Fostemsavir

from Wikipedia, the free encyclopedia
Structural formula
Structure of fostemsavir
General
Non-proprietary name Fostemsavir
other names
  • {3 - [(4-Benzoylpiperazin-1-yl) oxoacetyl] -4-methoxy-7- (3-methyl-1 H -1,2,4-triazol-1-yl) -1 H -pyrrolo [2nd , 3-c] pyridin-1-yl} methyl dihydrogen phosphate
  • BMS-663068
Molecular formula C 25 H 26 N 7 O 8 P
External identifiers / databases
CAS number
  • 864953-29-7
  • 864953-39-9 (fostemsavir- trometamol )
PubChem 11319217
ChemSpider 9494181
DrugBank DB11796
Wikidata Q17001240
Drug information
Drug class

Antiviral

properties
Molar mass 583.49 g mol −1
safety instructions
GHS hazard labeling
no classification available
As far as possible and customary, SI units are used. Unless otherwise noted, the data given apply to standard conditions .

Fostemsavir is a virostatic effective drug . It was approved under the name Rukobia ( Marketing Authorization Holder : ViiV Healthcare ) in the United States in 2020 for the oral treatment of HIV infections .

background

An HIV infection is now considered to be an easily treatable, manageable, lifelong disease. However, about 6% of adults living with HIV have little or no possibility of treatment for the HIV infection due to resistance, tolerance or safety considerations . These people have previously been at risk of developing AIDS and premature death. This drug could potentially restore some of these people to normal lives.

indication

The HIV drug should be used in combination with other antiretroviral drugs to treat adults with multidrug-resistant HIV-1 infection , if no suppressive antiviral treatment regimen is available due to resistance, intolerance or safety considerations.

Side effects

The most common side effects that were seen in at least 5% of the study participants were:

  • nausea
  • fatigue
  • diarrhea

3% of people taking fostemsavir had serious drug reactions, including three cases of severe immune reconstitution inflammatory syndrome (IRIS), a severe immune system reaction.

Mechanism of action

Temsavir (BMS-626529)

Fostemsavir is the prodrug of temsavir . The pharmacologically active form is created by hydrolysis. Temsavir blocked the gp120 , a specific receptor on the surface of the virus, so that the initial viral binding to CD4 + T-cell host is prevented. This prevents entry into the host's immune cell. The drug attacks another step in the life cycle of the virus, so that the active ingredient has potential in the treatment of resistant HI viruses.

development

Based on the structure indole-3-gyloxamide , which was identified in a high-throughput screening , which interferes with the HIV-1 entry process , targeted optimization of the molecule led to the attachment inhibitor temsavir. Its phosphonooxymethyl derivative fostemsavir was developed to improve absorption properties and the resulting bioavailability . Development history and synthesis are described in the literature. The active ingredient is used pharmaceutically as fostemsavir trometamol.

The approval of Rukobia in the USA is based on the results of the BRIGHTE study, which was carried out over 96 weeks in 371 treatment-experienced subjects with HIV-1 resistance. Patients with a viral load of> 400 copies / ml and failure to treat various antiretroviral drug classes due to resistance, intolerance, contraindication or other safety concerns were included (a maximum of 2 classes of antiretroviral drugs remaining at the start of the study).

Fostemsavir is currently being reviewed by the European Medicines Agency . Further filings with regulators around the world are planned for 2020 and 2021.

Individual evidence

  1. ↑ This substance has either not yet been classified with regard to its hazardousness or a reliable and citable source has not yet been found.
  2. ↑ Novel Drug Approvals for 2020 . FDA .
  3. ↑ a b ViiV Healthcare announces US FDA approval for Rukobia (fostemsavir), a first-in-class treatment for HIV in adults with few treatment options available. July 2, 2020, accessed on July 25, 2020 .
  4. ↑ fostemsavir. On the website of HIV & more online. January 30, 2020, accessed July 25, 2020 .
  5. ↑ a b Rukobia - fostemsavir tromethamine tablet, film coated, extended release . DailyMed .
  6. ↑ A. Negt: ViiV : Fostemsavir approval application submitted. Pharmacy adhoc. January 30, 2020, accessed on July 25, 2020 (German).
  7. ^ NA Meanwell et al .: Inhibitors of HIV-1 Attachment: The Discovery and Development of Temsavir and its Prodrug Fostemsavir . In: Journal of Medicinal Chemistry . tape 61 , 2018, p. 62-80 , doi : 10.1021 / acs.jmedchem.7b01337 .
  8. ↑ External identifiers or database links for fostemsavir-trometamol : CAS number: 864953-39-9, EC number: 682-137-1, ECHA InfoCard: 100.207.286 , PubChem : 46892186 , ChemSpider : 28637754 , Wikidata : Q27255740 . {3 - [(4-Benzoylpiperazin-1-yl) oxoacetyl] -4-methoxy-7- (3-methyl-1 H -1,2,4-triazol-1-yl) -1 H -pyrrolo [2nd , 3-c] pyridin-1-yl} methyl dihydrogen phosphate 2-amino-2- (hydroxymethyl) propane-1,3-diol salt (1: 1). C 25 H 26 N 7 O 8 P C 4 H 11 NO 3 , molar mass: 704.6 g mol −1 . Codes: BMS-663068-03, GSK3684934A