Leads discovered by chemical library screening

Screening of several combinatorial libraries using an enzyme de-repression assay that measures relief of XIAP-mediated suppression of caspase-3 led to the identification of a series of polyphenylureas exemplified by 35 [86,87]. Unlike the peptides derived from the SMAC N-terminus, the active polyphenylureas were shown to inhibit XIAP by binding to the BIR2 domain of XIAP, consequently leading to the activation of downstream executioner caspases-3 and 7. These compounds, but not inactive controls, induced rapid apoptosis in several tumor cell lines. Urea 35 induced significant tumor growth delay in PPC1 prostate cancer and HCT116 colon cancer murine xenograft models, but displayed little toxicity to normal tissues at high concentrations.


Using a similar high-throughput screening approach to that described above, a series of compounds, exemplified by phenylsulfonamide 36, was identified from a combinatorial library [88]. Compound 36 disrupts the XIAP/caspase-3 interaction in vitro and synergizes with death receptor stimulation to bypass the apoptotic block resulting from the loss of the pro-apoptotic protein Bax in the colon carcinoma cell line HCT116.

Supplements For Diabetics

Supplements For Diabetics

All you need is a proper diet of fresh fruits and vegetables and get plenty of exercise and you'll be fine. Ever heard those words from your doctor? If that's all heshe recommends then you're missing out an important ingredient for health that he's not telling you. Fact is that you can adhere to the strictest diet, watch everything you eat and get the exercise of amarathon runner and still come down with diabetic complications. Diet, exercise and standard drug treatments simply aren't enough to help keep your diabetes under control.

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