scholarly journals Author Correction: Therapeutic manipulation of IKBKAP mis-splicing with a small molecule to cure familial dysautonomia

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Masahiko Ajiro ◽  
Tomonari Awaya ◽  
Young Jin Kim ◽  
Kei Iida ◽  
Masatsugu Denawa ◽  
...  
Keyword(s):  
Small Molecule ◽  
Familial Dysautonomia

scholarly journals Therapeutic manipulation of IKBKAP mis-splicing with a small molecule to cure familial dysautonomia

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Masahiko Ajiro ◽  
Tomonari Awaya ◽  
Young Jin Kim ◽  
Kei Iida ◽  
Masatsugu Denawa ◽  
...  
Keyword(s):  
Small Molecule ◽  
Genetic Disease ◽  
Therapeutic Strategy ◽  
Therapeutic Potential ◽  
Familial Dysautonomia ◽  
Therapeutic Modality ◽  
Aberrant Splicing ◽  
Intronic Splicing Enhancer ◽  
Exon 20 ◽  
Splicing Enhancer

AbstractApproximately half of genetic disease-associated mutations cause aberrant splicing. However, a widely applicable therapeutic strategy to splicing diseases is yet to be developed. Here, we analyze the mechanism whereby IKBKAP-familial dysautonomia (FD) exon 20 inclusion is specifically promoted by a small molecule splice modulator, RECTAS, even though IKBKAP-FD exon 20 has a suboptimal 5′ splice site due to the IVS20 + 6 T > C mutation. Knockdown experiments reveal that exon 20 inclusion is suppressed in the absence of serine/arginine-rich splicing factor 6 (SRSF6) binding to an intronic splicing enhancer in intron 20. We show that RECTAS directly interacts with CDC-like kinases (CLKs) and enhances SRSF6 phosphorylation. Consistently, exon 20 splicing is bidirectionally manipulated by targeting cellular CLK activity with RECTAS versus CLK inhibitors. The therapeutic potential of RECTAS is validated in multiple FD disease models. Our study indicates that small synthetic molecules affecting phosphorylation state of SRSFs is available as a new therapeutic modality for mechanism-oriented precision medicine of splicing diseases.

A privileged ternary blend enabling non-fullerene organic photovoltaics with over 14% efficiency

2020 ◽  
Vol 8 (43) ◽  
pp. 15135-15141
Author(s):  
Jing Yan ◽  
Yuan-Qiu-Qiang Yi ◽  
Jianqi Zhang ◽  
Huanran Feng ◽  
Yanfeng Ma ◽  
...  
Keyword(s):  
Small Molecule ◽  
Organic Photovoltaics ◽  
Power Conversion ◽  
Ternary Blend ◽  
Conversion Efficiencies

Two non-fullerene small molecule acceptors, NT-4F and NT-4Cl, were designed and synthesized. Power conversion efficiencies of 11.44% and 14.55% were achieved for NT-4Cl-based binary and ternary devices, respectively.

The small-molecule antibiotics pipeline: 2014–2018

2019 ◽  
Vol 18 (10) ◽  
pp. 739-739 ◽  
Author(s):  
Cara Lepore ◽  
Lynn Silver ◽  
Ursula Theuretzbacher ◽  
Joe Thomas ◽  
David Visi
Keyword(s):  
Small Molecule

Anisotropic forces in small molecule crystals

1985 ◽  
Vol 82 ◽  
pp. 91-97 ◽  
Author(s):  
H. Bonadeo ◽  
E. Burgos
Keyword(s):  
Small Molecule

P157 FBXO3-FBXL2 AXIS MODULATORS AS A NOVEL CLASS OF ORAL SMALL MOLECULE COMPOUNDS FOR THE TREATMENT OF CROHN’S DISEASE

2020 ◽  
Vol 158 (3) ◽  
pp. S9-S10
Author(s):  
Franca Angeli ◽  
Russell Wyborski ◽  
Bill Chen ◽  
Rama Mallampalli ◽  
Michael Lark
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Small Molecule

Targeting the p53 tumor suppressor activity in glioblastomas using small molecule MDM2-inhibitor

2011 ◽  
Vol 42 (01) ◽  
Author(s):  
P. Monfared ◽  
T. Viel ◽  
G. Schneider ◽  
Y. Waerzeggers ◽  
S. Rapic ◽  
...  
Keyword(s):  
Tumor Suppressor ◽  
Small Molecule ◽  
Suppressor Activity ◽  
P53 Tumor Suppressor ◽  
Tumor Suppressor Activity ◽  
Mdm2 Inhibitor
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