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Drug Discovery Today

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https://www.readbyqxmd.com/read/28625610/current-progress-in-antivascular-tumor-therapy
#1
REVIEW
Yi-Ju Ho, Tzu-Chia Wang, Ching-Hsiang Fan, Chih-Kuang Yeh
The tumor vasculature transports oxygen, nutrients and drugs for crucial roles in tumor therapy. Antivascular therapy directly targets existing tumor vessels to reduce blood perfusion and then inhibit tumor growth. Vascular disrupting agents and ultrasound-stimulated microbubble destruction use chemical toxicity and physical effect, respectively, to damage vascular endothelial cells for antivascular therapy. Moreover, antivascular therapy can break vessel wall barriers and change the tumor microenvironment to compensate for the limitations of conventional chemotherapy or radiotherapy...
June 15, 2017: Drug Discovery Today
https://www.readbyqxmd.com/read/28624633/from-flamingo-dance-to-desirable-drug-discovery-a-nature-inspired-approach
#2
REVIEW
Aminael Sánchez-Rodríguez, Yunierkis Pérez-Castillo, Stephan C Schürer, Orazio Nicolotti, Giuseppe Felice Mangiatordi, Fernanda Borges, M Natalia D S Cordeiro, Eduardo Tejera, José L Medina-Franco, Maykel Cruz-Monteagudo
The therapeutic effects of drugs are well known to result from their interaction with multiple intracellular targets. Accordingly, the pharma industry is currently moving from a reductionist approach based on a 'one-target fixation' to a holistic multitarget approach. However, many drug discovery practices are still procedural abstractions resulting from the attempt to understand and address the action of biologically active compounds while preventing adverse effects. Here, we discuss how drug discovery can benefit from the principles of evolutionary biology and report two real-life case studies...
June 15, 2017: Drug Discovery Today
https://www.readbyqxmd.com/read/28627386/big-data-analysis-of-global-advances-in-pharmaceutics-and-drug-delivery-1980-2014
#3
REVIEW
Weixiang Zhang, Qianqian Zhao, Junling Deng, Yuanjia Hu, Yitao Wang, Defang Ouyang
The past three decades have witnessed an upsurge of publications in pharmaceutics and the drug delivery field. This review provides a landscape of global research advances in pharmaceutics in the period 1980-2014 from publications, countries and institutions, and their collaborations. The scientific knowledge mapping analysis showed that the research frontier shifted from conventional pharmaceutical techniques (1980-1992) to advanced drug delivery systems (1993-2014). The history of drug delivery for this period is summarized and future prospects of pharmaceutical research are discussed...
June 13, 2017: Drug Discovery Today
https://www.readbyqxmd.com/read/28627385/advances-in-antibody-drug-conjugates-a-new-era-of-targeted-cancer-therapy
#4
REVIEW
Samaresh Sau, Hashem O Alsaab, Sushil Kumar Kashaw, Katyayani Tatiparti, Arun K Iyer
Antibody-drug conjugates (ADCs), a potent class of anticancer therapeutics, comprise a high-affinity antibody (Ab) and cytotoxic payload coupled via a suitable linker for selective tumor cell killing. In the initial phase of their development, two ADCs, Mylotarg(®), and Adcetris(®) were approved by the US Food and Drug Administration (FDA) for treating hematological cancer, but the real breakthrough came with the discovery of the breast cancer-targeting ADC, Kadcyla(®). With advances in bioengineering, linker chemistry, and potent cytotoxic payload, ADC technology has become a more powerful tool for targeted cancer therapy...
June 13, 2017: Drug Discovery Today
https://www.readbyqxmd.com/read/28600191/lipid-polymer-hybrid-nanoparticle-mediated-therapeutics-delivery-advances-and-challenges
#5
REVIEW
Rajendran J C Bose, Rramaswamy Ravikumar, Vengadeshprabu Karuppagounder, Devasier Bennet, Sabarinathan Rangasamy, Rajarajan A Thandavarayan
With rapid advances in nanomedicine, lipid-polymer hybrid nanoparticles (LPHNPs) have emerged as promising nanocarriers for several biomedical applications, including therapeutics delivery and biomedical imaging. Significant research has been dedicated to biomimetic or targeting functionalization, as well as controlled and image-guided drug-release capabilities. Despite this research, the clinical translation of LPHNP-mediated therapeutics delivery has progressed incrementally. In this review, we discuss the recent advances in and challenges to the development and application of LPHNPs, present examples to demonstrate the advantages of LPHNPs in therapeutics delivery and imaging applications, and discuss the translational obstacles to LPHNP technology...
June 7, 2017: Drug Discovery Today
https://www.readbyqxmd.com/read/28600190/understanding-the-checkpoint-blockade-in-lung-cancer-immunotherapy
#6
REVIEW
Maria G Dal Bello, Angela Alama, Simona Coco, Irene Vanni, Francesco Grossi
Immunotherapies have changed the treatment strategy of some types of tumor including melanoma and, more recently, non-small-cell lung cancer (NSCLC). Immune checkpoints are crucial for the maintenance of self-tolerance and it is known that some tumors use checkpoint systems to evade antitumor immune response. The treatment of advanced NSCLC by immune-checkpoint blockade targeting the PD1/PDL1 and CTLA4 pathways has led to significant clinical benefit either as monotherapy or in combination therapy. Moreover, checkpoint receptors such as LAG3, TIM3 and KIRs are also being investigated as potential immunotherapeutic targets...
June 7, 2017: Drug Discovery Today
https://www.readbyqxmd.com/read/28577912/targeting-survivin-for-therapeutic-discovery-past-present-and-future-promises
#7
REVIEW
Robert C Peery, Jing-Yuan Liu, Jian-Ting Zhang
Survivin, the smallest member of the inhibitor of apoptosis protein (IAP) family, is overexpressed in cells of almost all cancers but not in most normal tissues in adults. Survivin expression is required for cancer cell survival and knocking down its expression or inhibiting its function using molecular approaches results in spontaneous apoptosis. Thus, survivin is an attractive and perhaps ideal target for cancer drug discovery. However, a US Food and Drug Administration (FDA)-approved drug targeting survivin has yet to emerge...
May 31, 2017: Drug Discovery Today
https://www.readbyqxmd.com/read/28576430/gastric-bypass-surgery-mimetic-approaches
#8
REVIEW
Brian R Boettcher
Gastric bypass surgery is effectively a polypharmacological approach for treatment of obesity, type 2 diabetes and nonalcoholic steatohepatitis (NASH). The gastric bypass mimetic approaches reviewed are fixed-dose combinatorial pharmacological approaches. There are two key concepts incorporated into these gastric bypass surgery mimetic approaches. The first key concept is that the combination of glucagon-like peptide 1 (GLP-1) and fibroblast growth factor 21 (FGF21) is essential for success of any gastric bypass surgery mimetic approach...
May 30, 2017: Drug Discovery Today
https://www.readbyqxmd.com/read/28552498/electrospun-polymeric-micro-nanofibrous-scaffolds-for-long-term-drug-release-and-their-biomedical-applications
#9
REVIEW
Qiang Zhang, Yingchun Li, Zhi Yuan William Lin, Kenneth K Y Wong, Min Lin, Lara Yildirimer, Xin Zhao
Electrospun polymeric micro/nanofibrous scaffolds have been investigated extensively as drug delivery platforms capable of controlled and sustained release of therapeutic agents in situ. Such scaffolds exhibit excellent physicochemical and biological properties and can encapsulate and release various drugs in a controlled fashion. This article reviews recent advances in the design and manufacture of electrospun scaffolds for long-term drug release, placing particular emphasis on polymer selection, types of incorporated drugs and the latest drug-loading techniques...
May 24, 2017: Drug Discovery Today
https://www.readbyqxmd.com/read/28545838/strategies-for-targeted-drug-delivery-in-treatment-of-colon-cancer-current-trends-and-future-perspectives
#10
REVIEW
Antara Banerjee, Surajit Pathak, Vimala Devi Subramanium, Dharanivasan G, Ramachandran Murugesan, Rama S Verma
Despite advances in treatment modalities, colon cancer (CC) is the third most common cause of cancer-related death worldwide. Subsequent unfavorable effects owing to toxicity of conventional drugs are a challenging problem associated with chemotherapy. There is noticeable concern toward site-specific/targeted delivery of chemotherapeutic drugs specifically to the affected site of the colon in a predictable and reproducible manner. However, the biggest challenge in successful drug targeting for the colon is avoidance of drug absorption and/or degradation in the upper gastrointestinal tract before the drug reaches the colon...
May 22, 2017: Drug Discovery Today
https://www.readbyqxmd.com/read/28545837/emerging-technologies-for-prediction-of-drug-candidate-efficacy-in-the-preclinical-pipeline
#11
Denis Menshykau
The pharmaceutical industry is tackling increasingly complex multifactorial diseases, resulting in increases in research & development (R&D) costs and reductions in the success rates for drug candidates during Phase 2 and 3 clinical trials, with a lack of efficacy being the primary reason for drug candidate failure. This implies that the predictive power of current preclinical assays for drug candidate efficacy is suboptimal and, therefore, that alternatives should be developed. Here, I review emerging in vitro, imaging, and in silico technologies and discuss their potential contribution to drug efficacy assessment...
May 22, 2017: Drug Discovery Today
https://www.readbyqxmd.com/read/28533190/in-vitro-bioassays-to-evaluate-beneficial-and-adverse-health-effects-of-botanicals-promises-and-pitfalls
#12
REVIEW
Gerhard Prinsloo, Georgia Papadi, Mebrahtom G Hiben, Laura de Haan, Jochem Louisse, Karsten Beekmann, Jacques Vervoort, Ivonne M C M Rietjens
This review provides an update on the promises and pitfalls when using in vitro bioassays to evaluate beneficial and adverse health effects of botanicals and botanical preparations. Important issues addressed in the paper are: (i) the type of assays and biological effects available; (ii) false-positives, false-negatives and confounding factors; (iii) matrix and combination effects; (iv) extrapolation of in vitro data to the in vivo situation; (v) when (not) to use bioassays; and (vi) identification of active constituents...
May 19, 2017: Drug Discovery Today
https://www.readbyqxmd.com/read/28533189/potential-therapeutic-effects-of-odorants-through-their-ectopic-receptors-in-pigmented-cells
#13
REVIEW
Barbara Pavan, Antonio Capuzzo, Alessandro Dalpiaz
Several olfactory receptors (ORs) have been characterized outside the olfactory neuroepithelium in neuronal and non-neuronal tissues, where they were implicated in the recognition of diverse chemical signals. ORs have been found to regulate melanogenesis in skin melanocytes, and OR expression has been found in the human brain nigrostriatal dopaminergic neurons, where production of melanin occurs as neuromelanin and can change with age; OR expression is downregulated in Parkinson's disease. Therefore, we propose several odorants as new functional ligands to ORs expressed in non-olfactory pigmented cells as dopaminergic neurons and melanocytes, where, by acting on cAMP-induced melanin production, they could help to counteract melanogenic and neurodegenerative dysfunctions, including melanoma and Parkinson's disease...
May 19, 2017: Drug Discovery Today
https://www.readbyqxmd.com/read/28533188/carbon-nanomaterials-as-versatile-platforms-for-theranostic-applications
#14
REVIEW
Mirae Kim, Jinhyeong Jang, Chaenyung Cha
Theranostic nanomedicine, utilizing state-of-the-art, multifaceted nanomaterials and devices with therapeutic and diagnostic dual functions, has emerged as a highly attractive and promising new field of medicine. The theory behind the use of nanomaterials for theranostic applications is to impart multifunctionality by applying various engineering strategies to combine different modalities on a nanoscale. Carbon nanomaterials, which have been a subject of intense scientific research and industrial applications in recent years, have also found their way into theranostic nanomedicine owing to their innate multifunctionality...
May 19, 2017: Drug Discovery Today
https://www.readbyqxmd.com/read/28533187/host-directed-therapies-offer-novel-opportunities-for-the-fight-against-tuberculosis
#15
REVIEW
Arnaud Machelart, Ok-Ryul Song, Eik Hoffmann, Priscille Brodin
Tuberculosis (TB) remains a leading global health problem that is exacerbated by the emergence of multidrug and extensively drug-resistant Mycobacterium tuberculosis strains. Control of the disease requires novel therapeutic strategies. Modulating host homeostasis appears to be a promising approach, and recent studies have identified novel potential host targets and compounds that could be investigated for host-directed therapies (HDTs). Moreover, the recent development of intracellular high-throughput phenotypic assays makes it possible to screen large libraries of compounds to identify more rapidly new effectors for mycobacterial elimination...
May 19, 2017: Drug Discovery Today
https://www.readbyqxmd.com/read/28526660/magnetic-nanoformulations-for-prostate-cancer
#16
Pallabita Chowdhury, Allison M Roberts, Sheema Khan, Bilal B Hafeez, Subhash C Chauhan, Meena Jaggi, Murali M Yallapu
Magnetic nanoparticles (MNPs) play a vital role for improved imaging applications. Recently, a number of studies demonstrate MNPs can be applied for targeted delivery, sustained release of therapeutics, and hyperthermia. Based on stable particle size and shape, biocompatibility, and inherent contrast enhancement characteristics, MNPs have been encouraged for pre-clinical studies and human use. As a theranostic platform development, MNPs need to balance both delivery and imaging aspects. Thus, this review provides significant insight and advances in the theranostic role of MNPs through the documentation of unique magnetic nanoparticles used in prostate cancer, their interaction with prostate cancer cells, in vivo fate, targeting, and biodistribution...
May 16, 2017: Drug Discovery Today
https://www.readbyqxmd.com/read/28511997/thorough-qt-tqt-studies-concordance-with-torsadogenesis-and-an-evolving-cardiac-safety-testing-paradigm
#17
Barbara Wiśniowska, Zofia Tylutki, Sebastian Polak
Since 2005, when the International Conference on Harmonisation (ICH) E14 guideline was adopted, no drug has been withdrawn because of QTc prolongation or torsade de pointes arrhythmia. There are, however, costs associated with this success. In addition to the time and money invested, thorough QT (TQT) studies have limited the efficiency of the drug development pipeline. In this paper, we discuss the relevance of TQT trials as a tool for proarrhythmic risk prediction as a part of the debate regarding their usefulness...
May 13, 2017: Drug Discovery Today
https://www.readbyqxmd.com/read/28506718/g-quadruplex-surveillance-in-bcl-2-gene-a-promising-therapeutic-intervention-in-cancer-treatment
#18
REVIEW
Pallabi Sengupta, Samit Chattopadhyay, Subhrangsu Chatterjee
BCL-2 overexpression promotes neoplastic cell expansion in cancers. Multiple noncanonical B-DNA motifs in the BCL-2 gene regulate selective modulation of its expression in normal and cancer cells. Three G-quadruplex topologies and one i-motif, in the vicinity of the P1 (major) promoter, stringently control its transcription. RNA quadruplexes and Z-DNA elements within translocation breakpoints of noncoding regions affect translation and promote oncogenic transformation of BCL-2 [e.g., t(14;18) translocation]...
May 12, 2017: Drug Discovery Today
https://www.readbyqxmd.com/read/28487070/noncoding-rna-and-epigenetic-gene-regulation-in-renal-disease
#19
REVIEW
Satya K Kota, Savithri B Kota
Kidneys have a major role in normal physiology and metabolic homeostasis. Loss or impairment of kidney function is a common occurrence in several metabolic disorders, including hypertension and diabetes. Chronic kidney disease (CKD) affect nearly 10% of the population worldwide; ranks 18th in the list of causes of death; and contributes to a significant proportion of healthcare costs. The tissue repair and regenerative potential of kidneys are limited and they decline during aging. Recent studies have demonstrated a key role for epigenetic processes and players, such as DNA methylation, histone modifications, noncoding (nc)RNA, and so on, in both kidney development and disease...
May 6, 2017: Drug Discovery Today
https://www.readbyqxmd.com/read/28487069/development-of-nanomaterials-for-bone-targeted-drug-delivery
#20
REVIEW
Hao Cheng, Aditya Chawla, Yafeng Yang, Yuxiao Li, Jin Zhang, Hae Lin Jang, Ali Khademhosseini
Bone is one of the major organs of the human body; it supports and protects other organs, produces blood cells, stores minerals, and regulates hormones. Therefore, disorders in bone can cause serious morbidity, complications, or mortality of patients. However, despite the significant occurrence of bone diseases, such as osteoarthritis (OA), osteoporosis (OP), non-union bone defects, bone cancer, and myeloma-related bone disease, their effective treatments remain a challenge. In this review, we highlight recent progress in the development of nanotechnology-based drug delivery for bone treatment, based on its improved delivery efficiency and safety...
May 6, 2017: Drug Discovery Today
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