Compounds > n-(4-methoxybenzyl)-n--(5-nitro-1-3-thiazol-2-yl)urea

n-(4-methoxybenzyl)-n--(5-nitro-1-3-thiazol-2-yl)urea and enzastaurin

n-(4-methoxybenzyl)-n--(5-nitro-1-3-thiazol-2-yl)urea has been researched along with enzastaurin* in 1 studies

Other Studies

1 other study(ies) available for n-(4-methoxybenzyl)-n--(5-nitro-1-3-thiazol-2-yl)urea and enzastaurin

Article	Year
Inhibition of glycogen synthase kinase-3 increases the cytotoxicity of enzastaurin. The Journal of investigative dermatology, 2011, Volume: 131, Issue:7 Cutaneous T-cell lymphomas (CTCL) represent a spectrum of several distinct non-Hodgkin's lymphomas that are characterized by an invasion of the skin by malignant, clonal lymphocytes. Our laboratory has previously demonstrated that the protein kinase C (PKC) β inhibitor Enzastaurin increases apoptosis in malignant lymphocytes of CTCL. These results directly led to a clinical trial for Enzastaurin in CTCL in which it was well tolerated and showed modest activity. To ascertain a means of improving the efficacy of Enzastaurin, we investigated complementary signaling pathways and identified glycogen synthase kinase-3 (GSK3) as important in survival signaling in CTCL. Enzastaurin combined with GSK3 inhibitors demonstrated an enhancement of cytotoxicity. Treatment with a combination of Enzastaurin and the GSK3 inhibitor AR-A014418 resulted in upregulation of β-catenin total protein and β-catenin-mediated transcription. Inhibition of β-catenin-mediated transcription or small hairpin RNA (shRNA) knockdown of β-catenin decreased the cytotoxic effects of Enzastaurin plus AR-A014418. In addition, treatment with Enzastaurin and AR-A014418 decreased the mRNA levels and surface expression of CD44. shRNA knockdown of β-catenin also restored CD44 surface expression. Our observations provide a rationale for the combined targeting of PKC and GSK3 signaling pathways in CTCL to enhance the therapeutic outcome. Topics: Antineoplastic Agents; beta Catenin; Cells, Cultured; Glycogen Synthase Kinase 3; Humans; Hyaluronan Receptors; Indoles; Lymphoma, T-Cell, Cutaneous; Protein Kinase C; Protein Kinase Inhibitors; Skin Neoplasms; TCF Transcription Factors; Thiazoles; Urea	2011

Article

Year

Inhibition of glycogen synthase kinase-3 increases the cytotoxicity of enzastaurin.

The Journal of investigative dermatology, 2011, Volume: 131, Issue:7

Cutaneous T-cell lymphomas (CTCL) represent a spectrum of several distinct non-Hodgkin's lymphomas that are characterized by an invasion of the skin by malignant, clonal lymphocytes. Our laboratory has previously demonstrated that the protein kinase C (PKC) β inhibitor Enzastaurin increases apoptosis in malignant lymphocytes of CTCL. These results directly led to a clinical trial for Enzastaurin in CTCL in which it was well tolerated and showed modest activity. To ascertain a means of improving the efficacy of Enzastaurin, we investigated complementary signaling pathways and identified glycogen synthase kinase-3 (GSK3) as important in survival signaling in CTCL. Enzastaurin combined with GSK3 inhibitors demonstrated an enhancement of cytotoxicity. Treatment with a combination of Enzastaurin and the GSK3 inhibitor AR-A014418 resulted in upregulation of β-catenin total protein and β-catenin-mediated transcription. Inhibition of β-catenin-mediated transcription or small hairpin RNA (shRNA) knockdown of β-catenin decreased the cytotoxic effects of Enzastaurin plus AR-A014418. In addition, treatment with Enzastaurin and AR-A014418 decreased the mRNA levels and surface expression of CD44. shRNA knockdown of β-catenin also restored CD44 surface expression. Our observations provide a rationale for the combined targeting of PKC and GSK3 signaling pathways in CTCL to enhance the therapeutic outcome.

Topics: Antineoplastic Agents; beta Catenin; Cells, Cultured; Glycogen Synthase Kinase 3; Humans; Hyaluronan Receptors; Indoles; Lymphoma, T-Cell, Cutaneous; Protein Kinase C; Protein Kinase Inhibitors; Skin Neoplasms; TCF Transcription Factors; Thiazoles; Urea

2011