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https://www.readbyqxmd.com/read/28098746/marine-antibody-drug-conjugates-design-strategies-and-research-progress
#1
REVIEW
Yu-Jie Wang, Yu-Yan Li, Xiao-Yu Liu, Xiao-Ling Lu, Xin Cao, Bing-Hua Jiao
Antibody-drug conjugates (ADCs), constructed with monoclonal antibodies (mAbs), linkers, and natural cytotoxins, are innovative drugs developed for oncotherapy. Owing to the distinctive advantages of both chemotherapy drugs and antibody drugs, ADCs have obtained enormous success during the past several years. The development of highly specific antibodies, novel marine toxins' applications, and innovative linker technologies all accelerate the rapid R&D of ADCs. Meanwhile, some challenges remain to be solved for future ADCs...
January 13, 2017: Marine Drugs
https://www.readbyqxmd.com/read/28095674/the-century-of-biology-and-the-evolving-role-of-medicinal-chemists-in-neuroscience
#2
Dario Doller
Society expects that the wave of contemporary new discoveries in biological sciences will soon lead to novel treatments for human diseases, including many devastating brain disorders. Historically, medicinal chemists have contributed to drug discovery teams in ways that synergize with those from their partner sciences, and help transform new knowledge into the ultimate tangible asset: a new drug. The optimal balance of resources and the right strategy to minimize the risk of late clinical failure may differ for different therapeutic indications...
January 18, 2017: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/28088572/bcs-class-iv-drugs-highly-notorious-candidates-for-formulation-development
#3
REVIEW
Rohan Ghadi, Neha Dand
BCS class IV drugs (e.g., amphotericin B, furosemide, acetazolamide, ritonavir, paclitaxel) exhibit many characteristics that are problematic for effective oral and per oral delivery. Some of the problems associated include low aqueous solubility, poor permeability, erratic and poor absorption, inter and intra subject variability and significant positive food effect which leads to low and variable bioavailability. Also, most of the class IV drugs are substrate for P-glycoprotein (low permeability) and substrate for CYP3A4 (extensive pre systemic metabolism) which further potentiates the problem of poor therapeutic potential of these drugs...
January 11, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/28076854/open-angle-glaucoma-drug-development-pipeline-during-the-last-20-years-1995-2015
#4
André Vicente, Sylvie Prud'homme, Joana Ferreira, Luís Abegão Pinto, Ingeborg Stalmans
OBJECTIVES: To analyse drug development for open-angle glaucoma during the last 20 years. METHODS: Research was performed by referring to clinical trials registered at the International Clinical Trials Registry Platform (ICTRP). A search for the condition "open-angle glaucoma" with the intervention "drug" was performed. We included trials registered from 01/01/1995 to 01/01/2015, only involving studies in phases 1, 2, and 3. Only studies resorting to novel treatment strategies (either novel drugs or yet-untested fixed associations of approved medication) were considered...
January 12, 2017: Ophthalmic Research
https://www.readbyqxmd.com/read/28069987/transgenic-zebrafish-reporter-lines-as-alternative-in-vivo-organ-toxicity-models
#5
Kar Lai Poon, Xingang Wang, Serene Gp Lee, Ashley S Ng, Wei Huang Goh, Zhonghua Zhao, Muthafar Al-Haddawi, Haishan Wang, Sinnakaruppan Mathavan, Phillip W Ingham, Claudia Mcginnis, Tom J Carney
Organ toxicity, particularly liver toxicity, remains one of the major reasons for termination of drug candidates in the development pipeline as well as withdrawal or restrictions of marketed drugs. A screening-amenable alternative in vivo model such as zebrafish would therefore find immediate application in the early prediction of unacceptable organ toxicity. To identify highly upregulated genes as biomarkers of toxic responses in the zebrafish model, a set of well-characterized reference drugs that cause drug induced liver injury (DILI) in the clinic were applied to zebrafish larvae and adults...
January 9, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/28067172/fusing-docking-scoring-functions-improves-the-virtual-screening-performance-for-discovering-parkinson-s-disease-dual-target-ligands
#6
Yunierkis Perez-Castillo, Aliuska Morales Helguera, M Natália D S Cordeiro, Eduardo Tejera, Cesar Paz-Y-Miño, Aminael Sánchez-Rodríguez, Fernanda Borges, Maykel Cruz-Monteagudo
Virtual methodologies have become essential components of the drug discovery pipeline. Specifically, structure-based drug design methodologies exploit the 3D structure of molecular targets to discover new drug candidates through molecular docking. Recently, dual target ligands of the Adenosine A2A Receptor and Monoamine Oxidase B enzyme have been proposed as effective therapies for the treatment of Parkinson's disease. To the best of our knowledge, no theoretical study has been devoted to developing structure-based virtual screening methodologies for the discovery of dual A2AAR antagonists and MAO-B inhibitors...
January 9, 2017: Current Neuropharmacology
https://www.readbyqxmd.com/read/28059955/diagnosis-of-opportunistic-infections-hiv-co-infections-tuberculosis
#7
Lesley Scott, Pedro da Silva, Catharina C Boehme, Wendy Stevens, Chris Gilpin
PURPOSE OF REVIEW: Tuberculosis (TB) incidence has declined ∼1.5% annually since 2000, but continued to affect 10.4 million individuals in 2015, with 1/3 remaining undiagnosed or underreported. The diagnosis of TB among those co-infected with HIV is challenging as TB remains the leading cause of death in such individuals. Accurate and rapid diagnosis of active TB will avert mortality in both adults and children, reduce transmission, and assist in timeous decisions for antiretroviral therapy initiation...
January 5, 2017: Current Opinion in HIV and AIDS
https://www.readbyqxmd.com/read/28057848/a-pipeline-for-drug-target-identification-and-validation
#8
Eusebio Manchado, Chun-Hao Huang, Nilgun Tasdemir, Darjus F Tschaharganeh, John E Wilkinson, Scott W Lowe
Rapid and affordable tumor profiling has led to an explosion of genomic data that is facilitating the development of new cancer therapies. The potential of therapeutic strategies aimed at inactivating the oncogenic lesions that contribute to the aberrant survival and proliferation of tumor cells has yielded remarkable success in some malignancies such as BRAF-mutant melanoma and BCR-ABL expressing chronic myeloid leukemia. However, the direct inhibition of several well-established oncoproteins in some of these cancers is not possible or produces only transient benefits...
January 5, 2017: Cold Spring Harbor Symposia on Quantitative Biology
https://www.readbyqxmd.com/read/28053072/the-promise-of-new-technologies-to-reduce-refine-or-replace-animal-use-while-reducing-risks-of-drug-induced-liver-injury-in-pharmaceutical-development
#9
Frank D Sistare, William B Mattes, Edward L LeCluyse
Drug induced liver injury (DILI) has contributed more to marketed pharmaceutical withdrawals and clinical development failures than any other human organ toxicity. DILI seen in animal studies also frequently leads to the discontinuation of promising drug candidates very early in the pipeline. This manuscript reviews and critically assesses the current regulatory expectations; the current drug development approaches, strategies, and gaps; and the numerous exciting opportunities becoming available to address these gaps through technological advances...
December 2016: ILAR Journal
https://www.readbyqxmd.com/read/28049605/liquid-chromatography-coupled-with-tandem-mass-spectrometry-lc-ms-ms-based-bioavailability-determination-of-the-major-classes-of-phytochemicals
#10
Evgenios Stylos, Maria V Chatziathanasiadou, Aggeliki Syriopoulou, Andreas G Tzakos
Natural products derived from plants have served as an inexhausted source for drug discovery and drug development. They have been evolutionary amplified with drug-like properties and have already illustrated immense therapeutic potential over an array of different diseases. However, their incorporation in the drug discovery pipeline has been diminished the last two decades. This was probably due to barriers related to their inherent difficulties to be integrated in high-throughput screening assays as also their largely unexplored bioavailability...
December 20, 2016: Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences
https://www.readbyqxmd.com/read/28043590/use-of-wgs-in-mycobacterium-tuberculosis-routine-diagnosis
#11
Daniela M Cirillo, Andrea M Cabibbe, Maria Rosaria De Filippo, Alberto Trovato, Tullia Simonetti, Gian Maria Rossolini, Enrico Tortoli
OBJECTIVE/BACKGROUND: Whole Genome Sequencing (WGS) is becoming affordable with overall costs comparable to other tests currently in use to perform the diagnosis of drug-resistant tuberculosis (TB) and cluster analysis. The WGS approach allows an "all-in-one" approach providing results on expected sensitivity of the strains, genetic background, epidemiological data, and indication of risk of laboratory cross-contamination. METHODS: Although ideal, WGS from the direct diagnostic specimen is not yet standardized, and to date the two most promising approaches are WGS from early positive liquid culture and targeted sequencing from diagnostic specimens using Next-Generation Technology...
December 2016: International Journal of Mycobacteriology
https://www.readbyqxmd.com/read/28043559/host-directed-therapies-for-multidrug-resistant-tuberculosis
#12
Alimuddin Zumla, Markus Maeurer
Tuberculosis (TB) causes 1.3 million deaths annually. There are 0.5 million cases of multidrug resistant TB (MDR-TB) and the number of cases is rising globally. The current status quo of the lengthy treatment duration and poor treatment outcomes associated with MDR/extensively drug-resistant TB, and those with comorbidity of TB with human immunodeficiency virus and noncommunicable diseases in sub-Saharan Africa is unacceptable. The TB drug pipeline remains sparse. New innovations for shortening the duration of therapy and improving treatment outcomes (cure and long-term functional disability due to lung damage) are urgently required...
December 2016: International Journal of Mycobacteriology
https://www.readbyqxmd.com/read/28039165/pbit-pipeline-builder-for-identification-of-drug-targets-for-infectious-diseases
#13
Gauri Shende, Harshala Haldankar, Ram Shankar Barai, Mohammed Husain Bharmal, Vinit Shetty, Susan Idicula-Thomas
: PBIT (Pipeline Builder for Identification of drug Targets) is an online webserver that has been developed for screening of microbial proteomes for critical features of human drug targets such as being non-homologous to human proteome as well as the human gut microbiota, essential for the pathogen's survival, participation in pathogen-specific pathways etc. The tool has been validated by analyzing 57 putative targets of Candida albicans documented in literature. PBIT integrates various in silico approaches known for drug target identification and will facilitate high-throughput prediction of drug targets for infectious diseases, including multi-pathogenic infections...
December 30, 2016: Bioinformatics
https://www.readbyqxmd.com/read/28035197/evolving-new-strategies-for-the-medical-management-of-chronic-hepatitis-b-virus-infection
#14
Timothy M Block, Tianlun Zhou, Nikhil Anbarasan, Robert Gish
Is a cure for chronic hepatitis B virus (HBV) infection possible? Hepatitis C virus infection is now routinely cured medically. There is a growing expectation that new drugs for the management of chronic HBV infection should provide substantial benefit over and above that of current chronic HBV medications, if not be curative. Although the definition of medically induced cure for chronic HBV infection varies, most include sustained off-drug absence of viremia and negativity for other virologic markers. There are currently more than 29 drugs in the pipeline being tested for the management of chronic HBV infection...
November 2016: Gastroenterology & Hepatology
https://www.readbyqxmd.com/read/28034810/prevalence-and-incidence-of-drug-resistant-mesial-temporal-lobe-epilepsy-in-the-united-states
#15
REVIEW
Ali A Asadi-Pooya, Gregory R Stewart, Daniel J Abrams, Ashwini Sharan
OBJECTIVE: We reviewed data on the epidemiology of epilepsy in the United States and estimated the prevalence and incidence of drug-resistant temporal lobe epilepsy (TLE) due to hippocampal sclerosis (HS) based on extrapolation from the available data drawn from the literature. METHODS: We searched the electronic database PubMed on December 14, 2016 using the following search terms in the title: "epilepsy" OR "temporal lobe" OR "hippocampal sclerosis" AND "epidemiology" OR "prevalence" OR "incidence"...
December 26, 2016: World Neurosurgery
https://www.readbyqxmd.com/read/28025919/amcp-partnership-forum-enabling-the-exchange-of-clinical-and-economic-information-pre-fda-approval
#16
(no author information available yet)
: Current federal laws and FDA regulations have significantly restricted the sharing of clinical and health economic information on biopharmaceuticals that have yet to receive FDA approval. Over the past several years, organizations that make health care coverage decisions, including those that set copayments, premiums, and formulary placement, have expressed a need for receiving this information before approval, as long as appropriate safeguards exist to prevent this information from reaching unintended entities...
January 2017: Journal of Managed Care & Specialty Pharmacy
https://www.readbyqxmd.com/read/28024400/cheminformatics-modeling-of-adverse-drug-responses-by-clinically-relevant-mutants-of-human-androgen-receptor
#17
Naman Paul, Lavinia A Carabet, Nada Lallous, Takeshi Yamazaki, Martin E Gleave, Paul S Rennie, Artem Cherkasov
The human androgen receptor (AR) is a ligand-activated transcription factor that plays a pivotal role in the development and progression of prostate cancer (PCa). Many forms of castration-resistant prostate cancer (CRPC) still rely on the AR for survival. Currently used antiandrogens face clinical limitations as drug resistance develops in patients over time since they all target the mutation-prone androgen binding site (ABS), where gain-of-function mutations eventually convert antagonists into agonists. With a significant number of reported distinct mutations located across the ABS, it is imperative to develop a prognostic platform which would equip clinicians with prior knowledge and actionable strategies if cases of previously unreported AR mutations are encountered...
December 27, 2016: Journal of Chemical Information and Modeling
https://www.readbyqxmd.com/read/28018986/a-roadmap-for-the-development-of-applied-computational-psychiatry
#18
Martin P Paulus, Quentin J M Huys, Tiago V Maia
BACKGROUND: Computational psychiatry is a burgeoning field that utilizes mathematical approaches to investigate psychiatric disorders, derive quantitative predictions, and integrate data across multiple levels of description. Computational psychiatry has already led to many new insights into the neurobehavioral mechanisms that underlie several psychiatric disorders, but its usefulness from a clinical standpoint is only now starting to be considered. METHODS: Examples of computational psychiatry are highlighted, and a phase-based pipeline for the development of clinical computational-psychiatry applications is proposed, similar to the phase-based pipeline used in drug development...
September 2016: Biological Psychiatry: Cognitive Neuroscience and Neuroimaging
https://www.readbyqxmd.com/read/28017531/recent-advancements-in-the-development-of-anti-tuberculosis-drugs
#19
REVIEW
Sarentha Chetty, Muthusamy Ramesh, Ashona Singh-Pillay, Mahmoud E S Soliman
Modern chemotherapy has significantly improved patient outcomes against drug-sensitive tuberculosis. However, the rapid emergence of drug-resistant tuberculosis, together with the bacterium's ability to persist and remain latent present a major public health challenge. To overcome this problem, research into novel anti-tuberculosis targets and drug candidates is thus of paramount importance. This review article provides an overview of tuberculosis highlighting the recent advances and tools that are employed in the field of anti-tuberculosis drug discovery...
November 29, 2016: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28013025/an-automated-assay-for-the-assessment-of-cardiac-arrest-in-fish-embryo
#20
Elodie Puybareau, Diane Genest, Emilie Barbeau, Marc Léonard, Hugues Talbot
Studies on fish embryo models are widely developed in research. They are used in several research fields including drug discovery or environmental toxicology. In this article, we propose an entirely automated assay to detect cardiac arrest in Medaka (Oryzias latipes) based on image analysis. We propose a multi-scale pipeline based on mathematical morphology. Starting from video sequences of entire wells in 24-well plates, we focus on the embryo, detect its heart, and ascertain whether or not the heart is beating based on intensity variation analysis...
December 15, 2016: Computers in Biology and Medicine
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