Alpha-APA: New Anti-HIV Compound

A drug code-named R89439, one of a class of chemicals called
alpha-anilino phenyl acetamides (alpha-APA), has been discovered
as a highly specific anti-HIV-1 agent at the Riga Institute for
Medical Research in Leuven, Belgium, in collaboration with the
Janssen Research Foundation in Beerse, Belgium. It has been
presented at three scientific meetings so far, including the VIII
International Conference on AIDS in Amsterdam. This potential
treatment is interesting for several reasons:

* In laboratory tests it is effective against HIV-1 at
very small concentrations, a few nanograms per ml. It also
has an unusually large ratio (about 1 to 50,000) between the
concentration effective against HIV and that which is toxic
to cells.

* R89439 has been through standard animal toxicity
tests and has been tested in people, in a few HIV-negative
volunteers. It is orally available and will probably need to
be taken only once or twice a day; eight hours after taking
a single 100 mg dose, blood levels in humans are 30 times
the amount needed to inhibit HIV. No particular toxicity is
expected, although toxicity cannot be ruled out. Laboratory
tests suggest that the drug is synergistic when combined
with AZT or with ddI.

* Some alpha-APA derivatives are relatively easy to
manufacture, and could be available in any country in the
world.

The alpha-APA derivatives act by inhibiting reverse
transcriptase and are very specific to HIV-1, which suggests that
resistance may develop to this class of compounds, as it has with
other drugs that are specifically targeted at the HIV-1 reverse
transcriptase. At this time, however, no one knows how serious
any resistance problem might be.

Alpha-APA (R89439) will next be tested in phase I/II trials
in several European countries.

(AIDS TREATMENT NEWS article includes structural formula of
R89439 here.)

References

Pauwels R, Andries K, Debyser Z, Van Daele P, Schols D, Janssen
MAC, Desmyter J, De Clercq E, and Janssen PAJ. HIV-1 specific
phenylacetamide derivatives: A novel class of reverse
transcriptase inhibitors with potent and selective antiviral
activity in vitro. Fifth International Conference on Antiviral
Research, Vancouver, March 8-13, 1992; abstract published in
Antiviral Research, Supplement 1, March 1992 [abstract #5, page
45].

Pauwels R, Andries K, Schols D, Van Daele P, Debyset Z, Janssen
MAC, Vandamme A, De Vreese K, Desmyter J, De Clercq E, and
Janssen PAJ. Potent and highly selective HIV-1 specific
inhibition by a new series of alpha-anilino phenylacetamide
(alpha-APA) derivatives targeted at HIV-1 RT. VIII International
Conference on AIDS, Amsterdam, June 19-24, 1992 [abstract # PoA
2320].

Janssen PAJ, Stoffels P, Andries K, Van Daele P, Woestenborghs R,
Pauwels R, Heykants J, Mesens J, Cauwenbergh G, Desmyter J, De
Clercq E, and Janssen MAC. Inhibition of HIV-1 by a new series
of alpha-anilino phenyl acetamide (alpha-APA) derivatives. VIII
International Conference on AIDS, Amsterdam, June 19-24, 1992
[abstract # PoB 3020].