Endothall

Endothall (Endothal) is a protein phosphatase 2A (PP2A) inhibitor with IC₅₀s of 90 nM and 5 µM for PP2A and PP1, respectively. Endothall can be used as an herbicide. Endothall also is useful in cancer chemotherapy^[1]. In Vitro: Endothall, an organic acid, is the least toxic structural analogue of Cantharidin that still inhibits PP2A^[2].
Endothall inhibits preferentially hepatocellular carcinoma (HCC) growth and these new rat hepatocellular carcinoma lines may be useful for further biochemical and pharmacological studies on PP2A inhibitors, and for testing new forms of treatment of hepatic cell carcinomas. The HR-2, HR-3, HR-4, and Zajdela hepatocellular carcinomas are most sensitive to Endothall (IC₅₀ of 1.7, 1.2, 0.9, and 1.7 µg/mL), whereas newborn rat hepatocytes growing exponentially in primary culture (IC₅₀=6.2 µg/mL), rat DHD/K12 colon carcinoma cells (IC₅₀=3.6 µg/mL), or human HT-29 colon carcinoma cells (IC₅₀=4.9 µg/mL) were less sensitive^[2].
Endothall inhibits the growth of HCC lines in culture more than that of normal hepatocytes or colon carcinomas, inducing mitotic arrest, followed by cell death. Endothall causes dose- and time-dependent cytostasis specifically in G2/M^[2].
Endothall (3 µg/mL) inhibits the cell cycle at G2/M and subsequent apoptotic cell death^[2]. In Vivo: Endothall exhibits acute LD₅₀ of 14 mg/kg in mice^[2].