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 Clostridium 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 round-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 that can grow without the need for 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) 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 attributable to antimicrobial resistance in 2019.

Linezolid 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.

Clindamycin Antibiotic used for treatment of bacterial infections

Clindamycin is an 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.

Fusidic acid Antibiotic

Fusidic acid, sold under the brand names Busid among others, is an antibiotic that is often used topically in creams and eyedrops but may also be given systemically as tablets or injections. The global problem of advancing antimicrobial resistance has led to a renewed interest in its use recently.

Metelimumab (CAT-192) is a human IgG4 monoclonal antibody that neutralizes TGF beta 1 which had been chosen for further development for the treatment of diffuse cutaneous systemic sclerosis, also known as scleroderma. It was dropped from further development in favour of fresolimumab, which was being developed by Genzyme as of 2006.

Tefibazumab is a humanized monoclonal antibody for the treatment of severe infections with Staphylococcus aureus. Possible indications include the treatment of S. aureus in a phase 2a patients with cystic fibrosis and of methicillin-resistant S. aureus.

Oritavancin

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.

Cefoxitin

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.

Basilea Pharmaceutica

Basilea Pharmaceutica is a multinational specialty biopharmaceutical company headquartered in Basel, Switzerland. It was formed as a spin-off entity from the drug giant Hoffmann–La Roche in October 2000. It is engaged in the development of antibiotics, antifungals and oncology drugs for treatment of invasive aspergillosis and invasive mucormycosis. Basilea is publicly traded on the SIX Swiss exchange.

Dalbavancin

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).

Telavancin

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

Nadifloxacin

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

Iclaprim

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

Ceftaroline fosamil

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.

Linopristin/flopristin is an experimental drug candidate under development by Novexel. It is an oral streptogramin antibiotic that has potent in vitro activity against certain Gram-positive bacteria including methicillin resistant Staphylococcus aureus (MRSA), as well as the important respiratory pathogens including penicillin-, macrolide- and quinolone-resistant strains. It is a combination of linopristin and flopristin.

Taksta is a front-loaded oral dosing regimen of sodium fusidate under development in the U.S. as an antibiotic for gram-positive infections including drug-resistant strains such as methicillin-resistant Staphylococcus aureus (MRSA).

Brilacidin, an investigational new drug (IND), is a polymer-based antibiotic currently in human clinical trials, and represents a new class of antibiotics called host defense protein mimetics, or HDP-mimetics, which are non-peptide synthetic small molecules modeled after host defense peptides (HDPs). HDPs, also called antimicrobial peptides, some of which are defensins, are part of the innate immune response and are common to most higher forms of life. As brilacidin is modeled after a defensin, it is also called a defensin mimetic.

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.

Lonapegsomatropin, sold under the brand name Skytrofa, is a human growth hormone used for the treatment of growth hormone deficiency. Lonapegsomatropin is a prodrug of somatropin.

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.
  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