Small molecules against RNA targets attract big backers
Nature Reviews Drug Discovery 16, 813 (2017).
doi:10.1038/nrd.2017.239
Author: Asher Mullard
Novartis, Merck, Pfizer and biotech entrepreneurs have started working on small-molecule drugs that act on an assortment of RNA targets, hoping to unlock once undruggable targets and new biology. (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
Steps forward for cancer precision medicine
Nature Reviews Drug Discovery 17, 1 (2018).
doi:10.1038/nrd.2017.218
Authors: Roberto Salgado, Helen Moore, John W. M. Martens, Tracy Lively, Shakun Malik, Ultan McDermott, Stefan Michiels, Jeffrey A. Moscow, Sabine Tejpar, Tawnya McKee & Denis Lacombe
The availability of targeted anticancer drugs and the relative affordability of genomic analyses has led to a growing expectation among patients with cancer that they can receive personalized treatment based on the genomic signature of their tumour. Here, we discuss some of the challenges and (Source: Nature Reviews Drug Discovery)
Source: Nature Reviews Drug Discovery - November 24, 2017 Category: Drugs & Pharmacology Authors: Roberto Salgado Helen Moore John W. M. Martens Tracy Lively Shakun Malik Ultan McDermott Stefan Michiels Jeffrey A. Moscow Sabine Tejpar Tawnya McKee Denis Lacombe Tags: Comment Source Type: research
Emptying the stores: lysosomal diseases and therapeutic strategies
Nature Reviews Drug Discovery 17, 133 (2018).
doi:10.1038/nrd.2017.214
Author: Frances M. Platt
Lysosomal storage disorders (LSDs) — designated as 'orphan' diseases — are inborn errors of metabolism caused by defects in genes that encode proteins involved in various aspects of lysosomal homeostasis. For many years, LSDs were viewed as unattractive targets for the development of therapies owing (Source: Nature Reviews Drug Discovery)
Source: Nature Reviews Drug Discovery - November 17, 2017 Category: Drugs & Pharmacology Authors: Frances M. Platt Tags: Review Source Type: research
Cancer: Bispecific antibody directs T cells to solid tumours
Nature Reviews Drug Discovery 16, 826 (2017).
doi:10.1038/nrd.2017.237
Author: Megan Cully
Using T cells to attack solid tumours is an attractive option for the treatment of cancer, but requires the presence of a neoantigen on the tumour to engage the T cell. A new paper from Chugai Pharmaceutical uses a bispecific antibody, ERY974, to direct T (Source: Nature Reviews Drug Discovery)
Source: Nature Reviews Drug Discovery - November 17, 2017 Category: Drugs & Pharmacology Authors: Megan Cully Tags: Research Highlight Source Type: research
Metabolic disease: Ectopic olfactory receptor activation reverses obesity
Nature Reviews Drug Discovery 16, 826 (2017).
doi:10.1038/nrd.2017.230
Author: Sarah Crunkhorn
Accumulating evidence indicates that olfactory receptors (ORs) are not only expressed in the olfactory epithelium, but may be found throughout the body and function in a broad range of cellular processes. Now, writing in The Journal of Clinical Investigation, Lee and colleagues report a (Source: Nature Reviews Drug Discovery)
Source: Nature Reviews Drug Discovery - November 17, 2017 Category: Drugs & Pharmacology Authors: Sarah Crunkhorn Tags: Research Highlight Source Type: research
Sepsis: Stalking a new target
Nature Reviews Drug Discovery 16, 825 (2017).
doi:10.1038/nrd.2017.238
Author: Katie Kingwell
Sepsis is a potentially lethal systemic condition that arises from a dysregulated host immune response to infection and for which effective, targeted therapies are lacking. A recent study by Tang and colleagues has identified anaplastic lymphoma kinase (ALK) as an important driver of immune responses (Source: Nature Reviews Drug Discovery)
Source: Nature Reviews Drug Discovery - November 17, 2017 Category: Drugs & Pharmacology Authors: Katie Kingwell Tags: Research Highlight Source Type: research
Eric Rubin
Nature Reviews Drug Discovery 16, 820 (2017).
doi:10.1038/nrd.2017.228
Eric Rubin started as Vice President of clinical oncology at Merck & Co. in 2008. Since then, he has helped to turn the PD1-targeting pembrolizumab from an almost forgotten antibody into a blockbuster immunotherapy. He also secured a first approval for a tumour-agnostic cancer indication with pembrolizumab earlier this year, and is overseeing more than 300 combination trials to push this drug into more oncology settings. He spoke with Asher Mullard about the future of tumour-agnostic cancer approvals, the complexity of immunotherapy combinat...
Source: Nature Reviews Drug Discovery - November 17, 2017 Category: Drugs & Pharmacology Tags: News and Analysis Source Type: research
The atopic dermatitis market
Nature Reviews Drug Discovery 17, 237 (2018).
doi:10.1038/nrd.2017.192
Authors: Eleni Pantazi, Gianluca Valenza, Manuela Hess & Bashar Hamad
The market for atopic dermatitis therapies is dominated by topical corticosteroids, but is poised to change with the recent approvals of dupilumab and crisaborole, as well as other drugs in clinical development. (Source: Nature Reviews Drug Discovery)
Source: Nature Reviews Drug Discovery - November 6, 2017 Category: Drugs & Pharmacology Authors: Eleni Pantazi Gianluca Valenza Manuela Hess Bashar Hamad Tags: News and Analysis Source Type: research
JAK inhibition as a therapeutic strategy for immune and inflammatory diseases
Nature Reviews Drug Discovery 16, 843 (2017).
doi:10.1038/nrd.2017.201
Authors: Daniella M. Schwartz, Yuka Kanno, Alejandro Villarino, Michael Ward, Massimo Gadina & John J. O'Shea
The discovery of cytokines as key drivers of immune-mediated diseases has spurred efforts to target their associated signalling pathways. Janus kinases (JAKs) are essential signalling mediators downstream of many pro-inflammatory cytokines, and small-molecule inhibitors of JAKs (jakinibs) have gained traction as safe and efficacious options (Source: Nature Reviews Drug Discovery)
Source: Nature Reviews Drug Discovery - November 6, 2017 Category: Drugs & Pharmacology Authors: Daniella M. Schwartz Yuka Kanno Alejandro Villarino Michael Ward Massimo Gadina John J. O'Shea Tags: Review Source Type: research
Emerging therapies for idiopathic pulmonary fibrosis, a progressive age-related disease
Nature Reviews Drug Discovery 16, 810 (2017).
doi:10.1038/nrd.2017.225
Author: Ana L. Mora, Mauricio Rojas, Annie Pardo & Moises Selman
Nature Reviews Drug Discovery16, 755–772 (2017)In the original version, navitoclax was incorrectly referred to as an apoptosis inhibitor in Figure 3. The error has been corrected online. (Source: Nature Reviews Drug Discovery)
Source: Nature Reviews Drug Discovery - October 30, 2017 Category: Drugs & Pharmacology Authors: Ana L. Mora Mauricio Rojas Annie Pardo Moises Selman Tags: Corrigendum Source Type: research
Cancer: Reducing melanoma in redheads
Nature Reviews Drug Discovery 16, 754 (2017).
doi:10.1038/nrd.2017.209
Author: Sarah Crunkhorn
The G protein-coupled melanocortin-1 receptor (MC1R) mediates melanin production, which protects the skin from UV radiation. However, almost all red-haired individuals have a variant of MC1R with reduced or absent signalling capacity and are therefore at higher risk of developing melanomas. Chen et al. (Source: Nature Reviews Drug Discovery)
Source: Nature Reviews Drug Discovery - October 30, 2017 Category: Drugs & Pharmacology Authors: Sarah Crunkhorn Tags: Research Highlight Source Type: research
HIV: Trispecific antibodies block infection
Nature Reviews Drug Discovery 16, 754 (2017).
doi:10.1038/nrd.2017.208
Author: Sarah Crunkhorn
The use of broadly neutralizing antibodies (bnAbs) isolated from HIV-infected individuals in the development of an effective AIDS vaccine has been limited by potency and breadth of protection. Now, Xu et al. report the generation of multi-specific antibodies derived from bnAbs with specificities for (Source: Nature Reviews Drug Discovery)
Source: Nature Reviews Drug Discovery - October 30, 2017 Category: Drugs & Pharmacology Authors: Sarah Crunkhorn Tags: Research Highlight Source Type: research
Transplantation: Combining OX40L and mTOR blockade
Nature Reviews Drug Discovery 16, 754 (2017).
doi:10.1038/nrd.2017.207
Author: Sarah Crunkhorn
Controlling alloimmunity after transplantation remains a significant challenge, as existing immunosuppressive agents typically inhibit both effector T (Teff) and regulatory T (Treg) cells. Using the non-human primate graft-versus-host disease (GVHD) model, Tkachev et al. now demonstrate that the combination of (Source: Nature Reviews Drug Discovery)
Source: Nature Reviews Drug Discovery - October 30, 2017 Category: Drugs & Pharmacology Authors: Sarah Crunkhorn Tags: Research Highlight Source Type: research
Cancer immunotherapy: Targeting regulatory T cells
Nature Reviews Drug Discovery 16, 754 (2017).
doi:10.1038/nrd.2017.206
Author: Sarah Crunkhorn
The immunosuppressive actions of regulatory T (Treg) cells have limited the success of cancer immunotherapies. Grinberg-Bleyer et al. show that ablation of the canonical nuclear factor κB (NF-κB) subunit c-rel specifically impairs the generation and maintenance of activated Treg cells (Source: Nature Reviews Drug Discovery)
Source: Nature Reviews Drug Discovery - October 30, 2017 Category: Drugs & Pharmacology Authors: Sarah Crunkhorn Tags: Research Highlight Source Type: research
G protein-coupled receptors: Gut feeling on bacterial GPCR agonists
Nature Reviews Drug Discovery 16, 754 (2017).
doi:10.1038/nrd.2017.205
Author: Megan Cully
The mechanisms through which microorganisms in the gut affect human health are poorly defined. Writing in Nature, Cohen and colleagues describe commensal bacterial metabolites that activate G protein-coupled receptors (GPCRs) in the intestine, including GPR119, thereby improving glucose tolerance in mice.In previous work, (Source: Nature Reviews Drug Discovery)
Source: Nature Reviews Drug Discovery - October 30, 2017 Category: Drugs & Pharmacology Authors: Megan Cully Tags: Research Highlight Source Type: research
