SC-52151 was a protease inhibitor developed by the company Searle. It was abandoned after it failed to show anti-HIV activity in Phase I studies. SC-52151 is thought to have failed because it binds to a protein in the blood and is then removed from the circulation by the liver. Searle developed a second drug, SC-55389A, which had greater bioavailability, longer half-life and less protein binding than SC-52151, but it too was abandoned.

Key research

Fischl enrolled 48 people with CD4 counts between 150-500 in ACTG 282, a study comparing SC-52151 in the form of an elixir (750 mg three times daily or 1125 mg twice daily) or in the form of a self-emulsifying drug delivery system (SEDDS) at the same doses. There were no significant changes in RNA levels, p24 antigen or CD4 count in any arm.

Arasteh enrolled 101 people with CD4 counts between 50 and 500 and p24 antigen levels greater than 20 pg/ml in a study comparing SC-52151 (250, 500 or 750 mg three times daily) and AZT (200 mg three times daily). SC-52151 had no effect on recipients CD4 counts, p24 antigen levels, plasma RNA or log PBMC titre during 8 weeks therapy.

Sommadossi reported that binding of SC-52151 to the human serum alpha-1 acid glycoprotein (AAG) leads to a major decrease in intracellular drug uptake. 1.25 mg/ml AAG, a level well below that seen in people with AIDS, resulted in a greater than 85% inhibition of the intracellular uptake of SC-52151, increasing the IC₉₀ by 35-40-fold. Similar effects were observed with SC-55389A.

References

Arast騠K et al. Proteinase inhibitor (SC-52 151, Searle) vs AZT a Phase II study to evaluate the pharmacokinetic and efficacy of SC-52 151. Fifth International Conference on Clinical Aspects and Treatment of HIV Infection, Copenhagan, abstract 44, 1995.

Bryant M et al. The HIV protease inhibitor SC-5215 (sic). First National Conference on Human Retroviruses, Washington, abstract 261, 1993.

Fischl MA et al. Phase I study of two formulations and dose schedules of SC-52151, a protease inhibitor. Second National Conference on Human Retroviruses, Washington, abstract 186, 1995.

Sommadossi J-P et al. A human serum glycoprotein profoundly affects antiviral activity of the protease inhibitor SC-52151 by decreasing its cellular uptake. Second National Conference on Human Retroviruses, Washington, abstract LB4, 1995.