Identification of 4-Anilinoquin(az)oline as a Cell-Active Protein Kinase Novel 3 (PKN3) Inhibitor Chemotype

  • ChemMedChem. 2022 Jun 20;17(12):e202200161. doi: 10.1002/cmdc.202200161.
Christopher R M Asquith  1  2 ,  Louisa Temme  1 ,  Michael P East  2 ,  Tuomo Laitinen  3 ,  Julie Pickett  1 ,  Frank E Kwarcinski  4 ,  Parvathi Sinha  4 ,  Carrow I Wells  1 ,  Gary L Johnson  2  5 ,  Reena Zutshi  4 ,  David H Drewry  1  5
Affiliations
  • 1. Structural Genomics Consortium UNC Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
  • 2. Department of Pharmacology School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
  • 3. School of Pharmacy Faculty of Health Sciences, University of Eastern Finland, 70211, Kuopio, Finland.
  • 4. Luceome Biotechnologies, LLC, Tucson, AZ 85719, USA.
  • 5. Lineberger Comprehensive Cancer Center School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
PMID: 35403825 DOI: 10.1002/cmdc.202200161
Abstract

Deep annotation of a library of 4-anilinoquin(az)olines led to the identification of 7-iodo-N-(3,4,5-trimethoxyphenyl)quinolin-4-amine 16 as a potent inhibitor (IC50 =14 nM) of Protein Kinase Novel 3 (PKN3) with micromolar activity in cells. Compound 16 is a potential tool compound to study the Cell Biology of PKN3 and its role in pancreatic and prostate Cancer and T-cell acute lymphoblastic leukemia. These 4-anilinoquin(az)olines may also be useful tools to uncover the therapeutic potential of PKN3 inhibition in a broad range of diseases.

Keywords
4-anilinoquinazoline; 4-anilinoquinoline; Protein Kinase Novel 3 (PKN3); homology model.
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