Indolinone based phosphoinositide-dependent kinase-1 (PDK1) inhibitors. Part 1: Design, synthesis and biological activity.

Imadul Islam,Judi Bryant,Yuo-Ling Chou,Monica J. Kochanny,Wheeseong Lee,Gary Phillips,Hongyi Yu,Marc Adler,Marc Whitlow,Elena Ho,Dao Lentz,Mark Polokoff,Babu Subramanyam,James Wu,Daguang Zhu,Richard I. Feldman,Damian O. Arnaiz

Indolinone based phosphoinositide-dependent kinase-1 (PDK1) inhibitors. Part 1: Design, synthesis and biological activity.

2007

Imadul Islam
Judi Bryant
Yuo-Ling Chou
Monica J. Kochanny
Wheeseong Lee
Gary Phillips
Hongyi Yu
Marc Adler
Marc Whitlow
Elena Ho
Dao Lentz
Mark Polokoff
Babu Subramanyam
James Wu
Daguang Zhu
Richard I. Feldman
Damian O. Arnaiz

HTS screening identified 1 with micromolar inhibitory activity against PDK1. Optimization of 1 afforded 4i (BX-517) which has single-digit nanomolar activity against PDK1 and excellent selectivity against PKA.

Keywords:

Protein kinase A
Enzyme
Protein kinase B
Organic chemistry
Signal transduction
Biological activity
Biochemistry
Chemistry
Enzyme inhibitor
Phosphoinositide-dependent kinase-1
Transferase
Chemical synthesis

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