XF-73

Last updated

XF-73
XF 73.svg
Identifiers
3D model (JSmol)
ChemSpider
PubChem CID
UNII
  • InChI=1S/C44H50N6O2.2ClH/c1-49(2,3)25-7-27-51-37-17-9-31(10-18-37)43-39-21-13-33(45-39)29-35-15-23-41(47-35)44(42-24-16-36(48-42)30-34-14-22-40(43)46-34)32-11-19-38(20-12-32)52-28-8-26-50(4,5)6;;/h9-24,29-30,45-46H,7-8,25-28H2,1-6H3;2*1H/q+2;;/p-2/b33-29-,34-30-,35-29-,36-30-,43-39-,43-40-,44-41-,44-42-;;
    Key: BXHQXSXRVAELBC-XRFOENPRSA-L
  • InChI=1/C44H50N6O2.2ClH/c1-49(2,3)25-7-27-51-37-17-9-31(10-18-37)43-39-21-13-33(45-39)29-35-15-23-41(47-35)44(42-24-16-36(48-42)30-34-14-22-40(43)46-34)32-11-19-38(20-12-32)52-28-8-26-50(4,5)6;;/h9-24,29-30,45-46H,7-8,25-28H2,1-6H3;2*1H/q+2;;/p-2/b33-29-,34-30-,35-29-,36-30-,43-39-,43-40-,44-41-,44-42-;;
    Key: BXHQXSXRVAELBC-NDLTUMITBE
  • C[N+](C)(C)CCCOC(C=C1)=CC=C1/C(C2=CC=C(/C=C3C=CC(/C(C4=CC=C(OCCC[N+](C)(C)C)C=C4)=C(N/5)/C=CC5=C\6)=N/3)N2)=C7N=C6C=C/7.[Cl-].[Cl-]
Properties
C44H50Cl2N6O2
Molar mass 765.82 g·mol−1
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).

XF-73 (Exeporfinium chloride) is an experimental drug candidate. It is an anti-microbial that works via weakening bacteria cell walls. [1] It is a potential treatment for methicillin-resistant Staphylococcus aureus (MRSA) and possibly Clostridioides difficile . It is being developed by Destiny Pharma Ltd. [2] [3] [4]

Structurally, it is a dicationic porphyrin. [5]

It has completed a phase I clinical trial for nasal decolonisation of MRSA—being tested against 5 bacterial strains. It seems unlikely to cause MRSA to develop resistance to it. [1] [6]

In 2014, a phase 1 clinical trial for nasal administration was run. [7]

As of June 2022, another phase 1 clinical trial (for nasal administration) completed recruiting in 2016 but no results have been posted. [8]

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.

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.

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

Clindamycin is a lincosamide antibiotic medication used for the treatment of a number of bacterial infections, including osteomyelitis (bone) or joint infections, pelvic inflammatory disease, strep throat, pneumonia, acute otitis media, and endocarditis. It can also be used to treat acne, and some cases of methicillin-resistant Staphylococcus aureus (MRSA). In combination with quinine, it can be used to treat malaria. It is available by mouth, by injection into a vein, and as a cream or a gel to be applied to the skin or in the vagina.

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

Fusidic acid, sold under the brand name Fucidin among others, is a steroid antibiotic that is often used topically in creams or ointments and eyedrops but may also be given systemically as tablets or injections. As of October 2008, the global problem of advancing antimicrobial resistance has led to a renewed interest in its use.

<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.

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

Cefoxitin is a second-generation cephamycin antibiotic developed by Merck & Co., Inc. from Cephamycin C in the year following its discovery, 1972. It was synthesized in order to create an antibiotic with a broader spectrum. It is often grouped with the second-generation cephalosporins. Cefoxitin requires a prescription and as of 2010 is sold under the brand name Mefoxin by Bioniche Pharma, LLC. The generic version of cefoxitin is known as cefoxitin sodium.

<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">Dalbavancin</span> Antibiotic used to treat MRSA

Dalbavancin, sold under the brand names Dalvance in the US and Xydalba in the EU among others, is a second-generation lipoglycopeptide antibiotic medication. It belongs to the same class as vancomycin, the most widely used and one of the treatments available to people infected with methicillin-resistant Staphylococcus aureus (MRSA).

<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">Nadifloxacin</span> Chemical compound

Nadifloxacin is a topical fluoroquinolone antibiotic for the treatment of acne vulgaris. It is also used to treat bacterial skin infections.

<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.

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

Delafloxacin sold under the brand name Baxdela among others, is a fluoroquinolone antibiotic used to treat acute bacterial skin and skin structure infections.

<span class="mw-page-title-main">Tedizolid</span> Oxazolidinone-class antibiotic

Tedizolid, sold under the brand name Sivextro is an oxazolidinone-class antibiotic. Tedizolid phosphate is a phosphate ester prodrug of the active compound tedizolid. It was developed by Cubist Pharmaceuticals, following acquisition of Trius Therapeutics, and is marketed for the treatment of acute bacterial skin and skin structure infections.

<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">Lipoglycopeptide</span> Class of chemical compounds

Lipoglycopeptides are a class of antibiotic that have lipophilic side-chains linked to glycopeptides. The class includes oritavancin, telavancin and dalbavancin.

<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).

CC398 or MRSA CC398 is a new variant of MRSA that has emerged in animals and is found in intensively reared production animals, where it can be transmitted to humans as LA-MRSA. A 2009 study shows, however, that dissemination of CC398 from exposed humans to other, non-exposed humans is infrequent. Though dangerous to humans, CC398 is often asymptomatic in food-producing animals. In a single study conducted in Denmark, MRSA was shown to originate in livestock and spread to humans, though the MRSA strain may have originated in humans and was transmitted to livestock.

Decolonization, also bacterial decolonization, is a medical intervention that attempts to rid a patient of an antimicrobial resistant pathogen, such as methicillin-resistant Staphylococcus aureus (MRSA) or antifungal-resistant Candida.

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

Contezolid is an antibiotic of the oxazolidinone class. It is effective against Staphylococcus aureus, methicillin-resistant Staphylococcus aureus (MRSA), Streptococcus pyogenes, Streptococcus agalactiae, and other bacteria.

References

  1. 1 2 Neka Sehgal (20 September 2010). "Promising new drug XF-73 kills superbugs within 5 minutes". Archived from the original on 21 July 2011.
  2. "XF-73". Destiny Pharma. 29 July 2016. (Shows molecular structure.)
  3. Miller, K.; Ooi, N.; Hobbs, J. K.; Rhys-Williams, W.; Love, W. G.; Hayter, I.; Katila, M.; Chopra, I. (19 April 2008). "XF-73, a novel anti-staphylococcal antimicrobial with very rapid bactericidal activity". European Society of Clinical Microbiology and Infectious Diseases.{{cite journal}}: Cite journal requires |journal= (help)
  4. Mary Dejevsky (18 May 2008). "Scientists 'on brink of cure' for superbug" . The Independent. Archived from the original on 7 May 2022.
  5. "XF series". Destiny Pharma. 29 July 2016.
  6. Tom Chivers (18 May 2008). "MRSA: UK scientists 'close to a treatment". The Daily Telegraph . Archived from the original on 21 April 2013.
  7. Study of the Nasal Decolonisation of Staphylococcus Aureus (SA) and the Safety and Tolerability of XF-73 Nasal Gel in Healthy Subjects
  8. Study of the Safety and Local Tolerability of Intranasal Gel Formulations of XF-73