xmd-8-92 and Neoplasms

xmd-8-92 has been researched along with Neoplasms* in 2 studies

Other Studies

2 other study(ies) available for xmd-8-92 and Neoplasms

Article	Year
Targeting the BMK1 MAP kinase pathway in cancer therapy. Clinical cancer research : an official journal of the American Association for Cancer Research, 2011, Jun-01, Volume: 17, Issue:11 The big mitogen activated protein kinase 1 (BMK1) pathway is the most recently discovered and least-studied mammalian mitogen-activated protein (MAP) kinase cascade, ubiquitously expressed in all types of cancer cells tested so far. Mitogens and oncogenic signals strongly activate this cellular MAP kinase pathway, thereby passing down proliferative, survival, chemoresistance, invasive, and angiogenic signals in tumor cells. Recently, several pharmacologic small molecule inhibitors of this pathway have been developed. Among them, the BMK1 inhibitor XMD8-92 blocks cellular BMK1 activation and significantly suppresses tumor growth in lung and cervical tumor models and is well tolerated in animals. On the other hand, MEK5 inhibitors, BIX02188, BIX02189, and compound 6, suppress cellular MEK5 activity, but no data exist to date on their effectiveness in animals. Topics: Animals; Antineoplastic Agents; Benzodiazepinones; Cell Cycle; Humans; MAP Kinase Kinase 5; MAP Kinase Signaling System; Mice; Mice, Knockout; Mitogen-Activated Protein Kinase 7; Neoplasm Metastasis; Neoplasms; Neovascularization, Pathologic	2011
Pharmacological inhibition of BMK1 suppresses tumor growth through promyelocytic leukemia protein. Cancer cell, 2010, Sep-14, Volume: 18, Issue:3 BMK1 is activated by mitogens and oncogenic signals and, thus, is strongly implicated in tumorigenesis. We found that BMK1 interacted with promyelocytic leukemia protein (PML), and inhibited its tumor-suppressor function through phosphorylation. Furthermore, activated BMK1 notably inhibited PML-dependent activation of p21. To further investigate the BMK-mediated inhibition of the tumor suppressor activity of PML in tumor cells, we developed a small-molecule inhibitor of the kinase activity of BMK1, XMD8-92. Inhibition of BMK1 by XMD8-92 blocked tumor cell proliferation in vitro and significantly inhibited tumor growth in vivo by 95%, demonstrating the efficacy and tolerability of BMK1-targeted cancer treatment in animals. Topics: Animals; Cell Growth Processes; Cell Nucleus; Cytosol; Genes, Tumor Suppressor; HeLa Cells; Humans; Mitogen-Activated Protein Kinase 7; Neoplasms; Nuclear Proteins; Phosphorylation; Promyelocytic Leukemia Protein; Protein Kinase Inhibitors; Signal Transduction; Transcription Factors; Tumor Suppressor Proteins	2010

Article

Year

Targeting the BMK1 MAP kinase pathway in cancer therapy.

Clinical cancer research : an official journal of the American Association for Cancer Research, 2011, Jun-01, Volume: 17, Issue:11

The big mitogen activated protein kinase 1 (BMK1) pathway is the most recently discovered and least-studied mammalian mitogen-activated protein (MAP) kinase cascade, ubiquitously expressed in all types of cancer cells tested so far. Mitogens and oncogenic signals strongly activate this cellular MAP kinase pathway, thereby passing down proliferative, survival, chemoresistance, invasive, and angiogenic signals in tumor cells. Recently, several pharmacologic small molecule inhibitors of this pathway have been developed. Among them, the BMK1 inhibitor XMD8-92 blocks cellular BMK1 activation and significantly suppresses tumor growth in lung and cervical tumor models and is well tolerated in animals. On the other hand, MEK5 inhibitors, BIX02188, BIX02189, and compound 6, suppress cellular MEK5 activity, but no data exist to date on their effectiveness in animals.

Topics: Animals; Antineoplastic Agents; Benzodiazepinones; Cell Cycle; Humans; MAP Kinase Kinase 5; MAP Kinase Signaling System; Mice; Mice, Knockout; Mitogen-Activated Protein Kinase 7; Neoplasm Metastasis; Neoplasms; Neovascularization, Pathologic

2011

Pharmacological inhibition of BMK1 suppresses tumor growth through promyelocytic leukemia protein.

Cancer cell, 2010, Sep-14, Volume: 18, Issue:3

BMK1 is activated by mitogens and oncogenic signals and, thus, is strongly implicated in tumorigenesis. We found that BMK1 interacted with promyelocytic leukemia protein (PML), and inhibited its tumor-suppressor function through phosphorylation. Furthermore, activated BMK1 notably inhibited PML-dependent activation of p21. To further investigate the BMK-mediated inhibition of the tumor suppressor activity of PML in tumor cells, we developed a small-molecule inhibitor of the kinase activity of BMK1, XMD8-92. Inhibition of BMK1 by XMD8-92 blocked tumor cell proliferation in vitro and significantly inhibited tumor growth in vivo by 95%, demonstrating the efficacy and tolerability of BMK1-targeted cancer treatment in animals.

Topics: Animals; Cell Growth Processes; Cell Nucleus; Cytosol; Genes, Tumor Suppressor; HeLa Cells; Humans; Mitogen-Activated Protein Kinase 7; Neoplasms; Nuclear Proteins; Phosphorylation; Promyelocytic Leukemia Protein; Protein Kinase Inhibitors; Signal Transduction; Transcription Factors; Tumor Suppressor Proteins

2010