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T20; Pentafuside; Enfuvirtide; Fuzeon; Dp 178; Dp178; HSDB 7341; HSDB7341; T-20; T 20
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Enfuvirtide (INN) is an HIV fusion inhibitor, the first of a novel class of antiretroviral drugs used in combination therapy for the treatment of HIV-1 infection.
Enfuvirtide is a 36 amino acid peptide corresponding to a region of gp41, the transmembrane subunit of HIV-1 envelope protein. It belongs to the therapeutic class of fusion inhibitors and acts by binding to gp41 and impeding the conformational changes in gp41 necessary for fusion of the virus with the cell.
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Antiretroviral drugs

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Enfuvirtide is a short polypeptide with activity against human immunodeficiency virus (HIV). Enfuvirtide binds to the first heptad-repeat (HR1) in the gp41 viral envelope glycoprotein, thereby preventing conformational changes required for fusion of viral and cellular membranes and preventing the virus from entering a host cell. Enfuvirtide is the first of a new class of agents active against the human immunodeficiency virus (HIV). Enfuvirtide has not been associated with serum aminotransferase elevations during therapy or episodes of acute, clinically apparent liver injury.

Enfuvirtide is the first fusion inhibitor to be approved by the Food and Drug Administration for the treatment of chronic human immunodeficiency virus (HIV) infection in adults and children 6 years and older. The drug is a synthetic peptide derived from a naturally occurring amino acid sequence known as heptad repeat 2 (HR2) found in gp41, a viral transmembrane glycoprotein that facilitates fusion with host cells. By mimicking the activity of HR2 and competitively binding to a second region of gp41, heptad repeat 1 (HR1), enfuvirtide prevents interaction between HR1 and HR2 and inhibits the conformational change of gp41 that is necessary for fusion of virions to host cells. The safety and efficacy of enfuvirtide have been studied only in antiretroviral-experienced persons.

Hardy, H., & Skolnik, P. R. (2004). Enfuvirtide, a new fusion inhibitor for therapy of human immunodeficiency virus infection. Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy, 24(2), 198-211.

Drug resistance continues to be a major challenge in the treatment of HIV-1 infection. Virtually all currently available antiretroviral medications inhibit the viral reverse transcriptase or protease. Enfuvirtide is the first fusion inhibitor approved by the US Food and Drug Administration for use in combination with other antiretroviral agents for the treatment of HIV-1 infection in treatment-experienced patients.

Fung, H. B., & Guo, Y. (2004). Enfuvirtide: a fusion inhibitor for the treatment of HIV infection. Clinical therapeutics, 26(3), 352-378.

The increasing prevalence of HIV isolates resistant to one or multiple antiretroviral drugs has fueled the search for new agents that work by novel mechanisms. Enfuvirtide (ENF), licensed in 2002, is the first marketed antiretroviral (ARV) agent that targets viral entry. ENF blocks the virus replication cycle by binding to gp41, a critical component of the machinery used by HIV to enter host cells. As with all ARVs, HIV can evolve resistance to ENF. However, resistance to ENF appears to be somewhat more complex and can derive through either direct or indirect pathways. Direct resistance occurs when mutations in the first heptad repeat of gp41, which constitutes the ENF-binding site, reduce ENF binding.

Miller, M. D., & Hazuda, D. J. (2004). HIV resistance to the fusion inhibitor enfuvirtide: mechanisms and clinical implications. Drug resistance updates, 7(2), 89-95.

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