In this study we examined the anti-leukemia activity of a small molecule inhibitor of Hsp70 proteins, apoptozole (Az), and hybrids in which it is linked to an inhibitor of either Hsp90 (geldanamycin) or Abl kinase (imatinib). The results of NMR studies revealed that Az associates with an ATPase domain of Hsc70 and thus blocks ATP binding to the protein. Observations made in the cell study indicated that Az treatment promotes leukemia cell death by activating caspase-dependent apoptosis without affecting the caspase-independent apoptotic pathway. Importantly, the hybrids composed of Az and geldanamycin, which have high inhibitory activities towards both Hsp70 and Hsp90, exhibit enhanced anti-leukemia activity relative to the individual inhibitors. However, the Az and imatinib hybrids have weak inhibitory activities towards Hsp70 and Abl, and display lower cytotoxicity against leukemia cells compared to those of the individual constituents. The results of a mechanistic study showed that the active hybrid molecules promote leukemia cell death through a caspase-dependent apoptotic pathway. Taken together, the findings suggest that Hsp70 inhibitors as well as their hybrids can serve as potential anti-leukemia agents.

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The effect of metal turnover (MTO) of electroless Ni plating bath on the brittle fracture behavior of electroless nickel electroless palladium immersion gold (ENEPIG)/Sn-3.0wt%Ag-0.5wt%Cu(SAC305) solder joint was evaluated in this study. The MTOs of the electroless Ni for the ENEPIG surface finish were 0 and 3. As the MTO increased, the interfacial IMC thickness increased. The brittle fracture behavior of the ENEPIG/SAC305 solder joint was evaluated with high speed shear (HSS) test. The HSS strength decreased with increasing the MTO of the electroless Ni bath. The brittle fracture increased with increasing the shear speed of the HSS test. The percentage of the brittle fracture for the 3 MTO sample was much higher than that for the 0 MTO sample.