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

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

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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