mln8054 and Colonic-Neoplasms

mln8054 has been researched along with Colonic-Neoplasms* in 1 studies

Other Studies

1 other study(ies) available for mln8054 and Colonic-Neoplasms

Article	Year
Synthesis, SAR and biological evaluation of 1,6-disubstituted-1H-pyrazolo[3,4-d]pyrimidines as dual inhibitors of Aurora kinases and CDK1. Bioorganic & medicinal chemistry letters, 2012, Mar-01, Volume: 22, Issue:5 Since the early 2000s, the Aurora kinases have become major targets of oncology drug discovery particularly Aurora-A and Aurora-B kinases (AKA/AKB) for which the selective inhibition in cells lead to different phenotypes. In addition to targeting these Aurora kinases involved in mitosis, CDK1 has been added as a primary inhibition target in hopes of enhancing the cytotoxicity of our chemotypes harboring the pyrazolopyrimidine core. SAR optimization of this series using the AKA, AKB and CDK1 biochemical assays led to the discovery of the compound 7h which combines strong potency against the 3 kinases with an acceptable microsomal stability. Finally, switching from a primary amide to a two-substituted pyrrolidine amide gave rise to compound 15a which exhibited the desired AKA/CDK1 inhibition phenotype in cells but showed moderate activity in animal models using HCT116 tumor cell lines. Topics: Animals; Antineoplastic Agents; Aurora Kinase A; Aurora Kinase B; Aurora Kinases; CDC2 Protein Kinase; Cell Line; Colon; Colonic Neoplasms; HCT116 Cells; Humans; Mice; Models, Molecular; Protein Kinase Inhibitors; Protein Serine-Threonine Kinases; Pyrazoles; Pyrimidines; Rats; Structure-Activity Relationship	2012

Article

Year

Synthesis, SAR and biological evaluation of 1,6-disubstituted-1H-pyrazolo[3,4-d]pyrimidines as dual inhibitors of Aurora kinases and CDK1.

Bioorganic & medicinal chemistry letters, 2012, Mar-01, Volume: 22, Issue:5

Since the early 2000s, the Aurora kinases have become major targets of oncology drug discovery particularly Aurora-A and Aurora-B kinases (AKA/AKB) for which the selective inhibition in cells lead to different phenotypes. In addition to targeting these Aurora kinases involved in mitosis, CDK1 has been added as a primary inhibition target in hopes of enhancing the cytotoxicity of our chemotypes harboring the pyrazolopyrimidine core. SAR optimization of this series using the AKA, AKB and CDK1 biochemical assays led to the discovery of the compound 7h which combines strong potency against the 3 kinases with an acceptable microsomal stability. Finally, switching from a primary amide to a two-substituted pyrrolidine amide gave rise to compound 15a which exhibited the desired AKA/CDK1 inhibition phenotype in cells but showed moderate activity in animal models using HCT116 tumor cell lines.

Topics: Animals; Antineoplastic Agents; Aurora Kinase A; Aurora Kinase B; Aurora Kinases; CDC2 Protein Kinase; Cell Line; Colon; Colonic Neoplasms; HCT116 Cells; Humans; Mice; Models, Molecular; Protein Kinase Inhibitors; Protein Serine-Threonine Kinases; Pyrazoles; Pyrimidines; Rats; Structure-Activity Relationship

2012