Moreover, in mouse tumor xenografts, S116836 significantly inhibits the growth and volume of tumors expressing the WT or T315I mutant BCR-ABL without causing significant cardiotoxicity.
The in vivo efficacy validation of p-niclosamide, a water soluble derivative of niclosamide, showed that p-niclosamide significantly inhibited the tumor burden of nude mice subcutaneously bearing T315I-BCR-ABL-expressing CML cells, and prolonged the survival of allografted leukemic mice harboring BaF3-T315I-BCR-ABL.
NVP-BEZ235 in combination with nilotinib also inhibited tumor growth in a xenograft model and inhibited the growth of primary T315I mutant cells and ponatinib-resistant cells.
AP24534 inhibited all tested BCR-ABL mutants in cellular and biochemical assays, suppressed BCR-ABL(T315I)-driven tumor growth in mice, and completely abrogated resistance in cell-based mutagenesis screens.