||In addition to inducing rapid down-regulation of Bcr/Abl without affecting Bcr or c-Abl, WP1130 also regulates the stability of Jak2 and c-Myc without affecting other kinases (HER1, HER2, c-Kit, FAK, ERK1, ERK2, Akt, Btk, Src and Src-related kinases) or transcription factors (wild-type p53, STAT1, STAT3, STAT5, c-Jun, NF-κB, and Max). Unlike adaphostin and Trisenox, WP1130 induces down-regulation of Bcr/Abl within 60 minutes. WP1130 is more effective in inducing apoptosis of myeloid and lymphoid tumor cells with IC50 of ~0.5-2.5 μM compared with normal CD34+ hematopoietic precursors, dermal fibroblasts, or endothelial cells with IC50 of ~5-10 μM. WP1130 (5 μM) specifically and rapidly down-regulates both wild-type and T315I mutant Bcr/Abl protein without affecting bcr/abl gene expression or engaging the proteasomal degradation pathway in chronic myelogenous leukemia (CML) cells, accompanied by induction of apoptosis. WP1130 is more effective in reducing leukemic cell colony formation compared with normal progenitor cells, and effective against primary leukemic cells harboring the T315I mutation.  WP1130 induces rapid proteasomal-dependent degradation of c-Myc protein in MM-1 multiple myeloma and other tumor cell lines, correlated with tumor growth inhibition.  Unlike AG490, WP1130 acts as a partly selective deubiquitinase (DUB) inhibitor to induce a rapid and marked accumulation of polyubiquitinated (K48/K63-linked) proteins into juxtanuclear aggresomes without affecting proteasome activity. WP1130 (5 μM) directly inhibits DUB activity of USP9x, USP5, USP14, UCH-L1, and UCH37, but not UCH-L3, resulting in downregulation of antiapoptotic and upregulation of proapoptotic proteins, such as MCL-1 and p53.