Browse views: by Year, by Function, by GLF, by Subfunction, by Conference, by Journal

Identification of N-(4-((1R,3S,5S)-3-amino-5-methylcyclohexyl)pyridin-3-yl)-6-(2,6-difluorophenyl)-5-fluoropicolinamide (PIM447), a Potent and Selective Proviral Insertion Site of Moloney Murine Leukemia (PIM) 1,2 and 3 Kinase Inhibitor in Clinical Trials for Hematological Malignancies

Burger, Matthew and Nishiguchi, Gisele and Han, Wooseok and Lan, Jiong and Simmons, Bob and Atallah, Gordana and Ding, Yu and Tamez Jr., Victoriano and zhang, yanchen and mathur, michelle and muller, kristine and Bellamacina, Cornelia and Lindvall, Mika and Zang, Richard and Huh, Kay and Feucht, Paul and Zavorotinskaya, Tatiana and Dai, Yumin and Basham, Steve and Chan, Julie and Ginn, Elaine and Aycinena, Alex and Holash, Jocelyn and Castillo, Joseph and Langowski, John and Wang, Yingyun and Chen, Min and Lambert, Amy and Fritsch, Christine and Kauffmann, Audrey and Pfister-Wagner, Estelle and Vanasse, K. Gary and Garcia, Pablo (2015) Identification of N-(4-((1R,3S,5S)-3-amino-5-methylcyclohexyl)pyridin-3-yl)-6-(2,6-difluorophenyl)-5-fluoropicolinamide (PIM447), a Potent and Selective Proviral Insertion Site of Moloney Murine Leukemia (PIM) 1,2 and 3 Kinase Inhibitor in Clinical Trials for Hematological Malignancies. Journal of Medicinal Chemistry.

Abstract

Pan Proviral Insertion Site of Moloney Murine Leukemia (PIM) 1, 2 and 3 kinase inhibitors have recently begun to be tested in humans to assess whether pan PIM kinase inhibition may provide benefit to cancer patients. Herein, the synthesis, in vitro activity, in vivo activity in an acute myeloid leukemia xenograft model and pre-clinical profile of the potent and selective pan PIM kinase inhibitor 8 (PIM447) are described. Starting from the reported aminopiperidyl pan PIM kinase inhibitor 1, a strategy to improve the microsomal stability was pursued resulting in the identification of potent aminocyclohexyl pan PIM inhibitors with high metabolic stability. From this aminocyclohexyl series, 8 entered the clinic in 2012 in multiple myeloma patients and is currently in several phase 1 trials of cancer patients with hematological malignancies.

Item Type: Article
Date Deposited: 18 Dec 2015 00:45
Last Modified: 18 Dec 2015 00:45
URI: https://oak.novartis.com/id/eprint/26675

Search

Email Alerts

Register with OAK to receive email alerts for saved searches.