Journal: Journal of Medicinal Chemistry

Article Title: Design of Bcl-2 and Bcl-xL Inhibitors with Subnanomolar Binding Affinities Based Upon a New Scaffold

doi: 10.1021/jm300178u

Figure Lengend Snippet: Binding affinities of our designed compounds to Bcl-2 and Bcl-X L proteins in our FP-based assays and inhibition of cell growth in two cancer cell lines.

Article Snippet: Human small cell lung cancer cell lines H146 and H1417 were purchased from the American Type Culture Collection (ATCC) and were maintained in RPMI-1640 medium containing 10% FBS.

Techniques: Binding Assay, Inhibition

Journal: Journal of Medicinal Chemistry

Article Title: Design of Bcl-2 and Bcl-xL Inhibitors with Subnanomolar Binding Affinities Based Upon a New Scaffold

doi: 10.1021/jm300178u

Figure Lengend Snippet: Binding affinities of our designed compounds to Bcl-2 and Bcl-X L proteins in FP-based assays and inhibition of cell growth in two small-cell lung cancer cell lines.

Article Snippet: Human small cell lung cancer cell lines H146 and H1417 were purchased from the American Type Culture Collection (ATCC) and were maintained in RPMI-1640 medium containing 10% FBS.

Techniques: Binding Assay, Inhibition

Journal: Journal of Medicinal Chemistry

Article Title: Design of Bcl-2 and Bcl-xL Inhibitors with Subnanomolar Binding Affinities Based Upon a New Scaffold

doi: 10.1021/jm300178u

Figure Lengend Snippet: (A). Cell death induction by 20 and 21 in the H146 cancer cell line. Cells were treated for 24 h and cell death was analyzed by trypan blue assay. (B). Induction of cleavage of PARP and caspase-3 by 20 and 21 in the H146 cell line. Cells were treated for 24 h and caspase-3 and PARP were probed by western blotting.

Article Snippet: Human small cell lung cancer cell lines H146 and H1417 were purchased from the American Type Culture Collection (ATCC) and were maintained in RPMI-1640 medium containing 10% FBS.

Techniques: Western Blot

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: Binding affinities of designed and reference compounds to Bcl-2, Bcl-xL and Mcl-1 proteins and inhibition of cell growth in three small-cell lung cancer cell lines.

Article Snippet: To develop xenograft tumors, 5 × 10 6 H146 cancer cells with matrigel were injected subcutaneously on the dorsal side of the SCID mice (from Charles River), one tumor per mouse.

Techniques: Binding Assay, Inhibition

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: (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: To develop xenograft tumors, 5 × 10 6 H146 cancer cells with matrigel were injected subcutaneously on the dorsal side of the SCID mice (from Charles River), one tumor per mouse.

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: 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: To develop xenograft tumors, 5 × 10 6 H146 cancer cells with matrigel were injected subcutaneously on the dorsal side of the SCID mice (from Charles River), one tumor per mouse.

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: Analysis of induction of cleavage of PARP and caspase-3 in the H146 xenograft tumor tissues by 14 (25 mg/kg, i.v.). Mice bearing H146 xenograft tumors were dosed with either 14 or vehicle. Animals were sacrificed at 3, 6 and 24 hr 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: To develop xenograft tumors, 5 × 10 6 H146 cancer cells with matrigel were injected subcutaneously on the dorsal side of the SCID mice (from Charles River), one tumor per mouse.

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: 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 8 mice/tumors.

Article Snippet: To develop xenograft tumors, 5 × 10 6 H146 cancer cells with matrigel were injected subcutaneously on the dorsal side of the SCID mice (from Charles River), one tumor per mouse.

Techniques: Activity Assay, Injection