IC50 Value: 1.09 uM (MTT assay in LNCaP-S14 cells) [1] SMIP004 (N-(4-butyl-2-methyl-phenyl) acetamide) is a novel inducer of cancer-cell selective apoptosis of human prostate cancer cells. Unlike SMIP001, SMIP004 was found to downregulate SKP2 and to stabilize p27, although neither SMIP is a proteasome inhibitor. in vitro: Whereas SMIP012 and 016 were moderately toxic in normal fibroblasts, SMIPs 001 and 004 showed substantial cancer cell specificity being at least five times more potent in LNCaP-S14 than in IMR90 cells , treatment with either MG132 or SMIP004 increased p27 half-life to > 6 h [1]. Both SMIP001 and 004 led to a strong increase in the recruitment of p27 to CDK2, while SMIP001 also slightly increased coprecipitation of p21 (Figure 6c). SMIP004 also reduced the amounts of cyclins E and A retrieved with CDK2. This was paralleled by a marked downregulation of cyclins E and A upon SMIP004 treatment. SMIP004 decreased the levels of positive cell cycle regulators, upregulated cyclin-dependent kinase inhibitors, and resulted in G1 arrest, inhibition of colony formation in soft agar, and cell death [2]. in vivo: SMIP004 potently inhibits the growth of prostate and breast cancer xenografts in mice [2]. Clinical trial: N/A