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Nature Reviews. Drug Discovery

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https://www.readbyqxmd.com/read/27910877/a-comprehensive-map-of-molecular-drug-targets
#1
Rita Santos, Oleg Ursu, Anna Gaulton, A Patrícia Bento, Ramesh S Donadi, Cristian G Bologa, Anneli Karlsson, Bissan Al-Lazikani, Anne Hersey, Tudor I Oprea, John P Overington
The success of mechanism-based drug discovery depends on the definition of the drug target. This definition becomes even more important as we try to link drug response to genetic variation, understand stratified clinical efficacy and safety, rationalize the differences between drugs in the same therapeutic class and predict drug utility in patient subgroups. However, drug targets are often poorly defined in the literature, both for launched drugs and for potential therapeutic agents in discovery and development...
December 2, 2016: Nature Reviews. Drug Discovery
https://www.readbyqxmd.com/read/27910876/drug-launch-curves-in-the-modern-era
#2
Seth Robey, Frank S David
No abstract text is available yet for this article.
December 2, 2016: Nature Reviews. Drug Discovery
https://www.readbyqxmd.com/read/27885283/induced-protein-degradation-an-emerging-drug-discovery-paradigm
#3
Ashton C Lai, Craig M Crews
Small-molecule drug discovery has traditionally focused on occupancy of a binding site that directly affects protein function, and this approach typically precludes targeting proteins that lack such amenable sites. Furthermore, high systemic drug exposures may be needed to maintain sufficient target inhibition in vivo, increasing the risk of undesirable off-target effects. Induced protein degradation is an alternative approach that is event-driven: upon drug binding, the target protein is tagged for elimination...
November 25, 2016: Nature Reviews. Drug Discovery
https://www.readbyqxmd.com/read/27885282/genome-wide-association-studies-of-drug-response-and-toxicity-an-opportunity-for-genome-medicine
#4
Kathleen M Giacomini, Sook Wah Yee, Taisei Mushiroda, Richard M Weinshilboum, Mark J Ratain, Michiaki Kubo
No abstract text is available yet for this article.
November 25, 2016: Nature Reviews. Drug Discovery
https://www.readbyqxmd.com/read/27857143/cancer-blocking-metastasis
#5
Sarah Crunkhorn
No abstract text is available yet for this article.
November 18, 2016: Nature Reviews. Drug Discovery
https://www.readbyqxmd.com/read/27857142/antibacterial-agents-microbiome-derived-antibiotic-identified
#6
Sarah Crunkhorn
No abstract text is available yet for this article.
November 18, 2016: Nature Reviews. Drug Discovery
https://www.readbyqxmd.com/read/27857141/hiv-achieving-sustained-remission
#7
Sarah Crunkhorn
No abstract text is available yet for this article.
November 18, 2016: Nature Reviews. Drug Discovery
https://www.readbyqxmd.com/read/27857140/immune-disorders-blocking-the-alternative-complement-pathway
#8
Sarah Crunkhorn
No abstract text is available yet for this article.
November 18, 2016: Nature Reviews. Drug Discovery
https://www.readbyqxmd.com/read/27857139/drug-design-cannabinoid-receptor-structure-revealed
#9
Sarah Crunkhorn
No abstract text is available yet for this article.
November 18, 2016: Nature Reviews. Drug Discovery
https://www.readbyqxmd.com/read/27857138/market-watch-antibacterial-innovation-in-european-smes
#10
Ursula Theuretzbacher
No abstract text is available yet for this article.
November 18, 2016: Nature Reviews. Drug Discovery
https://www.readbyqxmd.com/read/27857137/metabolic-disorders-hormone-conjugate-combats-metabolic-syndrome
#11
Sarah Crunkhorn
No abstract text is available yet for this article.
November 18, 2016: Nature Reviews. Drug Discovery
https://www.readbyqxmd.com/read/27833121/calpain-research-for-drug-discovery-challenges-and-potential
#12
Yasuko Ono, Takaomi C Saido, Hiroyuki Sorimachi
Calpains are a family of proteases that were scientifically recognized earlier than proteasomes and caspases, but remain enigmatic. However, they are known to participate in a multitude of physiological and pathological processes, performing 'limited proteolysis' whereby they do not destroy but rather modulate the functions of their substrates. Calpains are therefore referred to as 'modulator proteases'. Multidisciplinary research on calpains has begun to elucidate their involvement in pathophysiological mechanisms...
November 11, 2016: Nature Reviews. Drug Discovery
https://www.readbyqxmd.com/read/27811931/phase-ii-and-phase-iii-failures-2013-2015
#13
Richard K Harrison
No abstract text is available yet for this article.
November 4, 2016: Nature Reviews. Drug Discovery
https://www.readbyqxmd.com/read/27811930/defining-the-brain-circuits-involved-in-psychiatric-disorders-imi-newmeds
#14
Francesc Artigas, Esther Schenker, Pau Celada, Michael Spedding, Laia Lladó-Pelfort, Noemi Jurado, Mercedes Núñez, Noemi Santana, Eva Troyano-Rodriguez, Maurizio S Riga, Hanna van den Munkhof, Anna Castañé, Hamdy Shaban, Thérèse M Jay, Anushree Tripathi, Bill P Godsil, Claude Sebban, Jean Mariani, Philippe Faure, Samir Takkilah, Zoe A Hughes, Chester J Siok, Mihaily Hajos, Karsten Wicke, Natalia Gass, Wolfgang Weber-Fahr, Alexander Sartorius, Robert Becker, Michael Didriksen, Jesper F Bastlund, Mark Tricklebank, Céline Risterucci, Andreas Meyer-Lindenberg, Adam J Schwarz
Despite the vast amount of research on schizophrenia and depression in the past two decades, there have been few innovative drugs to treat these disorders. Precompetitive research collaborations between companies and academic groups can help tackle this innovation deficit, as illustrated by the achievements of the IMI-NEWMEDS consortium.
November 4, 2016: Nature Reviews. Drug Discovery
https://www.readbyqxmd.com/read/27811929/tumour-associated-mesenchymal-stem-stromal-cells-emerging-therapeutic-targets
#15
Yufang Shi, Liming Du, Liangyu Lin, Ying Wang
Mesenchymal stem cells, also known as mesenchymal stromal cells (MSCs), exist in many tissues and are known to actively migrate to sites of tissue injury, where they participate in wound repair. Tumours can be considered "wounds that never heal" and, in response to cues from a tumour, MSCs are continuously recruited to and become integral components of the tumour microenvironment. Recently, it has become apparent that such tumour-associated MSCs (TA-MSCs) have an active role in tumour initiation, promotion, progression and metastasis...
November 4, 2016: Nature Reviews. Drug Discovery
https://www.readbyqxmd.com/read/27807347/aptamers-as-targeted-therapeutics-current-potential-and-challenges
#16
Jiehua Zhou, John Rossi
Nucleic acid aptamers, often termed 'chemical antibodies', are functionally comparable to traditional antibodies, but offer several advantages, including their relatively small physical size, flexible structure, quick chemical production, versatile chemical modification, high stability and lack of immunogenicity. In addition, many aptamers are internalized upon binding to cellular receptors, making them useful targeted delivery agents for small interfering RNAs (siRNAs), microRNAs and conventional drugs. However, several crucial factors have delayed the clinical translation of therapeutic aptamers, such as their inherent physicochemical characteristics and lack of safety data...
November 3, 2016: Nature Reviews. Drug Discovery
https://www.readbyqxmd.com/read/27765941/regulatory-watch-innovative-drug-availability-in-china
#17
Liming Shao, Lili Xu, Qiu Li, Ranjana Chakravarthy, Ziling Yang, Kenneth I Kaitin
No abstract text is available yet for this article.
October 21, 2016: Nature Reviews. Drug Discovery
https://www.readbyqxmd.com/read/27765940/epigenetic-drug-discovery-breaking-through-the-immune-barrier
#18
David F Tough, Paul P Tak, Alexander Tarakhovsky, Rab K Prinjha
Immune-mediated diseases are clinically heterogeneous but they share genetic and pathogenic mechanisms. These diseases may develop from the interplay of genetic factors and environmental or lifestyle factors. Exposure to such factors, including infectious agents, is associated with coordinated changes in gene transcription owing to epigenetic alterations. A growing understanding of how epigenetic mechanisms control gene expression patterns and cell function has been aided by the development of small-molecule inhibitors that target these processes...
October 21, 2016: Nature Reviews. Drug Discovery
https://www.readbyqxmd.com/read/27739512/precision-medicine-and-the-changing-role-of-regulatory-agencies
#19
Alasdair Breckenridge, Hans-Georg Eichler, Jonathan P Jarow
The growth of precision medicine presents challenges for the regulators of medicines, related to aspects that include the basis of evidence generation, patient involvement in the regulatory process, cost of new medicines and the need for new regulatory models. It also raises questions about the tolerance of risk, especially with early interventions for life-threatening diseases.
October 14, 2016: Nature Reviews. Drug Discovery
https://www.readbyqxmd.com/read/27725635/envelope-specific-antibodies-and-antibody-derived-molecules-for-treating-and-curing-hiv-infection
#20
Guido Ferrari, Barton F Haynes, Scott Koenig, Jeffrey L Nordstrom, David M Margolis, Georgia D Tomaras
HIV-1 is a retrovirus that integrates into host chromatin and can remain transcriptionally quiescent in a pool of immune cells. This characteristic enables HIV-1 to evade both host immune responses and antiretroviral drugs, leading to persistent infection. Upon reactivation of proviral gene expression, HIV-1 envelope (HIV-1 Env) glycoproteins are expressed on the cell surface, transforming latently infected cells into targets for HIV-1 Env-specific monoclonal antibodies (mAbs), which can engage immune effector cells to kill productively infected CD4(+) T cells and thus limit the spread of progeny virus...
October 7, 2016: Nature Reviews. Drug Discovery
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