An inhibitor of tubulin polymerization and a PP2A activator
iHAP1 is an inhibitor of tubulin polymerization (IC50 = 0.87 ?M) and an allosteric activator of a heterotrimeric protein phosphatase 2A (PP2A) complex containing the PP2A-B56ε regulatory B subunit.1,2 It inhibits proliferation of K562 chronic myeloid leukemia (CML) cells (IC50 = 0.84 ?M), induces cell cycle arrest at the G2/M phase in KOPT-K1 T cell acute lymphoblastic leukemia (T-ALL) cells, and induces apoptosis in a variety of T-ALL cells (IC50s = 0.4-0.6 ?M). iHAP1 reduces the frequency of human CD45+ leukemia cells in the bone marrow, spleen, and liver and increases survival in a KOPT-K1 mouse xenograft model when administered at doses of 2.5 and 80 mg/kg per day.2
1.Prinz, H., Chamasmani, B., Vogel, K., et al.N-benzoylated phenoxazines and phenothiazines: Synthesis, antiproliferative activity, and inhibition of tubulin polymerizationJ. Med. Chem.54(12)4247-4263(2011) 2.Morita, K., He, S., Nowak, R.P., et al.Allosteric activators of protein phosphatase 2A display broad antitumor activity mediated by dephosphorylation of MYBL2Cell181(3)702-715(2020)
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