP) and fast track designations for community-acquired bacterial pneumonia (CAP) and acute bacterial skin and skin-structure infections (ABSSSI).

<span class="mw-page-title-main">Omadacycline</span> Chemical compound

Omadacycline, sold under the brand name Nuzyra, is a broad spectrum antibiotic medication belonging to the aminomethylcycline subclass of tetracycline antibiotics. In the United States, it was approved in October 2018, for the treatment of community-acquired bacterial pneumonia and acute skin and skin structure infections.

Kerry L. LaPlante is an American pharmacist, academic and researcher. She is the Dean at the University of Rhode Island College of Pharmacy. She is a Professor of Pharmacy and former department Chair of the Department of Pharmacy Practice at the University of Rhode Island, an adjunct professor of medicine at Brown University, an Infectious Diseases Pharmacotherapy Specialist, and the Director of the Rhode Island Infectious Diseases Fellowship and Research Programs at the Veterans Affairs Medical Center in Providence, Rhode Island.

<span class="mw-page-title-main">Fabimycin</span> Antibiotic

Fabimycin is an newly developed antibiotic candidate which is effective against gram-negative bacterias, an unusually problematic class of bacteria that uses thicker cell walls and molecular efflux pumps to protect themselves by preventing the antibiotics reaching inside the cells.

References

  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.