Elvucitabine

  • β -L- 2 ', 3' -dideoxy- 2 ', 3'- didehydro -5- fluorocytidine ( β -L- Fd4C )
  • 4-amino -5-fluoro -1-[ (2S, 5R) - 5 - ( hydroxymethyl) -2,5- dihydro-furan- 2-yl ] pyrimidin- 2-one ( IUPAC)
  • Elvucitabinum (Latin )
  • ACH -126, 443 ( Achillion )

Antiviral agent, nucleoside reverse transcriptase inhibitors

Competitive inhibition of reverse transcriptase

Template: Infobox chemical / molecular formula search available

Elvucitabin (ACH -126, 443 ) is an experimental drug for the treatment of HIV and its subsequent stages in a combination therapy for HIV and HBV infection.

He is a cytidine analog and belongs to the group of nukelosidischen reverse transcriptase - inhibitors ( NRTIs).

History

Elvucitabin is being developed by Achillion Pharmaceuticals. Another Sudie patients with lamivudine ( Epivir) or emtricitabine ( Emtriva ) resistance and simultaneous M184 mutation was completed in 2007. The results are expected in early 2008.

Pharmacology

Elvucitabin is an enantiomer of Dexelvucitabin ( Reverset ) and also has activity against HIV and HBV. Currently running phase II trials in HIV and HBV. In HIV-infected patients with the M184V mutation was found in a small, double-blind study, a decrease in viral load by 0.7-0.8 logs after 28 days. The study, however, was canceled because below 100 mg elvucitabine in 6/ 56 patients developed leucopenia occurred.

Make comparative studies with Epivir suggest that the suppressive effect of Elvucitabin is slightly weaker ( average 0.3 logs ).

Mitochondrial toxicity seems less than under Dexelvucitabine. Current results show that possibly the binding affinity for reverse transcriptase resistant virus is less.

Pharmacokinetics

Studies in an extremely long half-life of 150 hours was determined. Against this background, a once -daily dosing seems very likely.

Side effects

Positive fell in studies on the apparently low mitochondrial toxicity. However, a study had to be terminated because below 100 mg elvucitabine in 6/ 56 patients developed leucopenia occurred. Some patients also developed rashes. Pancreatitis as under Dexelvucitabine other hand, seem not to occur.

Resistance

In vitro showed a good activity against various NRTI resistance. There the selection of virus with its own resistance as M184I or the previously quite unknown mutant D237E was observed. Probably the selection of this particular resistance among HAART will not be watching.

CAS registry number PubChem Active ingredient Structural analog Leukopenia Antiviral Research
305377
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