Betulinic acid (ALS-357) is a pentacyclic lupane-type triterpene derivative of betulin (isolated from the bark of Betula alba, the common white birch) which has antiretroviral, antimalarial, and anti-inflammatory properties, as well as a more recently discovered potential as an anticancer agent, by inhibition of topoisomerase.

Aminopeptidase N:7.3 μM, Topo I (eukaryotic):5 μM, HIV-1:1.4 μM(EC50)

In LNCaP cell cultures of athymic nude mice, Betulinic acid inhibits the growth of prostate cancer cells and tumors (xenografts). This inhibitory effect is partly due to the downregulation of protease-dependent Sp1/3/4 and several SP-regulated genes.

As an anti-melanoma agent, Betulinic acid inhibits the activity of aminopeptidase N (IC50: 7.3 μM). It exhibits anti-HIV properties by blocking HIV replication in H9 lymphocytes (EC50: 1.4 μM) and inhibiting the growth of uninfected H9 cells (IC50: 13 μM). Moreover, Betulinic acid shows potential as an anti-cancer candidate, suppressing the activity of eukaryotic topoisomerase I (IC50: 5 μM).

Topoisomerase I-DNA interaction: Annealed 25-mer duplex of oligonucleotide-1 and oligonicleotide-2 is incubated with 25 or 50 units of rat liver topoisomerase I at 8 °C for 15 min in the presence or absence of betulinic acid in binding buffer. After incubation the reaction mixtures are electrophoresed in 7% non-denaturing polyacrylamide gel at 4 °C in 0.167 × TBE buffer and DNA bands are stained with ethidium bromid