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2.
Figure 1

Figure 1. From: Lipophilic Lysine-Spermine Conjugates are Potent Polyamine Transport Inhibitors for use in Combination with a Polyamine Biosynthesis Inhibitor.

Cellular polyamine depletion therapy: Synthesis, recycling and transport must be considered.

Mark R. Burns, et al. J Med Chem. ;52(7):1983-1993.
3.
Figure 4

Figure 4. From: Lipophilic Lysine-Spermine Conjugates are Potent Polyamine Transport Inhibitors for use in Combination with a Polyamine Biosynthesis Inhibitor.

HCPC Growth Inhibition with PTI and DFMO.a
aHCPC cells cultured for 6 days in combination with 5.0 mM DFMO, 0.5 µM spermidine and 1.0 mM aminoguanidine together with the amount of Lys-spm conjugates shown.

Mark R. Burns, et al. J Med Chem. ;52(7):1983-1993.
4.
Figure 3

Figure 3. From: Lipophilic Lysine-Spermine Conjugates are Potent Polyamine Transport Inhibitors for use in Combination with a Polyamine Biosynthesis Inhibitor.

Comparison of growth-inhibitory activities against A375 cells between unsubstituted (5) and lipophilic Lys-spm (10) conjugates in combination with DFMO.a
aA375 cells cultured for 6 days in combination with 5.0 mM DFMO, 0.5 µM spermidine and 1.0 mM aminoguanidine together with the amount of Lys-spm conjugates shown.

Mark R. Burns, et al. J Med Chem. ;52(7):1983-1993.
5.
Figure 5

Figure 5. From: Lipophilic Lysine-Spermine Conjugates are Potent Polyamine Transport Inhibitors for use in Combination with a Polyamine Biosynthesis Inhibitor.

Cellular polyamine depletion using the combination of PTI and DFMO.a
aConditions: MDA-MB-231 cells were treated for 5 days with 30 µM 5 (D-Lys-spm) or 0.1 µM 11 (Lipo-PA), 5.0 mM DFMO, or the combination of both Lys-spm conjugate and DFMO (all with 0.5 µM spermidine and 1.0 mM aminoguanidine). Polyamine levels determined by pre-column dansylation followed by fluorescent HPLC detection.

Mark R. Burns, et al. J Med Chem. ;52(7):1983-1993.
6.
Figure 8

Figure 8. From: Lipophilic Lysine-Spermine Conjugates are Potent Polyamine Transport Inhibitors for use in Combination with a Polyamine Biosynthesis Inhibitor.

Antitumor activity following oral delivery of PTI analog 11 (~3 mg/kg) and DFMOa.
aResponse of 6 tumors to 6 weeks of a combined treatment with 0.5% DFMO and 11 both given in the drinking water. Numbers above each set represent the ratio of tumor volume at the end of the trial period divided by the initial pretreatment volume.

Mark R. Burns, et al. J Med Chem. ;52(7):1983-1993.
7.
Figure 7

Figure 7. From: Lipophilic Lysine-Spermine Conjugates are Potent Polyamine Transport Inhibitors for use in Combination with a Polyamine Biosynthesis Inhibitor.

Antitumor effects in SCC mouse model using combination of DFMO and agent 27.a
aResponse of 17 tumors to 4 weeks of a combined treatment with 0.5% DFMO and 0.5 mg/kg 27 (i.p. twice daily). Numbers above each set represent the ratio of each tumor volume: tumor volume at the end of the trial period divided by the initial pretreatment volume. "–" represents complete disappearance of the tumor.

Mark R. Burns, et al. J Med Chem. ;52(7):1983-1993.
8.
Figure 6

Figure 6. From: Lipophilic Lysine-Spermine Conjugates are Potent Polyamine Transport Inhibitors for use in Combination with a Polyamine Biosynthesis Inhibitor.

Antitumor effects in SCC mouse model using either PTI analog 11 alone or combination of DFMO and agent 11.a
aResponse of SCC tumors to 4 weeks of treatment with Cmpd 11 alone (TOP; 0.5 mg/kg twice daily) or combined treatment with 0.5% DFMO orally and 11 (BOTTOM; 0.5 mg/kg i.p. twice daily). Numbers above each set represent the ratio of each tumor volume: tumor volume at the end of the trial period divided by the initial pretreatment volume. "–" represents complete disappearance of the tumor.

Mark R. Burns, et al. J Med Chem. ;52(7):1983-1993.

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