In murine models of L1210 leukemia, a single intravenous dose of PNU-159682 at 15 μg/kg was identified as the maximum tolerated dose, resulting in a 29% increase in lifespan—a figure closely rivaling the effect of a significantly higher dose of MMDX (90 μg/kg) which led to a 36% increase. This comparison highlights PNU-159682's potent antitumor activity at lower doses^[1].

Further, in MX-1 human mammary carcinoma mice models, PNU-159682 administered intravenously at 4 μg/kg on a schedule of every 7 days for three cycles (q7dx3) over 40 days elicited a strong therapeutic response. Remarkably, starting from day 39, four out of seven mice treated with PNU-159682 showed complete tumor regression, underscoring its potent efficacy against solid tumors^[1].

PNU-159682's application extends beyond individual treatment to enhancing ADCs. When conjugated to the anti-CD22 antibody (anti-CD22-NMS249), it demonstrates strong anti-tumor effects in vivo, with an ADC dose (50 μg/m2 of conjugated PNU-159682) being well tolerated in mice and causing less than 10% weight loss. This suggests that PNU-159682 can significantly increase the efficacy of targeted cancer therapies with minimal adverse effects^[2].

Moreover, in the BJAB.Luc model, the efficacy of anti-CD22-NMS249 at a single dose of 2 mg/kg was comparable to that of anti-CD22-vc-MMAE, an established ADC. Both treatments achieved complete tumor remission, with anti-CD22-NMS249 leading to tumor stasis for up to three weeks. This comparative effectiveness, especially with complete remissions observed, indicates that PNU-159682 could play a crucial role in the development of more effective and potentially less toxic ADCs^[1].

PNU-159682 demonstrates profound cytotoxic effects on various human tumor cell lines, as revealed through the sulforhodamine B assay. The IC70 values showcase its potent activity, ranging from 0.081 nM to 0.577 nM against cell lines such as HT-29, A2780, DU145, EM-2, Jurkat, and CEM, indicating a high degree of cytotoxic efficiency^[1].

When compared to other therapeutic agents like MMDX and doxorubicin, PNU-159682's efficacy remains superior, with IC70 values spanning from 68 nM to 578 nM against MMDX, and even broader ranges of 181 nM to 1717 nM towards doxorubicin, emphasizing its potency^[1].

In cell viability assays against non-Hodgkin lymphoma (NHL) cell lines, PNU-159682's potency again surpasses that of MMAE, with IC50 values as low as 0.020 nM, compared to MMAE's IC50 values which are significantly higher^[2].

This trend continues in vitro with anti-CD22 antibody conjugates (anti-CD22-NMS249), where PNU-159682 enhances the efficacy of these antibody-drug conjugates (ADCs), yielding IC50 values that are 2 to 20 times more potent than pinatuzumab vedotin against similar NHL cell lines^[3].

Moreover, PNU-159682 demonstrates a marginal inhibition of topoisomerase II and specific cytotoxicity towards CAIX-expressing SKRC-52 cells, with an IC50 of 25 nM, suggesting a potential for targeting specific cancer markers^[4].