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Drug Discovery Today

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https://www.readbyqxmd.com/read/30414950/strategies-for-brain-targeting-liposomal-delivery-of-small-hydrophobic-molecules-in-the-treatment-of-neurodegenerative-diseases
#1
REVIEW
Zi-Ying Wang, Sravan Gopalkrishnashetty Sreenivasmurthy, Ju-Xian Song, Jingyi Liu, Min Li
Neurodegenerative diseases (NDs), including Alzheimer's disease (AD) and Parkinson's disease (PD), threaten the health of an ever-growing number of older people worldwide; so far, there are no effective cures. Significant efforts have been devoted to developing new drugs for NDs in recent years, and some small molecules have been shown to be promising in preclinical studies. However, the major challenge for brain-targeting drugs is how to efficiently deliver the drugs across the blood-brain barrier (BBB) to desired targets...
November 8, 2018: Drug Discovery Today
https://www.readbyqxmd.com/read/30408529/therapeutic-potential-of-endogenous-stem-cells-and-cellular-factors-for-scar-free-skin-regeneration
#2
REVIEW
Shibashish Giri, Hans-Günther Machens, Augustinus Bader
Injured human skin fails to regenerate, resulting in scar formation. Annually, 100 million new skin-scarring incidents, occurring as a result of surgery, disease, burns, or sports-related damage, remain untreated. Here, we review knowledge gained from scar-free experimental animal models that have natural regenerative mechanisms for scar-free skin recovery. We also focus on the unique role of endogenous stem cells and other cellular and molecular factors, including the balance of the transforming growth factor-beta (TGF-β) pathway in the context of human skin regeneration...
November 5, 2018: Drug Discovery Today
https://www.readbyqxmd.com/read/30408528/interplay-between-hereditary-and-environmental-factors-to-establish-an-in-vitro-disease-model-of-keratoconus
#3
REVIEW
Subhadeep Roy, Saumya Yadav, Tanushree Dasgupta, Shikha Chawla, Radhika Tandon, Sourabh Ghosh
Keratoconus (KC) is a bilateral corneal dystrophy and a multifactorial, multigenic disorder with an etiology involving a strong environmental component and complex inheritance patterns. The underlying pathophysiology of KC is poorly understood because of potential crosstalk between genetic-epigenetic variants possibly triggered by the environmental factors. Here, we decode the etiopathological basis of KC using genomic, transcriptomic, proteomic and metabolic approaches. The lack of relevant models that accurately imitate this condition has been particularly limiting in terms of the effective management of KC...
November 5, 2018: Drug Discovery Today
https://www.readbyqxmd.com/read/30408527/growing-synergy-of-nanodiamonds-in-neurodegenerative-interventions
#4
REVIEW
Jackson Saraf, Kiran Kalia, Pallab Bhattacharya, Rakesh Kumar Tekade
Neurodegenerative diseases are complex in both their nature and prognosis. The difficulties associated with penetrating the blood-brain barrier (BBB), achieving site-specific targeting to the brain, and identifying the genetic etiologies responsible make treating neurodegenerative diseases, such as Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), amyotrophic lateral sclerosis (ALS), and stroke, challenging. The aim to treat disease at the molecular level has galvanized nanotechnology research...
November 5, 2018: Drug Discovery Today
https://www.readbyqxmd.com/read/30399443/evolution-of-commercially-available-compounds-for-hts
#5
REVIEW
Dmitriy M Volochnyuk, Sergey V Ryabukhin, Yurii Moroz, Olena Savych, Alexander Chuprina, Dragos Horvath, Yuliana Zabolotna, Alexandre Varnek, Duncan B Judd
Over recent years, an industry of compound suppliers has grown to provide drug discovery with screening compounds: it is estimated that there are over 16 million compounds available from these sources. Here, we review the chemical space covered by suppliers' compound libraries (SCL) in terms of compound chemophysical properties, novelty, diversity, and quality. We examine the feasibility of compiling high-quality vendor-based libraries avoiding complicated, expensive compound management activity, and compare the resulting libraries to the ChEMBL data set...
November 3, 2018: Drug Discovery Today
https://www.readbyqxmd.com/read/30395928/microtransplantation-of-human-brain-receptors-into-oocytes-to-tackle-key-questions-in-drug-discovery
#6
REVIEW
Ruud Zwart, Francesca Mazzo, Emanuele Sher
It is important in drug discovery to demonstrate that activity of novel drugs found by screening on recombinant receptors translates to activity on native human receptors in brain areas affected by disease. In this review, we summarise the development and use of the microtransplantation technique. Native receptors are reconstituted from human brain tissues into oocytes from the frog Xenopus laevis where they can be functionally assessed. Oocytes microtransplanted with hippocampal tissue from an epileptic patient were used to demonstrate that new antiepileptic agents act on receptors in diseased tissue...
November 3, 2018: Drug Discovery Today
https://www.readbyqxmd.com/read/30391204/micro-and-nano-formulations-for-bioprinting-and-additive-manufacturing
#7
REVIEW
Guillaume Bouguéon, Tina Kauss, Bérangère Dessane, Philippe Barthélémy, Sylvie Crauste-Manciet
Recent developments in bioprinting have enabled an optimized formulation of bioinks by incorporating pharmaceuticals into cell-containing gel matrices. The proof-of-printability of a variety of forms has been provided, such as particles and fibers in the nanometric or micrometric range like dendrimers or micelles, although this is still lacking for some (liposomes for example). Resulting composite bioinks have the advantage of (i) improving cell growth and differentiation, (ii) delivering active molecules or (iii) improving mechanical properties of bioinks, printed scaffolds or the printing process...
November 1, 2018: Drug Discovery Today
https://www.readbyqxmd.com/read/30367995/foxo1-mirna-interacting-networks-as-potential-targets-for-mitochondrial-diseases
#8
REVIEW
Prasanth Puthanveetil
Mitochondrial homeostasis is important for the health and well-being of organ systems and organisms. Mitochondrial dysfunction is known to be the cause and consequence of metabolic diseases, including obesity, diabetes, cancer, neurodegeneration, cerebrovascular, and cardiovascular disease. For cardiovascular tissue, which relies mostly on oxidative phosphorylation, the role of mitochondria is inevitable. Rather than being biomarkers of mitochondrial health, miRNAs are now known as bioregulators of this important feature...
October 24, 2018: Drug Discovery Today
https://www.readbyqxmd.com/read/30366058/using-molecular-mimicry-inducing-pathways-of-pathogens-as-novel-drug-targets
#9
REVIEW
Anjali Garg, Bandana Kumari, Neelja Singhal, Manish Kumar
Several microbial pathogens cause autoimmune diseases in humans by exhibiting molecular mimicry with the host proteins. However, the contribution of autoimmunity in microbial pathogenesis has not been evaluated critically. Clinical and experimental observations have supported and corroborated that autoimmunity was a fundamental process underlying pathology of human tuberculosis bacteria. In the current review, we propose novel drug targets based on a pathogen's molecular-mimicry-inducing proteins. The process for identification of drug targets has been explained using Mycobacterium tuberculosis as a model organism...
October 23, 2018: Drug Discovery Today
https://www.readbyqxmd.com/read/30359770/the-power-of-combining-phenotypic-and-target-focused-drug-discovery
#10
REVIEW
Ralf Heilker, Uta Lessel, Daniel Bischoff
A fierce dispute has arisen between the supporters of phenotypic and target-focused screening regarding which path grants the higher probability of successful drug development. A chance to reconcile these two approaches lies in successful target deconvolution (TD) after phenotypic screens. But, despite the panoply of available in vitro TD methods, the task of matching a phenotypically active compound with a biomolecular target remains challenging. Consequently, this review details the latest developments of in silico techniques that expedite TD...
October 22, 2018: Drug Discovery Today
https://www.readbyqxmd.com/read/30342247/can-lifecycle-management-safeguard-innovation-in-the-pharmaceutical-industry
#11
REVIEW
Stefanie Hering, Brigitta Loretz, Thomas Friedli, Claus-Michael Lehr, Frank Stieneker
The pharmaceutical industry invests enormous amounts of resources (>€1 billion and >10years) in the development of new products. External factors such as intensifying foreign competition and greater regulatory demands can negatively affect the profit margin, whereas the R&D productivity diminishes. To stay competitive and to maintain high R&D capabilities for developing new medicinal products, companies must make smart investment decisions to maximize their return on investment. Consequently, the entire lifecycle of a medicinal product must be effectively managed to ensure a sustained development through commercialization...
October 17, 2018: Drug Discovery Today
https://www.readbyqxmd.com/read/30342246/artificial-intelligence-and-its-potential-in-oncology
#12
REVIEW
Vaishali Y Londhe, Bhavya Bhasin
The two main branches associated with Artificial Intelligence (AI) in medicine are virtual and physical. The virtual component includes machine learning (ML) and algorithms, whereas physical AI includes medical devices and robots for delivering care. AI is used successfully in tumour segmentation, histopathological diagnosis, tracking tumour development, and prognosis prediction. CURATE.AI, developed at the National University of Singapore, is a platform that automatically decides the optimum dose of drugs for a durable response, allowing the patient to resume a completely normal life...
October 17, 2018: Drug Discovery Today
https://www.readbyqxmd.com/read/30342245/accomplishments-and-challenges-in-stem-cell-imaging-in-vivo
#13
REVIEW
Rajendran J C Bose, Robert F Mattrey
Stem cell therapies have demonstrated promising preclinical results, but very few applications have reached the clinic owing to safety and efficacy concerns. Translation would benefit greatly if stem cell survival, distribution and function could be assessed in vivo post-transplantation, particularly in patients. Advances in molecular imaging have led to extraordinary progress, with several strategies being deployed to understand the fate of stem cells in vivo using magnetic resonance, scintigraphy, PET, ultrasound and optical imaging...
October 17, 2018: Drug Discovery Today
https://www.readbyqxmd.com/read/30342244/advances-in-particle-shape-engineering-for-improved-drug-delivery
#14
REVIEW
Yiwei Yang, Di Nie, Yuan Liu, Miaorong Yu, Yong Gan
Spherical particles such as liposomes and microspheres are the most common and extensively applied drug vehicles. However, researchers have come to realize the superiority of nonspherical nanoparticles. Actually, in human bodies red blood cells, gut biotics and many well-known pathogens have distinct shapes. It can be reasonably inferred that particle shape plays a pivotal part in human bodies. In this review, we summarize the recent studies about the effect of shape on delivery processes such as cellular uptake, tissue penetration and biodistribution...
October 17, 2018: Drug Discovery Today
https://www.readbyqxmd.com/read/30339822/trends-in-interorganizational-transactions-in-personalized-medicine-development
#15
Tomohiro Makino, Shintaro Sengoku, Shuichi Ishida, Kota Kodama
Personalized medicine is an innovative concept that allows patients with a validated companion diagnosis (CoDx) to receive treatment using the most suitable drug. Currently, a major movement in the pharmaceutical industry involves the integrated use of multiple resources from external sources. To ascertain preferable interorganizational collaborations and their suitable exits, we compared the related transactions in personalized and nonpersonalized cancer drugs. We found that there were significantly more of some alliance deals in personalized medicine, and that market licenses, one of the exits, were well correlated with other alliances only in personalized medicine...
October 16, 2018: Drug Discovery Today
https://www.readbyqxmd.com/read/30315890/targeting-vegf-neuropilin-interactions-a-promising-antitumor-strategy
#16
REVIEW
Kewen Peng, Ying Bai, Qihua Zhu, Bin Hu, Yungen Xu
Inhibition of vascular endothelial growth factor (VEGF) or its corresponding receptor (VEGFR) has been validated as an efficacious antiangiogenetic approach for cancer treatment. More recently, neuropilins (NRPs), the essential coreceptors for VEGF, have also been shown to have a significant role in VEGF signaling. Given the multifaceted effects of VEGF-NRP interactions on tumor initiation and progression, the exploration of new chemical entities that selectively block these interactions has recently attracted considerable interest as a novel antitumor strategy...
October 11, 2018: Drug Discovery Today
https://www.readbyqxmd.com/read/30312743/towards-the-development-of-human-immune-system-on-a-chip-platforms
#17
REVIEW
Alessandro Polini, Loretta L Del Mercato, Adriano Barra, Yu Shrike Zhang, Franco Calabi, Giuseppe Gigli
Organ-on-a-chip (OoCs) platforms could revolutionize drug discovery and might ultimately become essential tools for precision therapy. Although many single-organ and interconnected systems have been described, the immune system has been comparatively neglected, despite its pervasive role in the body and the trend toward newer therapeutic products (i.e., complex biologics, nanoparticles, immune checkpoint inhibitors, and engineered T cells) that often cause, or are based on, immune reactions. In this review, we recapitulate some distinctive features of the immune system before reviewing microfluidic devices that mimic lymphoid organs or other organs and/or tissues with an integrated immune system component...
October 9, 2018: Drug Discovery Today
https://www.readbyqxmd.com/read/30296551/peptide-based-therapeutics-quality-specifications-regulatory-considerations-and-prospects
#18
REVIEW
Shruti Rastogi, Shatrunajay Shukla, M Kalaivani, Gyanendra Nath Singh
Exquisite selectivity, remarkable efficacy, and minimal toxicity are key attributes inherently assigned to peptides, resulting in increased research interest from the pharmaceutical industry in peptide-based therapeutics (PbTs). Pharmacopoeias develop authoritative standards for PbT by providing standard specifications and test methods. Nevertheless, a lack of harmonization in test procedures adopted for PbT in the latest editions of Pharmacopoeias has been observed. Adoption of a harmonized monograph could increase further the interest of the global pharmaceutical industry in PbTs...
October 6, 2018: Drug Discovery Today
https://www.readbyqxmd.com/read/30292917/application-of-nanotechnology-to-improve-the-therapeutic-benefits-of-statins
#19
REVIEW
Shahla Korani, Mitra Korani, Samira Bahrami, Thomas P Johnston, Alexandra E Butler, Maciej Banach, Amirhossein Sahebkar
Hyperlipidemia is defined as an elevated level of lipids and lipoproteins in the blood and is considered to be a significant risk factor for accelerating the process of atherosclerosis and, consequently, cardiovascular disease. The level of cholesterol, especially low-density lipoprotein cholesterol (LDL-C), is commonly elevated in hyperlipidemia and represents the primary therapeutic target. Statins are a group of drugs that function by inhibiting 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase and are extremely efficacious in reducing elevated LDL-C in the serum and preventing atherosclerotic cardiovascular disease...
October 5, 2018: Drug Discovery Today
https://www.readbyqxmd.com/read/30292916/design-strategies-for-chemical-stimuli-responsive-programmable-nanotherapeutics
#20
REVIEW
Muhammad Gulfam, Fitsum Feleke Sahle, Tao L Lowe
Chemical-stimuli-responsive nanotherapeutics have gained great interest in drug delivery and diagnosis applications. These nanotherapeutics are designed to respond to specific internal stimuli including pH, ionic strength, redox, reactive oxygen species, glucose, enzymes, ATP and hypoxia for site-specific and responsive or triggered release of payloads and/or biomarker detections. This review systematically and comprehensively addresses up-to-date technological and design strategies, and challenges nanomaterials to be used for triggered release and sensing in response to chemical stimuli...
October 5, 2018: Drug Discovery Today
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