Fragment-based design, synthesis, biological evaluation, and SAR of 1H-benzo[d]imidazol-2-yl)-1H-indazol derivatives as potent PDK1 inhibitors.

Chen, Ting; Sorna, Venkataswamy; Choi, Susie; Call, Lee; Bearss, Jared; Carpenter, Kent; Warner, Steven L; Sharma, Sunil; Bearss, David J; Vankayalapati, Hariprasad

Chen, Ting; Sorna, Venkataswamy; Choi, Susie; Call, Lee; Bearss, Jared; Carpenter, Kent; Warner, Steven L; Sharma, Sunil; Bearss, David J; Vankayalapati, Hariprasad.

Affiliation

Chen T; Department of Physiology & Developmental Biology, Brigham Young University, Provo, UT 84602, USA.
Sorna V; Division of Oncology of School of Medicine and Center for Investigational Therapeutics at Huntsman Cancer Institute, University of Utah, 2000 Circle of Hope, Salt Lake City, UT 84112, USA.
Choi S; Division of Oncology of School of Medicine and Center for Investigational Therapeutics at Huntsman Cancer Institute, University of Utah, 2000 Circle of Hope, Salt Lake City, UT 84112, USA.
Call L; Division of Oncology of School of Medicine and Center for Investigational Therapeutics at Huntsman Cancer Institute, University of Utah, 2000 Circle of Hope, Salt Lake City, UT 84112, USA.
Bearss J; Tolero Pharmaceuticals, Inc., 2975 Executive Parkway, Suite 320, Lehi, UT 84043, USA.
Carpenter K; Tolero Pharmaceuticals, Inc., 2975 Executive Parkway, Suite 320, Lehi, UT 84043, USA.
Warner SL; Tolero Pharmaceuticals, Inc., 2975 Executive Parkway, Suite 320, Lehi, UT 84043, USA.
Sharma S; Division of Oncology of School of Medicine and Center for Investigational Therapeutics at Huntsman Cancer Institute, University of Utah, 2000 Circle of Hope, Salt Lake City, UT 84112, USA.
Bearss DJ; Tolero Pharmaceuticals, Inc., 2975 Executive Parkway, Suite 320, Lehi, UT 84043, USA. Electronic address: dbearss@toleropharma.com.
Vankayalapati H; Division of Oncology of School of Medicine and Center for Investigational Therapeutics at Huntsman Cancer Institute, University of Utah, 2000 Circle of Hope, Salt Lake City, UT 84112, USA. Electronic address: hari@hci.utah.edu.

Bioorg Med Chem Lett ; 27(24): 5473-5480, 2017 12 15.

Article in En | MEDLINE | ID: mdl-29150397

Subject(s)

Drug Design; Indazoles/chemistry; Protein Kinase Inhibitors/chemical synthesis; Protein Serine-Threonine Kinases/antagonists & inhibitors; Apoptosis/drug effects; Binding Sites; Cell Line, Tumor; Down-Regulation/drug effects; Dual Specificity Phosphatase 6/genetics; Dual Specificity Phosphatase 6/metabolism; Dual-Specificity Phosphatases/genetics; Dual-Specificity Phosphatases/metabolism; Humans; Imidazoles/chemistry; Indazoles/chemical synthesis; Indazoles/pharmacology; Inhibitory Concentration 50; Mitogen-Activated Protein Kinase Phosphatases/genetics; Mitogen-Activated Protein Kinase Phosphatases/metabolism; Molecular Docking Simulation; PTEN Phosphohydrolase/antagonists & inhibitors; PTEN Phosphohydrolase/genetics; PTEN Phosphohydrolase/metabolism; Phosphorylation/drug effects; Protein Kinase Inhibitors/chemistry; Protein Kinase Inhibitors/pharmacology; Protein Serine-Threonine Kinases/metabolism; Proto-Oncogene Proteins c-akt/metabolism; Pyruvate Dehydrogenase Acetyl-Transferring Kinase; RNA Interference; RNA, Small Interfering/metabolism; Ribosomal Protein S6 Kinases, 70-kDa/metabolism; Structure-Activity Relationship

Key words

1H-benzo[d]imidazol-2-yl)-1H-indazoles; AN3-CA; DUSP4; DUSP6; FOSL1; Fragment-based design; KATO-III; MV4-11; PDK1 inhibitor

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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Drug Design / Protein Serine-Threonine Kinases / Protein Kinase Inhibitors / Indazoles Limits: Humans Language: En Journal: Bioorg Med Chem Lett Journal subject: BIOQUIMICA / QUIMICA Year: 2017 Type: Article Affiliation country: United States

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