Drug development for neurodevelopmental disorders: lessons learned from fragile X syndrome
Nature Reviews Drug Discovery 17, 280 (2018).
doi:10.1038/nrd.2017.221
Authors: Elizabeth M. Berry-Kravis, Lothar Lindemann, Aia E. Jønch, George Apostol, Mark F. Bear, Randall L. Carpenter, Jacqueline N. Crawley, Aurore Curie, Vincent Des Portes, Farah Hossain, Fabrizio Gasparini, Baltazar Gomez-Mancilla, David Hessl, Eva Loth, Sebastian H. Scharf, Paul P. Wang, Florian Von Raison, Randi Hagerman, Will Spooren & Sébastien Jacquemont
Neurodevelopmental disorders such as fragile X syndrome (FXS) result in lifelong cognitive and behavioural deficits and represent a major public health burden. FXS is the...
Source: Nature Reviews Drug Discovery - December 8, 2017 Category: Drugs & Pharmacology Authors: Elizabeth M. Berry-Kravis Lothar Lindemann Aia E. J ΓΈ nch George Apostol Mark F. Bear Randall L. Carpenter Jacqueline N. Crawley Aurore Curie Vincent Des Portes Farah Hossain Fabrizio Gasparini Baltazar Gomez-Mancilla David Hessl Eva Loth Sebastian H. Sc Tags: Review Source Type: research
Drug development in the era of precision medicine
Nature Reviews Drug Discovery 17, 183 (2018).
doi:10.1038/nrd.2017.226
Authors: Sarah A. Dugger, Adam Platt & David B. Goldstein
For the past three decades, the use of genomics to inform drug discovery and development pipelines has generated both excitement and scepticism. Although earlier efforts successfully identified some new drug targets, the overall clinical efficacy of developed drugs has remained unimpressive, owing in large part (Source: Nature Reviews Drug Discovery)
Source: Nature Reviews Drug Discovery - December 8, 2017 Category: Drugs & Pharmacology Authors: Sarah A. Dugger Adam Platt David B. Goldstein Tags: Review Source Type: research
Next generation antibody drugs: pursuit of the 'high-hanging fruit'
Nature Reviews Drug Discovery 17, 197 (2018).
doi:10.1038/nrd.2017.227
Authors: Paul J. Carter & Greg A. Lazar
Antibodies are the most rapidly growing drug class and have a major impact on human health, particularly in oncology, autoimmunity and chronic inflammatory diseases. Many of the best understood and most tractable cell surface and secreted targets with known roles in human diseases have been (Source: Nature Reviews Drug Discovery)
Source: Nature Reviews Drug Discovery - December 1, 2017 Category: Drugs & Pharmacology Authors: Paul J. Carter Greg A. Lazar Tags: Review Source Type: research
Mechanistic enzymology in drug discovery: a fresh perspective
Nature Reviews Drug Discovery 17, 115 (2018).
doi:10.1038/nrd.2017.219
Authors: Geoffrey A. Holdgate, Thomas D. Meek & Rachel L. Grimley
Given the therapeutic and commercial success of small-molecule enzyme inhibitors, as exemplified by kinase inhibitors in oncology, a major focus of current drug-discovery and development efforts is on enzyme targets. Understanding the course of an enzyme-catalysed reaction can help to conceptualize different types of inhibitor (Source: Nature Reviews Drug Discovery)
Source: Nature Reviews Drug Discovery - December 1, 2017 Category: Drugs & Pharmacology Authors: Geoffrey A. Holdgate Thomas D. Meek Rachel L. Grimley Tags: Review Source Type: research
Deal watch: Roche taps potential antibiotics mine with Warp Drive Bio
Nature Reviews Drug Discovery 17, 8 (2018).
doi:10.1038/nrd.2017.247
Author: Megan Cully
Roche has entered into a strategic collaboration with Warp Drive Bio to mine bacterial genomes for novel antibiotics. The terms of the agreement, worth up to US$387 million, include an option for Roche to have a worldwide license to develop certain classes of antibiotics that (Source: Nature Reviews Drug Discovery)
Source: Nature Reviews Drug Discovery - December 1, 2017 Category: Drugs & Pharmacology Authors: Megan Cully Tags: News and Analysis Source Type: research
Cancer immunotherapy: Rewiring cancer cells
Nature Reviews Drug Discovery 16, 828 (2017).
doi:10.1038/nrd.2017.242
Author: Anna Dart
A number of factors ranging from the scarcity of tumour-specific neoantigens, tumour immunosuppression and toxicity caused by systemic delivery of immunomodulators restrict the efficiency of cancer immunotherapies. To overcome these obstacles, Nissim, Wu et al. have engineered a synthetic gene circuit enabling the production (Source: Nature Reviews Drug Discovery)
Source: Nature Reviews Drug Discovery - November 28, 2017 Category: Drugs & Pharmacology Authors: Anna Dart Tags: Research Highlight Source Type: research
GPCRs: Crystal structure of D4 dopamine receptor
Nature Reviews Drug Discovery 16, 828 (2017).
doi:10.1038/nrd.2017.236
Author: Sarah Crunkhorn
Numerous compounds are reported to interact with dopamine receptors, but the molecular mechanisms mediating dopamine receptor selectivity and activity are poorly understood. Here, Wang et al. determine crystal structures of the D4 dopamine receptor (D4R) in its inactive state bound to the (Source: Nature Reviews Drug Discovery)
Source: Nature Reviews Drug Discovery - November 28, 2017 Category: Drugs & Pharmacology Authors: Sarah Crunkhorn Tags: Research Highlight Source Type: research
Diabetes: Selective FOXO1 modulation
Nature Reviews Drug Discovery 16, 828 (2017).
doi:10.1038/nrd.2017.235
Author: Sarah Crunkhorn
Inhibition of the FOXO1 transcription factor has beneficial effects on diabetic hyperglycaemia through the suppression of glucose-6-phosphatase (G6PC) activation, but it also suppresses glucokinase (GCK) inhibition, which promotes lipogenesis. Here, Langlet et al. identify SIN3A as the corepressor required for FOXO1-mediated inhibition of GCK. (Source: Nature Reviews Drug Discovery)
Source: Nature Reviews Drug Discovery - November 28, 2017 Category: Drugs & Pharmacology Authors: Sarah Crunkhorn Tags: Research Highlight Source Type: research
Infectious disease: Fighting influenza B
Nature Reviews Drug Discovery 16, 828 (2017).
doi:10.1038/nrd.2017.234
Author: Sarah Crunkhorn
The use of broadly neutralizing antibodies against the influenza viral surface glycoprotein haemagglutinin (HA) represents a promising therapeutic approach. In mice, Shen et al. implemented several immunization regimens to induce cross-reactive antibodies against highly conserved epitopes in the HA protein of influenza B. A (Source: Nature Reviews Drug Discovery)
Source: Nature Reviews Drug Discovery - November 28, 2017 Category: Drugs & Pharmacology Authors: Sarah Crunkhorn Tags: Research Highlight Source Type: research
Polypharmacology: Repurposing ceritinib
Nature Reviews Drug Discovery 16, 828 (2017).
doi:10.1038/nrd.2017.233
Author: Sarah Crunkhorn
Network-based targeting strategies represent a promising therapeutic approach for the treatment of diseases that lack strong and actionable drivers. Using an integrated phenotypic screening and phosphoproteomics strategy, Kuenzi et al. report that the FDA-approved ALK inhibitor ceritinib exhibits activity in several ALK-negative non-small-cell lung (Source: Nature Reviews Drug Discovery)
Source: Nature Reviews Drug Discovery - November 28, 2017 Category: Drugs & Pharmacology Authors: Sarah Crunkhorn Tags: Research Highlight Source Type: research
Obesity: GDF15 tells the brain to lose weight
Nature Reviews Drug Discovery 16, 827 (2017).
doi:10.1038/nrd.2017.241
Author: M. Teresa Villanueva
Obesity treatments that do not involve invasive surgery are greatly needed. Now, a team of scientists from Amgen provide evidence that harnessing the activity of growth differentiation factor 15 (GDF15; also known as MIC1) can lower the body weight of obese mice and monkeys through (Source: Nature Reviews Drug Discovery)
Source: Nature Reviews Drug Discovery - November 28, 2017 Category: Drugs & Pharmacology Authors: M. Teresa Villanueva Tags: Research Highlight Source Type: research
BTK inhibitors get a boost
Nature Reviews Drug Discovery 16, 818 (2017).
doi:10.1038/nrd.2017.250
Author: Asher Mullard
The FDA granted accelerated approval to AstraZeneca and Acerta Pharma's acalabrutinib for mantle cell lymphoma, a second approval for the BTK inhibitor class. The agency approved AbbVie and Janssen's first-in-class BTK inhibitor, ibrutinib, in 2013 for the same indication. Ibrutinib has since picked up (Source: Nature Reviews Drug Discovery)
Source: Nature Reviews Drug Discovery - November 28, 2017 Category: Drugs & Pharmacology Authors: Asher Mullard Tags: News and Analysis Source Type: research
Second anticancer CAR T therapy receives FDA approval
Nature Reviews Drug Discovery 16, 818 (2017).
doi:10.1038/nrd.2017.249
Author: Asher Mullard
The FDA's approval of Gilead Sciences and Kite Pharmaceutical's axicabtagene ciloleucel for relapsed or refractory large B cell lymphoma in October marked the second green light for the emerging chimeric antigen receptor (CAR) T cell modality. In August, the agency approved Novartis's tisagenlecleucel (Source: Nature Reviews Drug Discovery)
Source: Nature Reviews Drug Discovery - November 28, 2017 Category: Drugs & Pharmacology Authors: Asher Mullard Tags: News and Analysis Source Type: research
FDA approves first digital pill
Nature Reviews Drug Discovery 16, 818 (2017).
doi:10.1038/nrd.2017.248
Author: Asher Mullard
The FDA approved a first drug–device product that uses a digital chip to monitor ingestion. This tracking technology could help address the costly problem of poor drug adherence in both medical practice and clinical trials, if it lives up to its promise (Nat. (Source: Nature Reviews Drug Discovery)
Source: Nature Reviews Drug Discovery - November 28, 2017 Category: Drugs & Pharmacology Authors: Asher Mullard Tags: News and Analysis Source Type: research
Cryo-electron microscopy makes waves in pharma labs
Nature Reviews Drug Discovery 16, 815 (2017).
doi:10.1038/nrd.2017.240
Author: Mark Peplow
Companies hope the Nobel Prize-winning imaging methodology will reveal biomolecule characteristics that can guide drug discovery projects. (Source: Nature Reviews Drug Discovery)
Source: Nature Reviews Drug Discovery - November 28, 2017 Category: Drugs & Pharmacology Authors: Mark Peplow Tags: News and Analysis Source Type: research
