Literature DB >> 24900437

Discovery of CX-6258. A Potent, Selective, and Orally Efficacious pan-Pim Kinases Inhibitor.

Mustapha Haddach1, Jerome Michaux1, Michael K Schwaebe1, Fabrice Pierre1, Sean E O'Brien1, Cosmin Borsan1, Joe Tran1, Nicholas Raffaele1, Suchitra Ravula1, Denis Drygin1, Adam Siddiqui-Jain1, Levan Darjania1, Ryan Stansfield1, Chris Proffitt1, Diwata Macalino1, Nicole Streiner1, Joshua Bliesath1, May Omori1, Jeffrey P Whitten1, Kenna Anderes1, William G Rice1, David M Ryckman1.   

Abstract

Structure-activity relationship analysis in a series of 3-(5-((2-oxoindolin-3-ylidene)methyl)furan-2-yl)amides identified compound 13, a pan-Pim kinases inhibitor with excellent biochemical potency and kinase selectivity. Compound 13 exhibited in vitro synergy with chemotherapeutics and robust in vivo efficacy in two Pim kinases driven tumor models.

Entities:  

Keywords:  CX-6258; MV-4-11; PC3; Pim-1; Pim-2; Pim-3

Year:  2011        PMID： 24900437      PMCID： PMC4025662          DOI： 10.1021/ml200259q

Source DB:  PubMed          Journal:  ACS Med Chem Lett        ISSN： 1948-5875            Impact factor:   4.345


  35 in total

1.  The oncogenic serine/threonine kinase Pim-1 directly phosphorylates and activates the G2/M specific phosphatase Cdc25C.

Authors:  Malte Bachmann; Christian Kosan; Pei Xiang Xing; Mathias Montenarh; Ingrid Hoffmann; Tarik Möröy
Journal:  Int J Biochem Cell Biol       Date:  2005-11-08       Impact factor: 5.085

2.  Identification and structure-activity relationships of substituted pyridones as inhibitors of Pim-1 kinase.

Authors:  I Wayne Cheney; Shunqi Yan; Todd Appleby; Heli Walker; Todd Vo; Nanhua Yao; Robert Hamatake; Zhi Hong; Jim Z Wu
Journal:  Bioorg Med Chem Lett       Date:  2007-01-04       Impact factor: 2.823

3.  Discovery of novel 3,5-disubstituted indole derivatives as potent inhibitors of Pim-1, Pim-2, and Pim-3 protein kinases.

Authors:  Gisele A Nishiguchi; Gordana Atallah; Cornelia Bellamacina; Matthew T Burger; Yu Ding; Paul H Feucht; Pablo D Garcia; Wooseok Han; Liana Klivansky; Mika Lindvall
Journal:  Bioorg Med Chem Lett       Date:  2011-09-10       Impact factor: 2.823

4.  Developmental expression of pim kinases suggests functions also outside of the hematopoietic system.

Authors:  A Eichmann; L Yuan; C Bréant; K Alitalo; P J Koskinen
Journal:  Oncogene       Date:  2000-02-24       Impact factor: 9.867

5.  Physical and functional interactions between Pim-1 kinase and Cdc25A phosphatase. Implications for the Pim-1-mediated activation of the c-Myc signaling pathway.

Authors:  T Mochizuki; C Kitanaka; K Noguchi; T Muramatsu; A Asai; Y Kuchino
Journal:  J Biol Chem       Date:  1999-06-25       Impact factor: 5.157

6.  Aberrant Pim-3 expression is involved in gastric adenoma-adenocarcinoma sequence and cancer progression.

Authors:  Hua-Chuan Zheng; Koichi Tsuneyama; Hiroyuki Takahashi; Shigeharu Miwa; Toshiro Sugiyama; Boryana Konstantinova Popivanova; Chifumi Fujii; Kazuhiro Nomoto; Naofumi Mukaida; Yasuo Takano
Journal:  J Cancer Res Clin Oncol       Date:  2007-09-18       Impact factor: 4.553

7.  Transcriptional induction of pim-1 protein kinase gene expression by interferon gamma and posttranscriptional effects on costimulation with steel factor.

Authors:  M T Yip-Schneider; M Horie; H E Broxmeyer
Journal:  Blood       Date:  1995-06-15       Impact factor: 22.113

8.  E mu N- and E mu L-myc cooperate with E mu pim-1 to generate lymphoid tumors at high frequency in double-transgenic mice.

Authors:  T Möröy; S Verbeek; A Ma; P Achacoso; A Berns; F Alt
Journal:  Oncogene       Date:  1991-11       Impact factor: 9.867

9.  Pim kinase-dependent inhibition of c-Myc degradation.

Authors:  Y Zhang; Z Wang; X Li; N S Magnuson
Journal:  Oncogene       Date:  2008-04-28       Impact factor: 9.867

10.  Proviral activation of the putative oncogene Pim-1 in MuLV induced T-cell lymphomas.

Authors:  G Selten; H T Cuypers; A Berns
Journal:  EMBO J       Date:  1985-07       Impact factor: 11.598
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  20 in total

1.  Inhibition of oncogenic Pim-3 kinase modulates transformed growth and chemosensitizes pancreatic cancer cells to gemcitabine.

Authors:  Dapeng Xu; Michael G Cobb; Lily Gavilano; Sam M Witherspoon; Daniel Williams; Catherine D White; Pietro Taverna; Brian K Bednarski; Hong Jin Kim; Albert S Baldwin; Antonio T Baines
Journal:  Cancer Biol Ther       Date:  2013-06       Impact factor: 4.742

2.  Protein profiling identifies mTOR pathway modulation and cytostatic effects of Pim kinase inhibitor, AZD1208, in acute myeloid leukemia.

Authors:  Lisa S Chen; Ji-Yeon Yang; Han Liang; Jorge E Cortes; Varsha Gandhi
Journal:  Leuk Lymphoma       Date:  2016-04-07

3.  Characterization of HJ-PI01 as a novel Pim-2 inhibitor that induces apoptosis and autophagic cell death in triple-negative human breast cancer.

Authors:  Yu-Qian Zhao; Yi-Qiong Yin; Jie Liu; Gui-Hua Wang; Jian Huang; Ling-Juan Zhu; Jin-Hui Wang
Journal:  Acta Pharmacol Sin       Date:  2016-07-11       Impact factor: 6.150

4.  Pan-PIM kinase inhibitors enhance Lenalidomide's anti-myeloma activity via cereblon-IKZF1/3 cascade.

Authors:  Jing Zheng; Yonggang Sha; Logan Roof; Oded Foreman; John Lazarchick; Jagadish Kummetha Venkta; Cleopatra Kozlowski; Cristina Gasparetto; Nelson Chao; Allen Ebens; Jianda Hu; Yubin Kang
Journal:  Cancer Lett       Date:  2018-10-09       Impact factor: 8.679

Review 5.  PIM kinase inhibition: co-targeted therapeutic approaches in prostate cancer.

Authors:  Sabina Luszczak; Christopher Kumar; Vignesh Krishna Sathyadevan; Benjamin S Simpson; Kathy A Gately; Hayley C Whitaker; Susan Heavey
Journal:  Signal Transduct Target Ther       Date:  2020-01-31

6.  Structure Guided Optimization, in Vitro Activity, and in Vivo Activity of Pan-PIM Kinase Inhibitors.

Authors:  Matthew T Burger; Wooseok Han; Jiong Lan; Gisele Nishiguchi; Cornelia Bellamacina; Mika Lindval; Gordana Atallah; Yu Ding; Michelle Mathur; Chris McBride; Elizabeth L Beans; Kristine Muller; Victoriano Tamez; Yanchen Zhang; Kay Huh; Paul Feucht; Tatiana Zavorotinskaya; Yumin Dai; Jocelyn Holash; Joseph Castillo; John Langowski; Yingyun Wang; Min Y Chen; Pablo D Garcia
Journal:  ACS Med Chem Lett       Date:  2013-10-15       Impact factor: 4.345

7.  Synthesis of 3-(3-aryl-pyrrolidin-1-yl)-5-aryl-1,2,4-triazines that have antibacterial activity and also inhibit inorganic pyrophosphatase.

Authors:  Wei Lv; Biplab Banerjee; Katrina L Molland; Mohamed N Seleem; Adil Ghafoor; Maha I Hamed; Baojie Wan; Scott G Franzblau; Andrew D Mesecar; Mark Cushman
Journal:  Bioorg Med Chem       Date:  2013-11-15       Impact factor: 3.641

8.  Inhibition of Haspin Kinase Promotes Cell-Intrinsic and Extrinsic Antitumor Activity.

Authors:  Johannes C Melms; Sreeram Vallabhaneni; Caitlin E Mills; Clarence Yapp; Jia-Yun Chen; Eugenio Morelli; Patricia Waszyk; Sushil Kumar; Derrick Deming; Nienke Moret; Steven Rodriguez; Kartik Subramanian; Meri Rogava; Adam N R Cartwright; Adrienne Luoma; Shaolin Mei; Titus J Brinker; David M Miller; Alexander Spektor; Dirk Schadendorf; Nicolo Riggi; Kai W Wucherpfennig; Peter K Sorger; Benjamin Izar
Journal:  Cancer Res       Date:  2019-12-27       Impact factor: 12.701

9.  Computational prediction and experimental validation of a novel synthesized pan-PIM inhibitor PI003 and its apoptosis-inducing mechanisms in cervical cancer.

Authors:  Zhongyu Liu; Weihua He; Jianglin Gao; Junhua Luo; Xian Huang; Chunfang Gao
Journal:  Oncotarget       Date:  2015-04-10

10.  Structural analysis of PIM1 kinase complexes with ATP-competitive inhibitors.

Authors:  Jozefina Bogusz; Karol Zrubek; Krzysztof P Rembacz; Przemyslaw Grudnik; Przemyslaw Golik; Malgorzata Romanowska; Benedykt Wladyka; Grzegorz Dubin
Journal:  Sci Rep       Date:  2017-10-17       Impact factor: 4.379
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