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DPC-083. DuPont Pharmaceuticals.

¹University of California at San Francisco, Department of Clinical Pharmacy, 521 Pamassus Avenue, C-152, Box 0622, San Francisco, CA 94143-0622, USA. michaelleelim@hotmail.com

Current Opinion in Investigational Drugs (London, England : 2000)

|November 23, 2001

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DuPont Pharmaceuticals is developing DPC-083 and DPC-961, non-nucleoside reverse transcriptase inhibitors (NNRTIs), for HIV treatment. These drugs show antiviral activity against resistant HIV-1 variants, including the K103N mutant.

Area of Science:

Pharmacology
Virology
Medicinal Chemistry

Background:

Human Immunodeficiency Virus (HIV) infection remains a significant global health challenge.
Development of novel antiviral agents is crucial to combat drug resistance and improve treatment outcomes.
Non-nucleoside reverse transcriptase inhibitors (NNRTIs) are a key class of antiretroviral drugs.

Purpose of the Study:

To evaluate the potential of DPC-083 and DPC-961 as novel treatments for HIV infection.
To assess the antiviral activity of these compounds against wild-type and mutant HIV-1 strains.
To explore the development of novel tricyclic quinazolinones with biological activity.

Main Methods:

Clinical trials (Phase I, II, and III) were conducted to assess safety and efficacy.

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Antiviral activity was tested against various HIV-1 variants, including the K103N mutant.

Pharmacological studies in rhesus monkeys were performed to compare potency with existing drugs.

Main Results:

DPC-083 and DPC-961 demonstrated antiviral activity against mutant HIV-1 variants, including K103N.
The compounds exhibited comparable potency to efavirenz against wild-type virus in preclinical models.
Phase I trials were completed, with DPC-083 progressing to Phase II trials for combination therapy.

Conclusions:

DPC-083 and DPC-961 represent promising candidates for HIV treatment, particularly against resistant strains.
Further clinical development is underway, with anticipated NDA filing in 2003.
The investigation also identified novel tricyclic quinazolinones with potential biological significance.