Journal ArticleDOI
State-of-the-art strategies for targeting protein–protein interactions by small-molecule inhibitors
TLDR
The successful cases from the recent five year studies are used to illustrate how these approaches are implemented to uncover and optimize small molecule PPI inhibitors and notably some of them have become promising therapeutics.Abstract:
Correction for 'State-of-the-art strategies for targeting protein-protein interactions by small-molecule inhibitors' by Chunquan Sheng et al., Chem. Soc. Rev., 2015, DOI: 10.1039/c5cs00252d.read more
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Recent advances in the development of protein-protein interactions modulators: mechanisms and clinical trials.
TL;DR: This work summarizes the recent advances in PPIs modulators, including small molecules, peptides, and antibodies, hoping to provide some guidance to the design of novel drugs targeting PPIs in the future.
Journal ArticleDOI
Orally Absorbed Cyclic Peptides
Daniel S. Nielsen,Nicholas E. Shepherd,Weijun Xu,Andrew J. Lucke,Martin J. Stoermer,David P. Fairlie +5 more
TL;DR: The cyclic peptides violated to different degrees all of the limits traditionally considered to be important for oral bioavailability of drug-like small molecules, although fewer hydrogen bond donors and reduced flexibility generally favored oral absorption.
Journal ArticleDOI
Drugging Ras GTPase: a comprehensive mechanistic and signaling structural view
TL;DR: To mitigate drug resistance, this review proposes signaling pathways that can be co-targeted along with Ras and explains why, and postulates that these and Ras signaling pathways act independently and in corresponding ways in cell cycle control.
Journal ArticleDOI
Allosteric Activation Dictates PRC2 Activity Independent of Its Recruitment to Chromatin
Chul Hwan Lee,Chul Hwan Lee,Jia Ray Yu,Jia Ray Yu,Sunil Kumar,Ying Jin,Gary LeRoy,Gary LeRoy,Natarajan V. Bhanu,Syuzo Kaneko,Syuzo Kaneko,Benjamin A. Garcia,Andrew D. Hamilton,Danny Reinberg,Danny Reinberg +14 more
TL;DR: With genetic and chemical tools, it is demonstrated that targeting allosteric activation overrode the gain-of-function effect of EZH2Y646X oncogenic mutations and revealed critical implications for the regulation and biology of PRC2 and a vulnerability in tacklingPRC2-addicted cancers.
Journal ArticleDOI
Small Molecule Inhibition of Ligand-Stimulated RAGE-DIAPH1 Signal Transduction.
Michaele B. Manigrasso,Jinhong Pan,Vivek Rai,Jinghua Zhang,Sergey Reverdatto,Nosirudeen Quadri,Robert J. DeVita,Ravichandran Ramasamy,Alexander Shekhtman,Ann Marie Schmidt +9 more
TL;DR: NMR spectroscopy and x-ray crystallization studies of the extracellular domains of RAGE indicate that RAGE ligands bind by distinct charge- and hydrophobicity-dependent mechanisms, and provide support for the feasibility of inhibition of protein-protein interaction (PPI).
References
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In vivo activation of the p53 pathway by small-molecule antagonists of MDM2.
Lyubomir T. Vassilev,Binh Thanh Vu,Bradford Graves,Daisy Carvajal,Frank John Podlaski,Zoran Filipovic,Norman Kong,Ursula Kammlott,Christine Lukacs,Christian Klein,Nader Fotouhi,Liu Emily Aijun +11 more
TL;DR: In this article, the authors identify potent and selective small-molecule antagonists of MDM2 and confirm their mode of action through the crystal structures of complexes, leading to cell cycle arrest, apoptosis, and growth inhibition of human tumor xenografts.
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An inhibitor of Bcl-2 family proteins induces regression of solid tumours
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Keap1 represses nuclear activation of antioxidant responsive elements by Nrf2 through binding to the amino-terminal Neh2 domain
Ken Itoh,Nobunao Wakabayashi,Yasutake Katoh,Tetsuro Ishii,Kazuhiko Igarashi,James Douglas Engel,James Douglas Engel,Masayuki Yamamoto +7 more
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