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Entecavir

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Entecavir
File:Entecavir structure.png
Clinical data
License data
Routes of
administration		Oral
ATC code
Legal status
Legal status
Pharmacokinetic data
Protein binding13%
Elimination half-life128–149 hours
ExcretionRenal 62–73%
Identifiers
  • 2-Amino-9-[(1S,3R,4S)-4-hydroxy-3-(hydroxymethyl)-2-methylidenecyclopentyl]-6,9-dihydro-3H-purin-6-one
CAS Number
PubChem CID
DrugBank
ChemSpider
UNII
CompTox Dashboard (EPA)
ECHA InfoCard100.111.234 Edit this at Wikidata
Chemical and physical data
FormulaC12H15N5O3
Molar mass277.279 g/mol g·mol−1
3D model (JSmol)
  • O.C=C3[C@H](CO)[C@@H](O)C[C@@H]3n2cnc1c2\N=C(\N)NC1=O
  • InChI=1S/C12H15N5O3.H2O/c1-5-6(3-18)8(19)2-7(5)17-4-14-9-10(17)15-12(13)16-11(9)20;/h4,6-8,18-19H,1-3H2,(H3,13,15,16,20);1H2/t6-,7-,8-;/m0./s1 checkY
  • Key:YXPVEXCTPGULBZ-WQYNNSOESA-N checkY
  (verify)

Entecavir(abbr. ETV) (INN) (Template:Pron-en) is an oral antiviral drug used in the treatment of hepatitis B infection. It is marketed under the trade name Baraclude (BMS).

Entecavir is a nucleoside analog[2] (more specifically, a guanine analogue) that inhibits reverse transcription, DNA replication and transcription in the viral replication process. The drug's manufacturer claims that entecavir is more efficacious than previous agents used to treat hepatitis B (lamivudine and adefovir).

Entecavir was approved by the U.S.FDA in March 2005.

USES Entecavir is used to treat chronic hepatitis B. It also helps prevent the hepatitis B virus from multiplying and infecting new liver cells. Entecavir is also indicated for the treatment of chronic hepatitis B in adults with HIV/AIDS infection. However, entecavir is not active against HIV.

Clinical Trials

The clinical efficacy of entecavir has been studied in several randomized, double-blind, multicentre trials. Oral entecavir was an effective and generally well tolerated treatment.[3]

History

  • 1992: SQ-34676 at Squibb as part of anti-herpes virus program[4]
  • 1997: BMS 200475 developed at BMS pharmaceutical research institute as antiviral nucleoside analogue à Activity demonstrated against HBV, HSV-1, HCMV, VZV in cell lines & no or little activity against HIV or influenza[5]
  • Superior activity observed against HBV pushed research towards BMS 200475, its base analogues and its enantiomer against HBV in HepG2.2.15 cell line[5]
  • Comparison to other NAs, proven more selective potent inhibitor of HBV by virtue of being Guanine NA[6]
  • 1998: Inhibition of hepadnaviral polymerases was demonstrated in vitro in comparison to a number of NAs-TP[7]
  • Metabolic studies showed more efficient phosphorylation to triphosphate active form[8]
  • 3 year treatment of woodchuck model of CHB à sustained antiviral efficacy and prolonged life spans without detectable emergence of resistance[9]
  • Efficacy # LVD resistant HBV replication in vitro[10]
  • Superior activity compared to LVD invivo for both HBeAg + & HBeAg- patients[11][12]
  • Efficacy in LVD refractory CHB patients[13]

References

  1. ^ "FDA-sourced list of all drugs with black box warnings (Use Download Full Results and View Query links.)". nctr-crs.fda.gov. FDA. Retrieved 22 Oct 2023.
  2. ^ Sims KA, Woodland AM (2006). "Entecavir: a new nucleoside analog for the treatment of chronic hepatitis B infection". Pharmacotherapy. 26 (12): 1745–57. doi:10.1592/phco.26.12.1745. PMID 17125436. {{cite journal}}: Unknown parameter |month= ignored (help)
  3. ^ Scott LJ, Keating GM.[1].Drugs 2009;69(8):1003-1033. doi: 10.2165/00003495-200969080-00005.
  4. ^ Slusarchyk, W. A., A. K. Field, J. A. Greytok, P. Taunk, A. V. Tooumari, M. G. Young, and R. Zahler. 4-Hydroxy-3-(hydroxymethyl)-2-methylcyclopentyl purines and pyrimidines, a novel class of anti-herpesvirus agents. Abstract from the Fifth International Conference on Antiviral Research. Antivir Res 1992.17(Suppl. 1):98
  5. ^ a b Bisacchi, G. S., S. T. Chao, C. Bachard, J. P. Daris, S. F. Innaimo, J. A. Jacobs, O. Kocy, P. Lapointe, A. Martel, Z. Merchant, W. A. Slusarchyk, J. E. Sundeen, M. G. Young, R. Colonno, and R. Zahler. BMS-200475, a novel carbocyclic 29-deoxyguanosine analog with potent and selective antihepatitis B virus activity in vitro. Bioorg. Med. Chem. Lett. 1997. 7:127–132
  6. ^ Innaimo S F, Seifer M, Bisacchi G S, Standring D N, Zahler R, Colonno R J. Identification of BMS-200475 as a Potent and Selective Inhibitor of Hepatitis B Virus. Antimicrob. Agents Chemother. 1997. 41(7): 1444–1448
  7. ^ Seifer, M., R. K. Hamatake, R. J. Colonno, and D. N. Standring. In vitro inhibition of hepadnavirus polymerases by the triphosphates of BMS-200475 and lobucavir. Antimicrob. Agents Chemother. 1998. 42:3200–3208
  8. ^ Yamanaka, G., T. Wilson, S. Innaimo, G. S. Bisacchi, P. Egli, J. K. Rinehart, R. Zahler, and R. J. Colonno. Metabolic studies on BMS-200475, a new antiviral compound active against hepatitis B virus. Antimicrob. Agents Chemother. 1999. 43:190–193
  9. ^ Colonno, R. J., E. V. Genovesi, I. Medina, L. Lamb, S. K. Durham, M. L. Huang, L. Corey, M. Littlejohn, S. Locarnini, B. C. Tennant, B. Rose, and J. M. Clark. Long-term entecavir treatment results in sustained antiviral efficacy and prolonged life span in the woodchuck model of chronic hepatitis infection. J. Infect. Dis. 2001.184:1236–1245
  10. ^ Levine, S., D. Hernandez, G. Yamanaka, S. Zhang, R. Rose, S. Weinheimer, and R. J. Colonno. Efficacies of entecavir against lamivudine-resistant hepatitis B virus replication and recombinant polymerases in vitro. Antimicrob. Agents Chemother. 2002.46:2525–2532
  11. ^ Chang, T. T. A comparison of entecavir and lamivudine for HBeAg-positive chronic hepatitis B. N. Engl. J. Med. 2006. 354:1001–1010
  12. ^ Lai, C. L. et al. Entecavir versus lamivudine for patients with HBeAg-negative chronic hepatitis B. N. Engl. J.Med. 2006. 354:1011–1020.
  13. ^ Sherman, M., C. Yurdaydin, J. Sollano, M. Silva, Y. F. Liaw, J. Cianciara, A. Boron-Kaczmarska, P. Martin, Z. Goodman, R. J. Colonno, A. Cross, G. Denisky, B. Kreter, R. Hindes, and the AI463026 Behold Study Group. Entecavir for the treatment of lamivudine-refractory, HBeAg-positive chronic hepatitis B. Gastroenterology 2006. 130:2039–2049.
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