Identification and Optimization of cell active 4-anilino-quin(az)oline Inhibitors for Protein Kinase Novel 3 (PKN3)

C. R. M. Asquith; L. Temme; T. Laitinen; J. Pickett; F. E. Kwarcinski; P. Sinha; C. I. Wells; G. J. Tizzard; R. Zutshi; D. H. Drewry

doi:10.1101/2020.03.02.972943

Pharmacology & ToxicologybioRxivMar 2, 2020

Preprint

Identification and Optimization of cell active 4-anilino-quin(az)oline Inhibitors for Protein Kinase Novel 3 (PKN3)

C. R. M. Asquith, L. Temme, T. Laitinen, J. Pickett, F. E. Kwarcinski, P. Sinha, C. I. Wells, G. J. Tizzard, R. Zutshi, D. H. Drewry

Abstract

The development of a small library of 4-anilinoquinolines led to the identification of 7-iodo-N-(3,4,5-trimethoxyphenyl)quinolin-4-amine 16 as a potent inhibitor of Protein Kinase Novel 3 (PKN3) with an IC50 of 1.3 M in cells. Compound 16 presents a useful potential tool compound to study the biology of PKN3 including links to pancreatic and prostate cancer, along with T-cell acute lymphoblastic leukemia. These compounds may be useful tools to explore the therapeutic potential of PKN3 inhibition in prevention of a broad range of infectious and systemic diseases.

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