keyword
MENU ▼
Read by QxMD icon Read
search

drug R&D

keyword
https://www.readbyqxmd.com/read/28102767/synthesis-stereochemical-characterization-and-antimicrobial-evaluation-of-a-potentially-nonnephrotoxic-3-c-acethydrazide-puromycin-analog
#1
Josh Carter, Blair A Weaver, Maria A Chiacchio, Amy R Messersmith, Will E Lynch, Brent D Feske, Giuseppe Gumina
Puromycin is a peptidyl nucleoside endowed with significant antibiotic and anticancer properties, but also with an unfortunate nephrotoxic character that has hampered its use as a chemotherapeutic agent. Since hydrolysis of puromycin's amide to puromycin aminonucleoside is the first metabolic step leading to nephrotoxicity, we designed a 3'-C-hydrazide analog where the nitrogen and carbon functionality around the amide carbonyl of puromycin are inverted. The title compound, synthesized in 11 steps from D-xylose, cannot be metabolized to the nephrotoxic aminonucleoside...
January 19, 2017: Nucleosides, Nucleotides & Nucleic Acids
https://www.readbyqxmd.com/read/28102520/us-fda-perspective-on-elbasvir-grazoprevir-treatment-for-patients-with-chronic-hepatitis-c-virus-genotype-1-or-4-infection
#2
Sarita D Boyd, LaRee Tracy, Takashi E Komatsu, Patrick R Harrington, Prabha Viswanathan, Jeff Murray, Adam Sherwat
Elbasvir/grazoprevir demonstrated high sustained virologic response rates 12 weeks after the end of treatment (SVR12) across five clinical trials in subjects infected with chronic hepatitis C virus (HCV) genotype 1, including those with advanced chronic kidney disease (CKD), and GT4. Despite favorable results overall, the US Food and Drug Administration (FDA) encountered challenging regulatory issues due to the limitations of clinical trial data in certain subpopulations. In GT1a-infected subjects, baseline NS5A resistance-associated polymorphisms emerged as the strongest baseline characteristic associated with diminished SVR12 rates following 12 weeks of elbasvir/grazoprevir treatment...
January 19, 2017: Clinical Drug Investigation
https://www.readbyqxmd.com/read/28101955/prescription-drug-monitoring-programs-produce-a-limited-impact-on-painkiller-prescribing-in-medicare-part-d
#3
Courtney R Yarbrough
OBJECTIVE: To measure the impact of prescription drug monitoring programs (PDMPs) on prescribing of opioid and nonopioid painkillers. DATA SOURCE: 2010-2013 physician-level Medicare Part D prescribing data released by the Centers for Medicare and Medicaid Services and Propublica. STUDY DESIGN: Using difference-in-differences models with physician-level fixed effects, the study compares prescribing in states with and without PDMPs for opioid and nonopioid analgesics, oxycodone, hydrocodone, and opioids by controlled substances Schedules II-IV...
January 18, 2017: Health Services Research
https://www.readbyqxmd.com/read/28098746/marine-antibody-drug-conjugates-design-strategies-and-research-progress
#4
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/28096166/the-role-of-renal-drug-exposure-in-polymyxin-b-induced-nephrotoxicity
#5
Pooja Manchandani, Jian Zhou, Jessica T Babic, Kimberly R Ledesma, Luan D Truong, Vincent H Tam
Despite dose-limiting nephrotoxic potentials, polymyxin B has re-emerged as the last line of therapy against multidrug-resistant Gram-negative bacterial infections. However, the handling of polymyxin B by the kidneys is still not thoroughly understood. The objectives of this study were to evaluate the impact of renal polymyxin B exposure on nephrotoxicity and to explore the role of megalin in renal drug accumulation. Sprague-Dawley rats (225-250 g) were divided into 3 dosing groups, and polymyxin B was administered (5 mg/kg, 10 mg/kg and 20 mg/kg) subcutaneously once daily...
January 17, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28095572/development-of-a-clinical-pathway-for-atopic-dermatitis-patients-a-case-based-approach
#6
Lyn C Guenther, Anneke Andriessen, Charles W Lynde, John W P Toole, Gary R Sibbald, James N Bergman, Marc Bourcier, Ian D R Landells
BACKGROUND: Atopic dermatitis (AD) is a common chronic skin condition, associated with significant patient morbidity. There are a myriad of excellent evidenced based guidelines to guide clinicians by an extensive review of all the available treatments. However, while well written and complete these papers may not always allow easy transition to clinical application. OBJECTIVE: The purpose of this paper was to develop a practical case-based approach for the treatment and maintenance of AD, enabling translation of guidelines into clinical care...
December 1, 2016: Journal of Drugs in Dermatology: JDD
https://www.readbyqxmd.com/read/28095040/consensus-statement-by-the-american-association-of-clinical-endocrinologists-and-american-college-of-endocrinology-on-the-comprehensive-type-2-diabetes-management-algorithm-2017-executive-summary
#7
Alan J Garber, Martin J Abrahamson, Joshua I Barzilay, Lawrence Blonde, Zachary T Bloomgarden, Michael A Bush, Samuel Dagogo-Jack, Ralph A DeFronzo, Daniel Einhorn, Vivian A Fonseca, Jeffrey R Garber, W Timothy Garvey, George Grunberger, Yehuda Handelsman, Irl B Hirsch, Paul S Jellinger, Janet B McGill, Jeffrey I Mechanick, Paul D Rosenblit, Guillermo E Umpierrez
EXECUTIVE SUMMARY This algorithm for the comprehensive management of persons with type 2 diabetes (T2D) was developed to provide clinicians with a practical guide that considers the whole patient, their spectrum of risks and complications, and evidence-based approaches to treatment. It is now clear that the progressive pancreatic beta-cell defect that drives the deterioration of metabolic control over time begins early and may be present before the diagnosis of diabetes (1). In addition to advocating glycemic control to reduce microvascular complications, this document highlights obesity and prediabetes as underlying risk factors for the development of T2D and associated macrovascular complications...
January 17, 2017: Endocrine Practice
https://www.readbyqxmd.com/read/28094550/pharmacophore-modelling-atom-based-3d-qsar-generation-and-virtual-screening-of-molecules-projected-for-mpges-1-inhibitory-activity
#8
S Misra, M Saini, H Ojha, D Sharma, K Sharma
COX-2 inhibitors exhibit anticancer effects in various cancer models but due to the adverse side effects associated with these inhibitors, targeting molecules downstream of COX-2 (such as mPGES-1) has been suggested. Even after calls for mPGES-1 inhibitor design, to date there are only a few published inhibitors targeting the enzyme and displaying anticancer activity. In the present study, we have deployed both ligand and structure-based drug design approaches to hunt novel drug-like candidates as mPGES-1 inhibitors...
January 17, 2017: SAR and QSAR in Environmental Research
https://www.readbyqxmd.com/read/28094219/3-4-dihydropyrimidinone-coumarin-analogues-as-a-new-class-of-selective-agent-against-s-aureus-synthesis-biological-evaluation-and-molecular-modelling-study
#9
Nirmala S Naik, Lokesh A Shastri, Shrinivas D Joshi, Sheshagiri R Dixit, Bahubali M Chougala, S Samundeeswari, Megharaj Holiyachi, Farzanabi Shaikh, Jyoti Madar, Rashmi Kulkarni, Vinay Sunagar
Bacterial infections are increasingly difficult to combat as bacteria evolve resistance to antibiotic drugs and have severely compromised the arsenal of antibiotic drugs. On the other hand matrix metalloproteinases (MMPs) play a fundamental role in inflammation and extracellular matrix degradation in physiological and pathological conditions. In search of potent antibiotic, taking coumarin and dihydropyrimidinone as lead compound, a green, eco-friendly and efficient protocol has been developed and synthesized the dihydropyrimidin-2(1H)-one/thione derivatives of coumarin 3/4 from substituted 4-formylcoumarins 2 and ethylacetoacetate using urea/thiourea in the presence of catalytic amount of ceric ammonium nitrate is reported...
January 5, 2017: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/28093634/international-osteoporosis-foundation-and-european-calcified-tissue-society-working-group-recommendations-for-the-screening-of-adherence-to-oral-bisphosphonates
#10
A Diez-Perez, K E Naylor, B Abrahamsen, D Agnusdei, M L Brandi, C Cooper, E Dennison, E F Eriksen, D T Gold, N Guañabens, P Hadji, M Hiligsmann, R Horne, R Josse, J A Kanis, B Obermayer-Pietsch, D Prieto-Alhambra, J-Y Reginster, R Rizzoli, S Silverman, M C Zillikens, R Eastell
: Adherence to oral bisphosphonates is low. A screening strategy is proposed based on the response of biochemical markers of bone turnover after 3 months of therapy. If no change is observed, the clinician should reassess the adherence to the treatment and also other potential issues with the drug. INTRODUCTION: Low adherence to oral bisphosphonates is a common problem that jeopardizes the efficacy of treatment of osteoporosis. No clear screening strategy for the assessment of compliance is widely accepted in these patients...
January 16, 2017: Osteoporosis International
https://www.readbyqxmd.com/read/28092656/influence-of-node-abundance-on-signaling-network-state-and-dynamics-analyzed-by-mass-cytometry
#11
Xiao-Kang Lun, Vito R T Zanotelli, James D Wade, Denis Schapiro, Marco Tognetti, Nadine Dobberstein, Bernd Bodenmiller
Signaling networks are key regulators of cellular function. Although the concentrations of signaling proteins are perturbed in disease states, such as cancer, and are modulated by drug therapies, our understanding of how such changes shape the properties of signaling networks is limited. Here we couple mass-cytometry-based single-cell analysis with overexpression of tagged signaling proteins to study the dependence of signaling relationships and dynamics on protein node abundance. Focusing on the epidermal growth factor receptor (EGFR) signaling network in HEK293T cells, we analyze 20 signaling proteins during a 1-h EGF stimulation time course using a panel of 35 antibodies...
January 16, 2017: Nature Biotechnology
https://www.readbyqxmd.com/read/28092143/human-leucocyte-antigen-adverse-drug-reaction-associations-from-a-perspective-of-ethnicity
#12
REVIEW
G S Ghattaoraya, D Middleton, E J M Santos, R Dickson, A R Jones, A Alfirevic
Whilst immune-mediated adverse drug reactions (ADRs) are rare, they are potentially life-threatening and present a major problem for clinicians. The underlying mechanisms that cause ADRs are not fully understood although genomewide association studies (GWAS) and case-control investigations have associated human leucocyte antigen (HLA) alleles as risk factors. There is evidence that a patient's ethnic background can have an impact on their risk of developing an ADR. This review summarizes the evidence related to HLA alleles and ADRs with particular focus on patient ethnicity...
February 2017: International Journal of Immunogenetics
https://www.readbyqxmd.com/read/28091356/resistance-to-gastrointestinal-parasite-infection-in-djallonk%C3%A3-sheep
#13
A Traoré, D R Notter, A Soudre, A Kaboré, I Álvarez, I Fernández, M Sanou, M Shamshuddin, K Periasamy, H H Tamboura, F Goyache
Gastrointestinal parasitism places serious constraints on small ruminant production. The situation has been exacerbated by development of drug resistance in many parasite populations, leading to interest in identification of animals with genetically mediated resistance or tolerance to nematode infections. This study assessed the response to natural infection with gastrointestinal nematodes (GIN) in Djallonké sheep during the rainy season in the Sudan-Guinea Savannah region of Burkina Faso. Haemonchus contortus is the most prevalent GIN at this site and time...
January 16, 2017: Animal: An International Journal of Animal Bioscience
https://www.readbyqxmd.com/read/28090646/influence-of-p-glycoprotein-on-the-disposition-of-fexofenadine-and-its-enantiomers
#14
Fei Li, Karyn D Howard, Michael J Myers
OBJECTIVES: P-glycoprotein (P-gp) is responsible for the efflux of a broad variety of human and veterinary drugs. Canine P-gp polymorphisms alter drug disposition and toxicity, but their impact on the disposition of enantiomeric drugs is unknown. Using fexofenadine as a model compound, we developed and validated HPLC-fluorescence methods to determine the effect of P-gp on the disposition of fexofenadine and its enantiomers. METHODS: A chiral CD-Ph column was used for the separation of (R) and (S)-fexofenadine...
January 16, 2017: Journal of Pharmacy and Pharmacology
https://www.readbyqxmd.com/read/28090612/quantum-chemical-study-and-isothermal-titration-calorimetry-of-%C3%AE-cyclodextrin-complexes-with-mianserin-in-aqueous-solution
#15
Anna Ignaczak, Bartłomiej Pałecz, Sylwia Belica-Pacha
β-Cyclodextrin (β-CD) is studied as a carrier of the drug mianserin (MIA). β-CD with MIA adducts with 1 : 1 and 2 : 1 stoichiometry are investigated in vacuo and in water using quantum chemical methods: PM6 and B3LYP/6-31G(d,p). An effect of the dispersion correction GD2 and the basis set superposition error on the complexation energies is also evaluated. Additionally, the interaction between MIA hydrochloride and β-CD in aqueous solution at 298.15 K is examined experimentally by isothermal titration calorimetry...
January 16, 2017: Organic & Biomolecular Chemistry
https://www.readbyqxmd.com/read/28090431/a-role-for-3d-printing-in-kidney-on-a-chip-platforms
#16
Ryan D Sochol, Navin R Gupta, Joseph V Bonventre
The advancement of "kidney-on-a-chip" platforms - submillimeter-scale fluidic systems designed to recapitulate renal functions in vitro - directly impacts a wide range of biomedical fields, including drug screening, cell and tissue engineering, toxicity testing, and disease modelling. To fabricate kidney-on-a-chip technologies, researchers have primarily adapted traditional micromachining techniques that are rooted in the integrated circuit industry; hence the term, "chip." A significant challenge, however, is that such methods are inherently monolithic, which limits one's ability to accurately recreate the geometric and architectural complexity of the kidney in vivo...
March 2016: Current Transplantation Reports
https://www.readbyqxmd.com/read/28089889/myc-drives-progression-of-small-cell-lung-cancer-to-a-variant-neuroendocrine-subtype-with-vulnerability-to-aurora-kinase-inhibition
#17
Gurkan Mollaoglu, Matthew R Guthrie, Stefanie Böhm, Johannes Brägelmann, Ismail Can, Paul M Ballieu, Annika Marx, Julie George, Christine Heinen, Milind D Chalishazar, Haixia Cheng, Abbie S Ireland, Kendall E Denning, Anandaroop Mukhopadhyay, Jeffery M Vahrenkamp, Kristofer C Berrett, Timothy L Mosbruger, Jun Wang, Jessica L Kohan, Mohamed E Salama, Benjamin L Witt, Martin Peifer, Roman K Thomas, Jason Gertz, Jane E Johnson, Adi F Gazdar, Robert J Wechsler-Reya, Martin L Sos, Trudy G Oliver
Loss of the tumor suppressors RB1 and TP53 and MYC amplification are frequent oncogenic events in small cell lung cancer (SCLC). We show that Myc expression cooperates with Rb1 and Trp53 loss in the mouse lung to promote aggressive, highly metastatic tumors, that are initially sensitive to chemotherapy followed by relapse, similar to human SCLC. Importantly, MYC drives a neuroendocrine-low "variant" subset of SCLC with high NEUROD1 expression corresponding to transcriptional profiles of human SCLC. Targeted drug screening reveals that SCLC with high MYC expression is vulnerable to Aurora kinase inhibition, which, combined with chemotherapy, strongly suppresses tumor progression and increases survival...
December 31, 2016: Cancer Cell
https://www.readbyqxmd.com/read/28088971/-eltrombopag-for-refractory-thrombocytopenia-in-patients-with-allogeneic-hematopoietic-stem-cell-transplantation
#18
Y R Ma, X J Huang, X D Mo, W Han, C H Yan, Y Chen, Y Ji, Y Y Chen, Y Wang, X H Zhang, K Y Liu, L P Xu
Objective: To evaluate the efficacy and safety of eltrombopag in post-HSCT thrombocytopenia. Methods: A total of 10 patients who underwent post-HSCT thrombocytopenia at Peking University center, who had been treated with eltrombopag, were retrospectively evaluated. Results: Of the 10 cases, 5 males and 5 females with a median of 34 years old (range, 17-54 years), 5 patients were acute myeloid leukemia, 3 with acute lymphoid leukemia and 2 with severe aplastic anemia. Nine patients had undergone haplo-identical donor transplantation, and one patient was a matched related recipient...
December 14, 2016: Zhonghua Xue Ye Xue za Zhi, Zhonghua Xueyexue Zazhi
https://www.readbyqxmd.com/read/28088864/an-integrated-high-throughput-multi-omics-platform-enables-data-driven-construction-of-cellular-responses-and-reveals-global-drug-mechanisms-of-action
#19
Jeremy L Norris, Melissa A Farrow, Danielle B Gutierrez, Lauren D Palmer, Nicole Muszynski, Stacy D Sherrod, James C Pino, Jamie L Allen, Jeffrey M Spraggins, Alex L R Lubbock, Ashley T Jordan, William Burns, James C Poland, Carrie E Romer, M Lisa Manier, Yuan-Wei Nei, Boone M Prentice, Kristie L Rose, Salisha Hill, Raf Van de Plas, Tina Tsui, Nathaniel M Braman, M Ray Keller, Stacey A Rutherford, Nichole A Lobdell, Carlos F Lopez, D Borden Lacy, John A McLean, John Peter Wikswo, Eric P Skaar, Richard M Caprioli
An understanding of how cells respond to perturbation is essential for biological applications; however, most approaches for profiling cellular response are limited in scope to pre-established targets. Global analysis of molecular mechanism will advance our understanding of the complex networks constituting cellular perturbation and lead to advancements in areas, such as infectious disease pathogenesis, developmental biology, pathophysiology, pharmacology, and toxicology. We have developed a high-throughput multi-omics platform for comprehensive, de novo characterization of cellular mechanisms of action...
January 14, 2017: Journal of Proteome Research
https://www.readbyqxmd.com/read/28088197/production-of-human-pro-relaxin-h2-in-the-yeast-pichia-pastoris
#20
D Cimini, K Della Corte, R Finamore, L Andreozzi, A Stellavato, A V A Pirozzi, F Ferrara, R Formisano, M De Rosa, M Chino, L Lista, A Lombardi, V Pavone, C Schiraldi
BACKGROUND: Initially known as the reproductive hormone, relaxin was shown to possess other therapeutically useful properties that include extracellular matrix remodeling, anti-inflammatory, anti-ischemic and angiogenic effects. All these findings make relaxin a potential drug for diverse medical applications. Its precursor, pro-relaxin, is an 18 kDa protein, that shows activity in in vitro assays. Since extraction of relaxin from animal tissues raises several issues, prokaryotes and eukaryotes were both used as expression systems for recombinant relaxin production...
January 14, 2017: BMC Biotechnology
keyword
keyword
3428
1
2
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read
×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"