Nonacidic Inhibitors of Human Microsomal Prostaglandin Synthase 1 (mPGES 1) Identified by a Multistep Virtual Screening Protocol

被引：33
|
作者：
Roersch, Florian [1 ]
Wobst, Ivonne [3 ]
Zettl, Heiko [2 ]
Schubert-Zsilavecz, Manfred [2 ]
Groesch, Sabine [3 ]
Geisslinger, Gerd [3 ]
Schneider, Gisbert [1 ]
Proschak, Ewgenij [1 ]
机构：
[1] Goethe Univ Frankfurt, Inst Organ Chem & Chem Biol, LiFF ZAFES, D-60323 Frankfurt, Germany
[2] Goethe Univ Frankfurt, Inst Pharmaceut Chem, LiFF ZAFES, D-60438 Frankfurt, Germany
[3] Goethe Univ Frankfurt, Inst Clin Pharmacol, Pharmazentrum Frankfurt, LiFF ZAFES, D-60590 Frankfurt, Germany
来源：
JOURNAL OF MEDICINAL CHEMISTRY | 2010年 / 53卷 / 02期
关键词：
RANDOMIZED CONTROLLED-TRIAL; SELF-ORGANIZING MAPS; RHEUMATOID-ARTHRITIS; THERAPEUTIC TARGET; E-2; SYNTHASE-1; CYCLOOXYGENASE-2; PHARMACOPHORES; ANTAGONISTS; CELECOXIB; DESIGN;
D O I：
10.1021/jm9012505
中图分类号：
R914 [药物化学];
学科分类号：
100701 ;
摘要：
Microsomal prostaglandin E-2-synthase (mPGES-1) is a target for future anti-inflammatory drugs. Inhibitors of mPGES-1 mimicking prostaglandin E-2 often interact with cyclooxygenases (COXs) 1 and 2, leading to unwanted side effects. Selective inhibitors of mPGES-1 can be obtained by deliberate abdication of the acidic groups, which are an important feature of COX inhibition. Here, we present it Successful virtual screening study that results in it potent nonacidic mPGES-1 inhibitor lacking COX Inhibition.
引用
收藏
页码：911 / 915
页数：5
相关论文
共 50 条
  • [1] Structure-Activity Relationship of Nonacidic Quinazolinone Inhibitors of Human Microsomal Prostaglandin Synthase 1 (mPGES 1)
    Roersch, Florian
    La Buscato, Estel.
    Deckmann, Klaus
    Schneider, Gisbert
    Schubert-Zsilavecz, Manfred
    Geisslinger, Gerd
    Proschak, Ewgenij
    Groesch, Sabine
    JOURNAL OF MEDICINAL CHEMISTRY, 2012, 55 (08) : 3792 - 3803
  • [2] Virtual screening, molecular simulations and bioassays: Discovering novel microsomal prostaglandin E Synthase-1 (mPGES-1) inhibitors
    Babaoglu, Zeynep Yagmur
    Kilic, Deryanur
    COMPUTERS IN BIOLOGY AND MEDICINE, 2023, 155
  • [3] Discovery of novel microsomal prostaglandin E2 synthase 1 (mPGES-1) inhibitors by a structurally inspired virtual screening study
    Olgac, Abdurrahman
    Jordan, Paul M.
    Kretzer, Christian
    Werz, Oliver
    Banoglu, Erden
    JOURNAL OF MOLECULAR GRAPHICS & MODELLING, 2025, 136
  • [4] Pharmacophore Modeling and Virtual Screening for Novel Acidic Inhibitors of Microsomal Prostaglandin E2 Synthase-1 (mPGES-1)
    Waltenberger, Birgit
    Wiechmann, Katja
    Bauer, Julia
    Markt, Patrick
    Noha, Stefan M.
    Wolber, Gerhard
    Rollinger, Judith M.
    Werz, Oliver
    Schuster, Daniela
    Stuppner, Hermann
    JOURNAL OF MEDICINAL CHEMISTRY, 2011, 54 (09) : 3163 - 3174
  • [5] Identification of novel microsomal prostaglandin E2 synthase-1 (mPGES-1) lead inhibitors from Fragment Virtual Screening
    Lauro, Gianluigi
    Manfra, Michele
    Pedatella, Silvana
    Fischer, Katrin
    Cantone, Vincenza
    Terracciano, Stefania
    Bertamino, Alessia
    Ostacolo, Carmine
    Gomez-Monterrey, Isabel
    De Nisco, Mauro
    Riccio, Raffaele
    Novellino, Ettore
    Werz, Oliver
    Campiglia, Pietro
    Bifulco, Giuseppe
    EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, 2017, 125 : 278 - 287
  • [6] Development of microsomal prostaglandin E2 Synthase 1 (mPGES-1) inhibitors
    Roersch, F.
    Buscato, E.
    Deckmann, K.
    Schneider, G.
    Geisslinger, G.
    Steinhilber, D.
    Proschak, E.
    Groesch, S.
    NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY, 2011, 383 : 75 - 76
  • [7] Discovery of novel, non-acidic mPGES-1 inhibitors by virtual screening with a multistep protocol
    Noha, Stefan M.
    Fischer, Katrin
    Koeberle, Andreas
    Garscha, Ulrike
    Werz, Oliver
    Schuster, Daniela
    BIOORGANIC & MEDICINAL CHEMISTRY, 2015, 23 (15) : 4839 - 4845
  • [8] A Multi-step Virtual Screening Protocol for the Identification of Novel Non-acidic Microsomal Prostaglandin E2 Synthase-1 (mPGES-1) Inhibitors
    Shekfeh, Suhaib
    Caliskan, Burcu
    Fischer, Katrin
    Yalcin, Tansu
    Garscha, Ulrike
    Werz, Oliver
    Banoglu, Erden
    CHEMMEDCHEM, 2019, 14 (02) : 273 - 281
  • [9] HQSAR study of microsomal prostaglandin E2 synthase (mPGES-1) inhibitors
    San Juan, Amor A.
    Cho, Seung Joo
    Cho, Hoon
    BULLETIN OF THE KOREAN CHEMICAL SOCIETY, 2006, 27 (10) : 1531 - 1536
  • [10] Novel human mPGES-1 inhibitors identified through structure-based virtual screening
    Hamza, Adel
    Zhao, Xinyun
    Tong, Min
    Tai, Hsin-Hsiung
    Zhan, Chang-Guo
    BIOORGANIC & MEDICINAL CHEMISTRY, 2011, 19 (20) : 6077 - 6086
12345