Preclinical evaluation of MKC-442, a highly potent and specific inhibitor of human immunodeficiency virus type 1 in vitro.


MKC-442 (6-benzyl-1-ethoxymethyl-5-isopropyluracil or I-EBU) has ...
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.




new topics/pols set partial results complete validated


No results available for this paper.

Entry validated by:

Using Polbase tables:


Tables may be sorted by clicking on any of the column titles. A second click reverses the sort order. <Ctrl> + click on the column titles to sort by more than one column (e.g. family then name).


It is also possible to filter the table by typing into the search box above the table. This will instantly hide lines from the table that do not contain your search text.