Literature DB >> 19309081

Pyranonaphthoquinone lactones: a new class of AKT selective kinase inhibitors alkylate a regulatory loop cysteine.

Edward J Salaski1, Girija Krishnamurthy, Wei-Dong Ding, Ker Yu, Shabana S Insaf, Clark Eid, Jaechul Shim, Jeremy I Levin, Keiko Tabei, Lourdes Toral-Barza, Wei-Guo Zhang, Leonard A McDonald, Erick Honores, Cilien Hanna, Ayako Yamashita, Bernard Johnson, Zhong Li, Leif Laakso, Dennis Powell, Tarek S Mansour.   

Abstract

The naturally occurring pyranonaphthoquinone (PNQ) antibiotic lactoquinomycin and related aglycones were found to be selective inhibitors of the serine-threonine kinase AKT. A set of synthetic PNQs were prepared and a minimum active feature set and preliminary SAR were determined. PNQ lactones inhibit the proliferation of human tumor cell lines containing constitutively activated AKT and show expected effects on cellular biomarkers. Biochemical data are presented supporting a proposed bioreductive alkylation mechanism of action.

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Year:  2009        PMID： 19309081     DOI： 10.1021/jm900075g

Source DB:  PubMed          Journal:  J Med Chem        ISSN： 0022-2623            Impact factor:   7.446


  17 in total

1.  Akt Cys-310-targeted inhibition by hydroxylated benzene derivatives is tightly linked to their immunosuppressive effects.

Authors:  Ji Yeon Lee; Yong Gyu Lee; Jaehwi Lee; Keum-Jin Yang; Ae Ra Kim; Joo Young Kim; Moo-Ho Won; Jongsun Park; Byong Chul Yoo; Sanghee Kim; Won-Jea Cho; Jae Youl Cho
Journal:  J Biol Chem       Date:  2010-01-06       Impact factor: 5.157

2.  Xiakemycin A, a novel pyranonaphthoquinone antibiotic, produced by the Streptomyces sp. CC8-201 from the soil of a karst cave.

Authors:  Zhong-ke Jiang; Lin Guo; Chuan Chen; Shao-wei Liu; Lin Zhang; Su-juan Dai; Qi-yang He; Xue-fu You; Xin-xin Hu; Li Tuo; Wei Jiang; Cheng-hang Sun
Journal:  J Antibiot (Tokyo)       Date:  2015-06-24       Impact factor: 2.649

3.  Cycloadditions of Oxacyclic Allenes and a Catalytic Asymmetric Entryway to Enantioenriched Cyclic Allenes.

Authors:  Michael M Yamano; Rachel R Knapp; Aurapat Ngamnithiporn; Melissa Ramirez; Kendall N Houk; Brian M Stoltz; Neil K Garg
Journal:  Angew Chem Int Ed Engl       Date:  2019-03-20       Impact factor: 15.336

4.  Exploitation of the ability of γ-tocopherol to facilitate membrane co-localization of Akt and PHLPP1 to develop PHLPP1-targeted Akt inhibitors.

Authors:  Ribai Yan; Hsiao-Ching Chuang; Naval Kapuriya; Chih-Chien Chou; Po-Ting Lai; Hsin-Wen Chang; Chia-Ning Yang; Samuel K Kulp; Ching-Shih Chen
Journal:  J Med Chem       Date:  2015-02-27       Impact factor: 7.446

5.  Expanding the Strained Alkyne Toolbox: Generation and Utility of Oxygen-Containing Strained Alkynes.

Authors:  Tejas K Shah; Jose M Medina; Neil K Garg
Journal:  J Am Chem Soc       Date:  2016-03-29       Impact factor: 15.419

6.  Phenylalanine-Based Inactivator of AKT Kinase: Design, Synthesis, and Biological Evaluation.

Authors:  Thuy Nguyen; Robert A Coover; Jenson Verghese; Richard G Moran; Keith C Ellis
Journal:  ACS Med Chem Lett       Date:  2014-03-07       Impact factor: 4.345

7.  A diastereoselective oxa-Pictet-Spengler-based strategy for (+)-frenolicin B and epi-(+)-frenolicin B synthesis.

Authors:  Yinan Zhang; Xiachang Wang; Manjula Sunkara; Qing Ye; Larissa V Ponomereva; Qing-Bai She; Andrew J Morris; Jon S Thorson
Journal:  Org Lett       Date:  2013-10-23       Impact factor: 6.005

Review 8.  Recent development of anticancer therapeutics targeting Akt.

Authors:  John K Morrow; Lei Du-Cuny; Lu Chen; Emmanuelle J Meuillet; Eugene A Mash; Garth Powis; Shuxing Zhang
Journal:  Recent Pat Anticancer Drug Discov       Date:  2011-01       Impact factor: 4.169

9.  Ruthmycin, a new tetracyclic polyketide from Streptomyces sp. RM-4-15.

Authors:  Xiachang Wang; Sherif I Elshahawi; Khaled A Shaaban; Lei Fang; Larissa V Ponomareva; Yinan Zhang; Gregory C Copley; James C Hower; Chang-Guo Zhan; Madan K Kharel; Jon S Thorson
Journal:  Org Lett       Date:  2013-12-16       Impact factor: 6.005

10.  Expression, Crystallization and Preliminary X-ray Diffraction Analyses of Med-ORF10 in the Biosynthetic Pathway of an Antitumor Antibiotic Medermycin.

Authors:  Yanli Liu; Shasha Liu; Tingting Yang; Xiaoxia Guo; Yali Jiang; Kashif Rafiq Zahid; Ke Liu; Jinlin Liu; Jihong Yang; Haobin Zhao; Yi Yang; Aiying Li; Chao Qi
Journal:  Protein J       Date:  2015-12       Impact factor: 2.371
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