Journal: Journal of Medicinal Chemistry

Article Title: Structure-Based Design of Potent Bcl-2/Bcl-xL Inhibitors with Strong in Vivo Antitumor Activity

doi: 10.1021/jm300608w

Figure Lengend Snippet: Figure 7. (A) Representative cell growth inhibition of 12, 14, 15, and 1 in three small-cell lung cancer cell lines. (B) Cell death induction by 12, 14, 15, and 1 in H146 cell line. Cells were treated for 24 h, and cell death was analyzed by trypan blue assay. (C) Induction of cleavage of PARP and caspase-3 in H146 cell line by 12, 14, 15, and 1. Cells were treated for 24 h, and caspase-3 (Cas 3) and PARP were probed by Western blotting: Cl PARP, cleaved PARP; Cl Cas 3, cleaved caspase-3. GAPDH was used as the loading control.

Article Snippet: These assays were performed as previously described.17 Human smallcell lung cancer cell lines H146 and H1417 were purchased from American Type Culture Collection (ATCC) and were maintained in dx.doi.org/10.1021/jm300608w | J. Med.

Techniques: Inhibition, Western Blot, Control

Journal: Journal of Medicinal Chemistry

Article Title: Structure-Based Design of Potent Bcl-2/Bcl-xL Inhibitors with Strong in Vivo Antitumor Activity

doi: 10.1021/jm300608w

Figure Lengend Snippet: Figure 8. Analysis of cytochrome c (Cyto c) release from mitochondria into cytosol and cleavage of PARP (Cl PARP) induced by 14 and 15 in H146 cells in 2 h. GAPDH was used as the loading control.

Article Snippet: These assays were performed as previously described.17 Human smallcell lung cancer cell lines H146 and H1417 were purchased from American Type Culture Collection (ATCC) and were maintained in dx.doi.org/10.1021/jm300608w | J. Med.

Techniques: Control

Journal: Journal of Medicinal Chemistry

Article Title: Structure-Based Design of Potent Bcl-2/Bcl-xL Inhibitors with Strong in Vivo Antitumor Activity

doi: 10.1021/jm300608w

Figure Lengend Snippet: Figure 9. Analysis of induction of cleavage of PARP and caspase-3 in the H146 xenograft tumor tissues by 14 (25 mg/kg, iv). Mice bearing H146 xenograft tumors were dosed with either 14 or vehicle. Animals were sacrificed at 3, 6, and 24 h time points, and tumor tissues were analyzed by Western blot for cleavage of PARP (Cl PARP) and caspase-3 (Cl caspase-3). GAPDH was used as the loading control.

Article Snippet: These assays were performed as previously described.17 Human smallcell lung cancer cell lines H146 and H1417 were purchased from American Type Culture Collection (ATCC) and were maintained in dx.doi.org/10.1021/jm300608w | J. Med.

Techniques: Western Blot, Control

Journal: Journal of Medicinal Chemistry

Article Title: Structure-Based Design of Potent Bcl-2/Bcl-xL Inhibitors with Strong in Vivo Antitumor Activity

doi: 10.1021/jm300608w

Figure Lengend Snippet: Figure 10. Antitumor activity of compound 14 in H146 xenograft model. H146 tumor cells were injected subcutaneously into SCID mice, and treatments started when tumors reached a mean volume of 70 mm3. Each group consisted of eight mice/tumors.

Article Snippet: These assays were performed as previously described.17 Human smallcell lung cancer cell lines H146 and H1417 were purchased from American Type Culture Collection (ATCC) and were maintained in dx.doi.org/10.1021/jm300608w | J. Med.

Techniques: Activity Assay, Injection