Halistatins are highly potent polyether macrolides with anti-mitotic actions that were originally isolated from certain marine sponges. Similar polyether macrolides, such as, Bryostatin 1 (Ph2), Halichondrin B (PC) and its analog, E7389 (Ph 2), are being tested both preclinically and clinically as anti-cancer agents.

Halistatin 1 has highly potent cytotoxic activity in vitro against P388 cells (ED50 of 4x10-4 ?g/mL) and against 60 human cancer cell lines from the NCI’s anti-tumor screening panel (average overall panel GI50 of 7x10-10 M).

Halistatin 2 has highly potent cytotoxic activity in vitro against P388 cells (ED50 of 4x10-4 ?g/mL) and against 60 human cancer cell lines from the NCI’s anti-tumor screening panel (average overall panel GI50 of 7x10-10 M).

Halistatin 3 strongly inhibits growth (ED50 of 3.5x10-5 ?g/mL) of P388 leukemia cells and a ‘mini’ panel of human cancer cell lines (GI50, ?g/mL): brain (SF-295, 3.5x10-5), lung (NCI-460, 2.5x10-5), colon (KM 2062, 5.1x10-6), ovary (OVCAR-3, 1.3x10-5), renal (A498, 5.6x10-5) and melanoma (SK-MEL-5, 2.5x10-5).

Potential Applications

These novel compounds have applications as:

• Anti-cancer therapeutic agents

Benefits and Advantages

• Diversity – The new compounds are structural analogs of confirmed very potent candidates for anti-cancer drugs.
• Efficacy – The new compounds also possess promising anti-mitotic activities.