su-11248 and Uterine-Diseases

su-11248 has been researched along with Uterine-Diseases* in 1 studies

Other Studies

1 other study(ies) available for su-11248 and Uterine-Diseases

Article	Year
1,4-Dihydroindeno[1,2-c]pyrazoles with acetylenic side chains as novel and potent multitargeted receptor tyrosine kinase inhibitors with low affinity for the hERG ion channel. Journal of medicinal chemistry, 2007, May-03, Volume: 50, Issue:9 The synthesis of a novel series of 1,4-dihydroindeno[1,2-c]pyrazoles with acetylene-type side chains is described. Optimization of those compounds as KDR kinase inhibitors identified 8, which displayed an oral activity in an estradiol-induced murine uterine edema model (ED50 = 3 mg/kg) superior to Sutent (ED50 = 9 mg/kg) and showed potent antitumor efficacy in an MX-1 human breast carcinoma xenograft tumor growth model (tumor growth inhibition = 90% at 25 mg/kg.day po). The compound was docked into a homology model of the homo-tetrameric pore domain of the hERG potassium channel to identify strategies to improve its cardiac safety profile. Systematic interruption of key binding interactions between 8 and Phe656, Tyr652, and Ser624 yielded 90, which only showed an IC50 of 11.6 microM in the hERG patch clamp assay. The selectivity profile for 8 and 90 revealed that both compounds are multitargeted receptor tyrosine kinase inhibitors with low nanomolar potencies against the members of the VEGFR and PDGFR kinase subfamilies. Topics: Alkynes; Animals; Antineoplastic Agents; Binding, Competitive; Cell Line; Edema; ERG1 Potassium Channel; Estradiol; Ether-A-Go-Go Potassium Channels; Female; Humans; Indenes; Mice; Mice, Inbred BALB C; Models, Molecular; Patch-Clamp Techniques; Protein Binding; Pyrazoles; Radioligand Assay; Receptors, Platelet-Derived Growth Factor; Receptors, Vascular Endothelial Growth Factor; Stereoisomerism; Structure-Activity Relationship; Thiophenes; Uterine Diseases; Vascular Endothelial Growth Factor Receptor-2; Xenograft Model Antitumor Assays	2007

Article

Year

1,4-Dihydroindeno[1,2-c]pyrazoles with acetylenic side chains as novel and potent multitargeted receptor tyrosine kinase inhibitors with low affinity for the hERG ion channel.

Journal of medicinal chemistry, 2007, May-03, Volume: 50, Issue:9

The synthesis of a novel series of 1,4-dihydroindeno[1,2-c]pyrazoles with acetylene-type side chains is described. Optimization of those compounds as KDR kinase inhibitors identified 8, which displayed an oral activity in an estradiol-induced murine uterine edema model (ED50 = 3 mg/kg) superior to Sutent (ED50 = 9 mg/kg) and showed potent antitumor efficacy in an MX-1 human breast carcinoma xenograft tumor growth model (tumor growth inhibition = 90% at 25 mg/kg.day po). The compound was docked into a homology model of the homo-tetrameric pore domain of the hERG potassium channel to identify strategies to improve its cardiac safety profile. Systematic interruption of key binding interactions between 8 and Phe656, Tyr652, and Ser624 yielded 90, which only showed an IC50 of 11.6 microM in the hERG patch clamp assay. The selectivity profile for 8 and 90 revealed that both compounds are multitargeted receptor tyrosine kinase inhibitors with low nanomolar potencies against the members of the VEGFR and PDGFR kinase subfamilies.

Topics: Alkynes; Animals; Antineoplastic Agents; Binding, Competitive; Cell Line; Edema; ERG1 Potassium Channel; Estradiol; Ether-A-Go-Go Potassium Channels; Female; Humans; Indenes; Mice; Mice, Inbred BALB C; Models, Molecular; Patch-Clamp Techniques; Protein Binding; Pyrazoles; Radioligand Assay; Receptors, Platelet-Derived Growth Factor; Receptors, Vascular Endothelial Growth Factor; Stereoisomerism; Structure-Activity Relationship; Thiophenes; Uterine Diseases; Vascular Endothelial Growth Factor Receptor-2; Xenograft Model Antitumor Assays

2007