Preclinical evaluation of MKC-442, a highly potent and specific inhibitor of human immunodeficiency virus type 1 in vitro.
AUTOR(ES)
Baba, M
RESUMO
MKC-442 (6-benzyl-1-ethoxymethyl-5-isopropyluracil or I-EBU) has recently been identified as a highly potent and specific inhibitor of human immunodeficiency virus type 1 (HIV-1) reverse transcriptase. Since the compound has favorable pharmacokinetic and toxicity profiles in vivo, we have evaluated MKC-442 for its inhibitory effect on the replication of HIV-1 in various cell cultures, including human peripheral blood lymphocytes and monocyte-macrophages. The 50 and 90% effective concentrations for HIV-1 (HTLV-IIIB strain) replication in MT-4 cells were 15 and 98 nM, respectively. MKC-442 was also inhibitory to HIV-1 replication in peripheral blood lymphocytes and monocyte-macrophages as determined by the production of p24 antigens in the culture supernatant. Fluorescence-activated cell sorter analysis revealed that MKC-442 was equally active against zidovudine-resistant mutants and zidovudine-susceptible strains. Furthermore, combinations of MKC-442 with either 3'-azido-3'-deoxythymidine, 2',3'-dideoxycytidine, or 2',3'-dideoxyinosine synergistically inhibited the replication of HIV-1. Thus, MKC-442 has been considered as a candidate for clinical efficacy studies.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=284526Documentos Relacionados
- (-)-2'-deoxy-3'-thiacytidine is a potent, highly selective inhibitor of human immunodeficiency virus type 1 and type 2 replication in vitro.
- Preclinical evaluation of HBY 097, a new nonnucleoside reverse transcriptase inhibitor of human immunodeficiency virus type 1 replication.
- U-90152, a potent inhibitor of human immunodeficiency virus type 1 replication.
- Preclinical evaluation of antiviral activity and toxicity of Abbott A77003, an inhibitor of the human immunodeficiency virus type 1 protease.
- ABT-378, a Highly Potent Inhibitor of the Human Immunodeficiency Virus Protease