KNI-272 is the codename for a protease inhibitor formerly being developed by Agouron . It is also known as kynostatin. The drug was originally developed by the Japan Energy Corporation.

KNI-272 demonstrated anti-viral activity against a wide range of HIV-1 strains and HIV-2, but trials reportedly suggested that it was less active than ritonavir or indinavir, had unfavourable pharmacokinetics and its activity was blocked by the same resistance mutations.

Research to date has found that 40 mg per kilogram of body weight daily is the most promising dose. The drug is taken four times a day.

Its development was abandoned in 1996.

Key research

Humphrey enrolled 37 people with AIDS or symptomatic HIV disease into a phase I study of KNI-272. A daily dose of 40mg per kg was found to be most effective dose. Higher doses were associated with significant liver toxicity. Slight anti-HIV effect was sustained at 78 weeks of treatment and there was a trend towards higher CD4 counts.

References

Anderson B et al. In vitro induction of HIV-1 with reduced sensitivity to HIV protease inhibitors, KNI-227 and KNI-272. Second National Conference on Human Retroviruses and Related Infections, Washington, abstract 95, 1995.

Humphrey RW et al. A phase I trial of the pharmacokinetics, toxicity, and activity of KNI-272, an inhibitor of HIV-1 protease, in patients with AIDS or symptomatic HIV infection. Antiviral Research 41(1):21-33, 1999.

Tanaka M et al. Identification of protease inhibitors containing allophenylnorstatine active against both wild-type and KNI-272-resistant HIV-1 variants. Eleventh International Conference on AIDS, Vancouver, abstract Tu.A.260, 1996.