Myotonic dystrophy: candidate small molecule therapeutics

被引：43

作者：

Konieczny, Piotr ^{[1
,2
,3
]}

Selma-Soriano, Estela ^{[1
,2
,3
]}

Rapisarda, Anna S. ^{[1
,2
,3
]}

Fernandez-Costa, Juan M. ^{[1
,2
,3
]}

Perez-Alonso, Manuel ^{[1
,2
,3
]}

Artero, Ruben ^{[1
,2
,3
]}

机构：

[1] Univ Valencia, Dept Genet & Interdisciplinary Res Struct Biotech, Valencia, Spain

[2] Incliva Hlth Res Inst, Translat Genom Grp, Valencia, Spain

[3] Joint Unit Incliva CIPF, Valencia, Spain

来源：

DRUG DISCOVERY TODAY | 2017年 / 22卷 / 11期

关键词：

CUG TRINUCLEOTIDE REPEATS; DESIGNED SMALL MOLECULES; RNA TOXICITY; DROSOPHILA MODEL; MESSENGER-RNA; MBNL PROTEINS; CELL-LINES; TYPE-1; DM1; IN-VITRO; INHIBITOR;

D O I：

10.1016/j.drudis.2017.07.011

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

Myotonic dystrophy type 1 (DM1) is a rare multisystemic neuromuscular disorder caused by expansion of CTG trinucleotide repeats in the noncoding region of the DMPK gene. Mutant DMPK transcripts are toxic and alter gene expression at several levels. Chiefly, the secondary structure formed by CUGs has a strong propensity to capture and retain proteins, like those of the muscleblind-like (MBNL) family. Sequestered MBNL proteins cannot then fulfill their normal functions. Many therapeutic approaches have been explored to reverse these pathological consequences. Here, we review the myriad of small molecules that have been proposed for DM1, including examples obtained from computational rational design, HTS, drug repurposing and therapeutic gene modulation.

引用

页码：1740 / 1748

页数：9

共 67 条

[1] Development of pharmacophore models for small molecules targeting RNA: Application to the RNA repeat expansion in myotonic dystrophy type 1 [J].

Angelbello, Alicia J. ;

Gonzalez, Alex L. ;

Rzuczek, Suzanne G. ;

Disney, Matthew D. .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2016, 26 (23) :5792-5796

[2] A simple ligand that selectively targets CUG trinucleotide repeats and inhibits MBNL protein binding [J].

Arambula, Jonathan F. ;

Ramisetty, Sreenivasa Rao ;

Baranger, Anne M. ;

Zimmerman, Steven C. .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2009, 106 (38) :16068-16073

[3] Immortalized human myotonic dystrophy muscle cell lines to assess therapeutic compounds [J].

Arandel, Ludovic ;

Espinoza, Micaela Polay ;

Matloka, Magdalena ;

Bazinet, Audrey ;

Diniz, Damily De Dea ;

Naouar, Naira ;

Rau, Frederique ;

Jollet, Arnaud ;

Edom-Vovard, Frederique ;

Mamchaoui, Kamel ;

Tarnopolsky, Mark ;

Puymirat, Jack ;

Battail, Christophe ;

Boland, Anne ;

Deleuze, Jean-Francois ;

Mouly, Vincent ;

Klein, Arnaud F. ;

Furling, Denis .

DISEASE MODELS & MECHANISMS, 2017, 10 (04) :487-497

[4] Increased autophagy and apoptosis contribute to muscle atrophy in a myotonic dystrophy type 1 Drosophila model [J].

Bargiela, Ariadna ;

Cerro-Herreros, Estefania ;

Fernandez-Costa, Juan M. ;

Vilchez, Juan J. ;

Llamusi, Beatriz ;

Artero, Ruben .

DISEASE MODELS & MECHANISMS, 2015, 8 (07) :679-690

[5] Loss of MBNL Leads to Disruption of Developmentally Regulated Alternative Polyadenylation in RNA-Mediated Disease [J].

Batra, Ranjan ;

Charizanis, Konstantinos ;

Manchanda, Mini ;

Mohan, Apoorva ;

Li, Moyi ;

Finn, Dustin J. ;

Goodwin, Marianne ;

Zhang, Chaolin ;

Sobczak, Krzysztof ;

Thornton, Charles A. ;

Swanson, Maurice S. .

MOLECULAR CELL, 2014, 56 (02) :311-322

[6] Targeting deregulated AMPK/mTORC1 pathways improves muscle function in myotonic dystrophy type I [J].

Brockhoff, Marielle ;

Rion, Nathalie ;

Chojnowska, Kathrin ;

Wiktorowicz, Tatiana ;

Eickhorst, Christopher ;

Erne, Beat ;

Frank, Stephan ;

Angelini, Corrado ;

Furling, Denis ;

Rueegg, Markus A. ;

Sinnreich, Michael ;

Castets, Perrine .

JOURNAL OF CLINICAL INVESTIGATION, 2017, 127 (02) :549-563

[7] Pentamidine rescues contractility and rhythmicity in a Drosophila model of myotonic dystrophy heart dysfunction [J].

Chakraborty, Mouli ;

Selma-Soriano, Estela ;

Magny, Emile ;

Couso, Juan Pablo ;

Perez-Alonso, Manuel ;

Charlet-Berguerand, Nicolas ;

Artero, Ruben ;

Llamusi, Beatriz .

DISEASE MODELS & MECHANISMS, 2015, 8 (12) :1569-1578

[8] Two high-throughput screening assays for aberrant RNA-protein interactions in myotonic dystrophy type 1 [J].

Chen, Catherine Z. ;

Sobczak, Krzysztof ;

Hoskins, Jason ;

Southall, Noel ;

Marugan, Juan J. ;

Zheng, Wei ;

Thornton, Charles A. ;

Austin, Christopher P. .

ANALYTICAL AND BIOANALYTICAL CHEMISTRY, 2012, 402 (05) :1889-1898

[9] Disorganization of white matter architecture in major depressive disorder: a meta-analysis of diffusion tensor imaging with tract-based spatial statistics [J].

Chen, Guangxiang ;

Hu, Xinyu ;

Li, Lei ;

Huang, Xiaoqi ;

Lui, Su ;

Kuang, Weihong ;

Ai, Hua ;

Bi, Feng ;

Gu, Zhongwei ;

Gong, Qiyong .

SCIENTIFIC REPORTS, 2016, 6

[10] Induction and reversal of myotonic dystrophy type 1 pre-mRNA splicing defects by small molecules [J].

Childs-Disney, Jessica L. ;

Stepniak-Konieczna, Ewa ;

Tuan Tran ;

Yildirim, Ilyas ;

Park, HaJeung ;

Chen, Catherine Z. ;

Hoskins, Jason ;

Southall, Noel ;

Marugan, Juan J. ;

Patnaik, Samarjit ;

Zheng, Wei ;

Austin, Chris P. ;

Schatz, George C. ;

Sobczak, Krzysztof ;

Thornton, Charles A. ;

Disney, Matthew D. .

NATURE COMMUNICATIONS, 2013, 4

← 1 2 3 4 5 6 7 →