smac-mimetic sm83  (SMAC Corp)

Journal: Computational and Structural Biotechnology Journal

Article Title: Structure-based identification of a new IAP-targeting compound that induces cancer cell death inducing NF-κB pathway

doi: 10.1016/j.csbj.2021.11.034

Figure Lengend Snippet: Enhanced FC2 cytotoxic activity in presence of SM. Effect on cell viability of the combination of FC2 and SM83: (A) MDA-MB-231 and (B) SK-OV3 cells pretreated with different concentration of SM83, followed by addition of FC2 [0 (white bars), 12.5 (grey bars) and 100 μM (black bars)]. The experiments were repeated both in technical (three for each experiment) and biological (three independent experiments) triplicate. Mean values ± Standard deviation are shown.

Article Snippet: Such an effect is more pronounced when FC2 is administered in combination with TNF or with the Smac-mimetic SM83 (namely 9a) , in two out of three cancer cell lines tested.

Techniques: Activity Assay, Concentration Assay, Standard Deviation

Journal: NPJ Systems Biology and Applications

Article Title: Systemic network analysis identifies XIAP and IκBα as potential drug targets in TRAIL resistant BRAF mutated melanoma

doi: 10.1038/s41540-018-0075-y

Figure Lengend Snippet: Depletion of XIAP re-sensitizes melanoma cells to IZI1551. a IZI1551-conditioned A375 melanoma cells were transiently transfected with an IκBα super repressor (IκBα-SR) or the empty vector (mock) and treated with IZI1551 (50 ng/ml). After 16 h apoptosis was determined using a CDDE (* p ≤ 0.05; n.s. = not significant) and b the status of IκBα, p-p65(Ser536), p65, and XIAP monitored by Western-blot analysis. GAPDH served as loading control. c Transcription was inhibited in parental and IZI1551-conditioned A375 cells by addition of Actinomycin D (ActD, 1 µM) for the indicated time points. Protein level of XIAP was monitored by Western-blot analysis. GAPDH served as loading control. d XIAP was depleted from parental and IZI1551-conditioned A375 and f Malme3M cells using RNAi for 72 h. Sixteen hours after treatment with IZI1551 (50 ng/ml) apoptosis was determined using a CDDE (*** p ≤ 0.001) and e , g the status of XIAP, p-p65(Ser536), and p65 monitored by Western-blot analysis. β-actin served as loading control. h Parental and IZI-conditioned A375 melanoma cells were treated with IZ1551 (50 ng/ml) or increasing doses of the smac mimetic SM83 (0.1, 1, 10 µM) alone or in combination. After 16 h apoptosis was determined using a CDDE (** p ≤ 0.01) and i the status of XIAP monitored by Western-blot analysis. GAPDH served as loading control. j For five unstimulated mut BRAF melanoma cell lines the relative expression of XIAP was determined by semi-quantitative Western-blot analysis and k the apoptotic response to IZI1551 (50 ng/ml) determined after 16 h using a CDDE (*** p ≤ 0.001). For CDDE the mean ± SD of three independently performed experiments is shown. WBs represent one out of three independently performed experiments

Article Snippet: To that effect, we showed co-stimulation with the SMAC mimetic SM83 to fully re-sensitize melanoma cells to IZI1551 that had acquired secondary resistance to the TRAIL-agonist via XIAP depletion.

Techniques: Transfection, Plasmid Preparation, Western Blot, Expressing