Literature DB >> 20951039

Synthesis and structure-activity relationships of tyrosine-based inhibitors of autotaxin (ATX).

James E East1, Andrew J Kennedy, Jose L Tomsig, Alexandra R De Leon, Kevin R Lynch, Timothy L Macdonald.   

Abstract

Autotaxin (ATX) is a secreted soluble enzyme that generates lysophosphatidic acid (LPA) through its lysophospholipase D activity. Because of LPA's role in neoplastic diseases, ATX is an attractive therapeutic target due to its involvement in LPA biosynthesis. Here we describe the SAR of ATX inhibitor, VPC8a202, and apply this SAR knowledge towards developing a high potency inhibitor. We found that electron density in the pyridine region greatly influences activity of our inhibitors at ATX.
Copyright © 2010 Elsevier Ltd. All rights reserved.

Entities:  

Mesh：

Substances：

Year:  2010        PMID： 20951039      PMCID： PMC2975792          DOI： 10.1016/j.bmcl.2010.09.030

Source DB:  PubMed          Journal:  Bioorg Med Chem Lett        ISSN： 0960-894X            Impact factor:   2.823


  18 in total

1.  Fast calculation of molecular polar surface area as a sum of fragment-based contributions and its application to the prediction of drug transport properties.

Authors:  P Ertl; B Rohde; P Selzer
Journal:  J Med Chem       Date:  2000-10-05       Impact factor: 7.446

2.  Discovery and optimization of boronic acid based inhibitors of autotaxin.

Authors:  Harald M H G Albers; Laurens A van Meeteren; David A Egan; Erica W van Tilburg; Wouter H Moolenaar; Huib Ovaa
Journal:  J Med Chem       Date:  2010-07-08       Impact factor: 7.446

3.  Initial structure-activity relationships of lysophosphatidic acid receptor antagonists: discovery of a high-affinity LPA1/LPA3 receptor antagonist.

Authors:  Brian H Heasley; Renata Jarosz; Kevin R Lynch; Timothy L Macdonald
Journal:  Bioorg Med Chem Lett       Date:  2004-06-07       Impact factor: 2.823

4.  Structural and functional comparisons of nucleotide pyrophosphatase/phosphodiesterase and alkaline phosphatase: implications for mechanism and evolution.

Authors:  Jesse G Zalatan; Timothy D Fenn; Axel T Brunger; Daniel Herschlag
Journal:  Biochemistry       Date:  2006-08-15       Impact factor: 3.162

5.  Characterization of a receptor subtype-selective lysophosphatidic acid mimetic.

Authors:  S B Hooks; S P Ragan; D W Hopper; C W Hönemann; M E Durieux; T L Macdonald; K R Lynch
Journal:  Mol Pharmacol       Date:  1998-02       Impact factor: 4.436

6.  Quantitative structure-activity relationships of antimalarial and dihydrofolate reductase inhibition by quinazolines and 5-substituted benzyl-2,4-diaminopyrimidines.

Authors:  C Hansch; J Y Fukunaga; P Y Jow
Journal:  J Med Chem       Date:  1977-01       Impact factor: 7.446

7.  Inhibition of autotaxin by lysophosphatidic acid and sphingosine 1-phosphate.

Authors:  Laurens A van Meeteren; Paula Ruurs; Evangelos Christodoulou; James W Goding; Hideo Takakusa; Kazuya Kikuchi; Anastassis Perrakis; Tetsuo Nagano; Wouter H Moolenaar
Journal:  J Biol Chem       Date:  2005-03-15       Impact factor: 5.157

8.  Synthesis and biological evaluation of phosphonic and thiophosphoric acid derivatives of lysophosphatidic acid.

Authors:  Webster L Santos; Brian H Heasley; Renata Jarosz; Karen M Carter; Kevin R Lynch; Timothy L Macdonald
Journal:  Bioorg Med Chem Lett       Date:  2004-07-05       Impact factor: 2.823

9.  A novel series of 2-pyridyl-containing compounds as lysophosphatidic acid receptor antagonists: development of a nonhydrolyzable LPA3 receptor-selective antagonist.

Authors:  Brian H Heasley; Renata Jarosz; Karen M Carter; S Jenny Van; Kevin R Lynch; Timothy L Macdonald
Journal:  Bioorg Med Chem Lett       Date:  2004-08-02       Impact factor: 2.823

10.  Identification, purification, and partial sequence analysis of autotaxin, a novel motility-stimulating protein.

Authors:  M L Stracke; H C Krutzsch; E J Unsworth; A Arestad; V Cioce; E Schiffmann; L A Liotta
Journal:  J Biol Chem       Date:  1992-02-05       Impact factor: 5.157
View more
  8 in total

Review 1.  Regulation of mammalian physiology, development, and disease by the sphingosine 1-phosphate and lysophosphatidic acid receptors.

Authors:  Victoria A Blaho; Timothy Hla
Journal:  Chem Rev       Date:  2011-09-22       Impact factor: 60.622

2.  Vinyl sulfone analogs of lysophosphatidylcholine irreversibly inhibit autotaxin and prevent angiogenesis in melanoma.

Authors:  Mandi M Murph; Guowei W Jiang; Molly K Altman; Wei Jia; Duy T Nguyen; Jada M Fambrough; William J Hardman; Ha T Nguyen; Sterling K Tran; Ali A Alshamrani; Damian Madan; Jianxing Zhang; Glenn D Prestwich
Journal:  Bioorg Med Chem       Date:  2015-07-02       Impact factor: 3.641

Review 3.  Autotaxin, a lysophospholipase D with pleomorphic effects in oncogenesis and cancer progression.

Authors:  Lorenzo Federico; Kang Jin Jeong; Christopher P Vellano; Gordon B Mills
Journal:  J Lipid Res       Date:  2015-05-14       Impact factor: 5.922

4.  Regulation of autotaxin expression and secretion by lysophosphatidate and sphingosine 1-phosphate.

Authors:  Matthew G K Benesch; Yuan Y Zhao; Jonathan M Curtis; Todd P W McMullen; David N Brindley
Journal:  J Lipid Res       Date:  2015-04-20       Impact factor: 5.922

5.  Autotaxin is induced by TSA through HDAC3 and HDAC7 inhibition and antagonizes the TSA-induced cell apoptosis.

Authors:  Song Li; Baolu Wang; Yan Xu; Junjie Zhang
Journal:  Mol Cancer       Date:  2011-02-12       Impact factor: 27.401

6.  Pyrrolidine and oxazolidine ring transformations in proline and serine derivatives of α-hydroxyphosphonates induced by deoxyfluorinating reagents.

Authors:  Patrycja Kaczmarek; Magdalena Rapp; Henryk Koroniak
Journal:  RSC Adv       Date:  2018-07-06       Impact factor: 4.036

7.  Mechanism of rapid elimination of lysophosphatidic acid and related lipids from the circulation of mice.

Authors:  Abdel K Salous; Manikandan Panchatcharam; Manjula Sunkara; Paul Mueller; Anping Dong; Yuhuan Wang; Gregory A Graf; Susan S Smyth; Andrew J Morris
Journal:  J Lipid Res       Date:  2013-08-15       Impact factor: 5.922

Review 8.  Chemical evolution of autotaxin inhibitors.

Authors:  Harald M H G Albers; Huib Ovaa
Journal:  Chem Rev       Date:  2012-02-15       Impact factor: 60.622
  8 in total

北京卡尤迪生物科技股份有限公司 © 2022-2023.