scholarly journals Pharmacophoric Site Identification and Inhibitor Design for Autotaxin

Molecules ◽  
2019 ◽  
Vol 24 (15) ◽  
pp. 2808 ◽  
Author(s):  
Myeong Hwi Lee ◽  
Dae-Yon Lee ◽  
Anand Balupuri ◽  
Jong-Woo Jeong ◽  
Nam Sook Kang
Keyword(s):  
Drug Target ◽  
Inflammatory Diseases ◽  
Binding Pocket ◽  
Potential Drug Target ◽  
Potential Drug ◽  
Water Networks ◽  
High Potency ◽  
Experimental Approaches ◽  
Inhibitory Activities ◽  
Site Identification

Autotaxin (ATX) is a potential drug target that is associated with inflammatory diseases and various cancers. In our previous studies, we have designed several inhibitors targeting ATX using computational and experimental approaches. Here, we have analyzed topological water networks (TWNs) in the binding pocket of ATX. TWN analysis revealed a pharmacophoric site inside the pocket. We designed and synthesized compounds considering the identified pharmacophoric site. Furthermore, we performed biological experiments to determine their ATX inhibitory activities. High potency of the designed compounds supports the predictions of the TWN analysis.

scholarly journals Structural and Biochemical Features of Eimeria tenella Dihydroorotate Dehydrogenase, a Potential Drug Target

Genes ◽  
2020 ◽  
Vol 11 (12) ◽  
pp. 1468
Author(s):  
Dan Sato ◽  
Endah Dwi Hartuti ◽  
Daniel Ken Inaoka ◽  
Takaya Sakura ◽  
Eri Amalia ◽  
...  
Keyword(s):  
Crystal Structures ◽  
Drug Target ◽  
De Novo ◽  
Binding Pocket ◽  
Severe Form ◽  
Eimeria Tenella ◽  
Potential Drug Target ◽  
Dihydroorotate Dehydrogenase ◽  
Potential Drug ◽  
De Novo Biosynthesis

Dihydroorotate dehydrogenase (DHODH) is a mitochondrial monotopic membrane protein that plays an essential role in the pyrimidine de novo biosynthesis and electron transport chain pathways. In Eimeria tenella, an intracellular apicomplexan parasite that causes the most severe form of chicken coccidiosis, the activity of pyrimidine salvage pathway at the intracellular stage is negligible and it relies on the pyrimidine de novo biosynthesis pathway. Therefore, the enzymes of the de novo pathway are considered potential drug target candidates for the design of compounds with activity against this parasite. Although, DHODHs from E. tenella (EtDHODH), Plasmodium falciparum (PfDHODH), and human (HsDHODH) show distinct sensitivities to classical DHODH inhibitors, in this paper, we identify ferulenol as a potent inhibitor of both EtDHODH and HsDHODH. Additionally, we report the crystal structures of EtDHODH and HsDHODH in the absence and presence of ferulenol. Comparison of these enzymes showed that despite similar overall structures, the EtDHODH has a long insertion in the N-terminal helix region that assumes a disordered configuration. In addition, the crystal structures revealed that the ferulenol binding pocket of EtDHODH is larger than that of HsDHODH. These differences can be explored to accelerate structure-based design of inhibitors specifically targeting EtDHODH.

The Prokaryotic FAD Synthetase Family: A Potential Drug Target

2013 ◽  
Vol 19 (14) ◽  
pp. 2637-2648 ◽  
Author(s):  
Ana Serrano ◽  
Patricia Ferreira ◽  
Marta Martinez-Julvez ◽  
Milagros Medina
Keyword(s):  
Drug Target ◽  
Potential Drug Target ◽  
Potential Drug

Bacterial Polyphosphate Kinases Revisited: Role in Pathogenesis and Therapeutic Potential

2019 ◽  
Vol 20 (3) ◽  
pp. 292-301 ◽  
Author(s):  
Lalit Kumar Gautam ◽  
Prince Sharma ◽  
Neena Capalash
Keyword(s):  
Drug Target ◽  
Bacterial Infections ◽  
Therapeutic Potential ◽  
Wide Distribution ◽  
Medical Community ◽  
Polyphosphate Kinase ◽  
Potential Drug Target ◽  
Potential Drug ◽  
Resistant Strains ◽  
Structural Aspects

Bacterial infections have always been an unrestrained challenge to the medical community due to the rise of multi-drug tolerant and resistant strains. Pioneering work on Escherichia coli polyphosphate kinase (PPK) by Arthur Kornberg has generated great interest in this polyphosphate (PolyP) synthesizing enzyme. PPK has wide distribution among pathogens and is involved in promoting pathogenesis, stress management and susceptibility to antibiotics. Further, the absence of a PPK orthologue in humans makes it a potential drug target. This review covers the functional and structural aspects of polyphosphate kinases in bacterial pathogens. A description of molecules being designed against PPKs has been provided, challenges associated with PPK inhibitor design are highlighted and the strategies to enable development of efficient drug against this enzyme have also been discussed.

Molecular Docking with Trehalose-6 Phosphate Phosphatase: A Potential Drug Target of Filaral Parasite ‘Brugia malayi’

2011 ◽  
Vol 8 (4) ◽  
pp. 363-370 ◽  
Author(s):  
Lakshminarayanan Karthik ◽  
Palayam Malathy ◽  
Annie Trinitta ◽  
Krishnasamy Gunasekaran
Keyword(s):  
Molecular Docking ◽  
Drug Target ◽  
Brugia Malayi ◽  
Potential Drug Target ◽  
Potential Drug

scholarly journals Activity-based protein profiling reveals deubiquitinase and aldehyde dehydrogenase targets of a cyanopyrrolidine probe

2021 ◽  
Author(s):  
Nattawadee Panyain ◽  
Aurélien Godinat ◽  
Aditya Raymond Thawani ◽  
Sofía Lachiondo-Ortega ◽  
Katie Mason ◽  
...  
Keyword(s):  
Aldehyde Dehydrogenase ◽  
Lung Fibrosis ◽  
Drug Target ◽  
Protein Profiling ◽  
Deubiquitinating Enzyme ◽  
Potential Drug Target ◽  
Potential Drug ◽  
Bona Fide ◽  
Carboxy Terminal

Ubiquitin carboxy-terminal hydrolase L1 (UCHL1), a deubiquitinating enzyme (DUB), is a potential drug target in various cancers, and liver and lung fibrosis. However, bona fide functions and substrates of UCHL1...

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