Scientific Program

Day 1

KEYNOTE SPEAKERS
  • Drug Discovery Informatics for Collaborative Teams: Innovations Available Today and Planned for Tomorrow

    collaborative Drug Discovery
    USA
    Abstract

    Collaborative Drug Discovery (CDD) provides trailing innovation for today’s chemical and biological data needs, differentiated by ease-of-use and superior collaborative data sharing workflows. Within the CDD vault software, activity and registration, visualization, inventory, and ELN capabilities all address today’s markets. Secure, web-based collaborative technologies are especially applicable to the informatics needs of (and broadly used by) public-private-partnerships (PPPs). Web-based platforms are a natural fit for collaboration due to the economic, architectural, and design benefits of a single platform that transcends any one organization’s solo requirements. In contrast to the CDD vault for today’s collaborations, CDD’s Research Informatics Group invents bleeding edge technologies for tomorrow’s needs. For example, open source descriptors and model sharing capabilities allow for platform-independent collaborations, even for sensitive data and IP, with groups reticent to share. CDD and Pfizer have demonstrated that these open source descriptors and models were statistically like commercial models. The main idea is to democratize model building to engage experimentalists to want to use models. As a second example, the recently developed BioAssay Express (BAE) technology streamlines the conversion of human-readable assay descriptions to computer-readable information Tanimoto (Jaccard) chemical and biological sequence similarity searches. BAE uses. Here the main idea is to allow researchers to easily search and combine similar bioassay protocols, even though those similarity searches are much more difficult than semantic standards to markup bioprotocols, which unleashes the full power of informatics technology on data that could previously only be organized by crude text searching (https://peerj.com/articles/cs-61/). These two newer web-technologies may be used not only with the CDD Vault, but also with other commercial, academic, or government built software tools. All open source components are in GitHub.

  • Development of somatostatin subtype 4 (sst4) agonists for potential use in Alzheimer’s disease

    Southern Illinois University Edwardsville
    USA
    Abstract

    Somatostatin (SST) occurs in two biologically active forms SST-14 and a N-terminally-extended form SST-28. SST exerts its effects by binding to a family of G protein-coupled receptors designated sst1-sst5. Structure-activity studies have shown that the tetrapeptide fragment, Phe7-Trp8-Lys9-Thr10, comprises the critical ?-turn of SST. Although Phe7 and Thr10 can be modified, Trp8 and Lys9 are essential for biological activity. Since nonpeptide SST ligands offer therapeutic advantages over peptides, a screening program was initiated to identify a nonpeptide SST ligand with affinity for sst1-sst5. The search focused on the following: An aromatic moiety to mimic Phe7; a heteroaromatic nucleus to mimic Trp8, and a primary amine or other basic group to mimic Lys9. Using these search criteria, NNC 26-9100 was identified as the first sst4 agonist having high affinity (Ki=6 nM) and 100-fold sst4/sst2 selectivity at cloned human sst4 receptors. In a forskolin-induced cAMP assay, NNC 26-9100 potently inhibited cAMP accumulation and was shown to be a full agonist. NNC 26-9100 increased the expression of the enzyme neprilysin in the SAMP8 mouse model of Alzheimer’s disease. Neprilysin is the major A?-42 peptide degrading enzyme in the brain. Our studies demonstrate that NNC 26-9100 reduces A?-42 peptide levels in mouse cortex and that this reduction is associated with increased expression of neprilysin. Acute and chronic administration of NNC 26-9100 also increased learning and memory in SAMP8 mice using the T-maze test. These results suggest that NNC 26-9100 is a disease-modifying agent with potential use in the treatment of Alzheimer’s disease. Current studies in our laboratory are focused on the discovery on novel heterocyclic scaffolds with high affinity and selectivity at sst4 receptors. Image

  • Nanoemulsion-Based Therapies: Antimicrobial, Anti-inflammatory and Drug Delivery Properties

    NanoBio Corporation
    USA
    Abstract

    Nanoemulsions (NE) are oil-in-water emulsions containing high energy nanometer-sized droplets stabilized by surfactants, and specifically designed for topical and mucosal targeted delivery. Due to their size (less than 500nm) and surface-active properties they to traverse the skin via pores, hair follicles, and mucosal membranes, but are excluded from entering the tight junctions of the epithelium. As a result, they can be highly bioavailable in the tissues, without causing disruption of the normal epithelial matrix. Nanoemulsions can delivery agents across the nasal mucosa for the desired clinical (therapeutic) effect. We have testing these formulation in high-throughput screens and found NE induced immunogenicity and antigen delivery are facilitated through initial contact interactions between the NE droplet and mucosal surfaces, which promote prolonged residence of the vaccine at the site of application, and thus cellular uptake. We have incorporated small molecule, peptides/proteins and large macromolecules in optimized nanoemulsion formulation for transmucosal delivery. Nanoemulsions can delivery agents across the nasal mucosa for therapeutic effects. Nanoemulsions delivered topically are inherently antimicrobial and lyse pathogens upon contact, thereby overcoming existing resistance mechanisms. Other anti-microbial, anti-fungal and anti-viral agents can be entrapped inside the nanoemulsion and enhanced drug delivery of these agents. Studies of a novel nanoemulsion formulated with other agents demonstrates significantly higher levels are achieved as compared to commercially available products. Recently discovered, a topical nanoemulsion therapy acting as a topical antimicrobial was found to halt burn wound progression in a swine burn wound model. The nanoemulsion reduced the bacterial growth in the burn wound to minimal levels compared to saline and silver sulfadiazine and significantly reduced levels of dermainflammatory cytokines. By reducing excess influx of neutrophils into the burn wound and modulating the pro-inflammatory response, the nanoemulsion formulations attenuated burn wound progression in the early post-injury phase and prevented conversion of burn wounds from partial thickness to full thickness. This discovery, if demonstrated in man, would lessen the need for skin grafting, speed recovery, result in fewer infectious complications, and improve the outcomes by preventing the conversion to full thickness wounds. Among its many uses nano emulsion therapy is a potential new breakthrough treatment for preventing burn wound progression.

Drug Discovery and Development | Computer Aided Drug Design (CADD) | Medicinal Chemistry in Modern Drug Discovery | Drug Metabolism and Drug Designing
Chair
Speaker
  • A non-conventional therapeutic approach to epilepsy in children
    Speaker
    Mariana Babayeva
    Touro College of Pharmacy
    USA
    Biography

    Mariana Babayeva MD, PhD is an Associate Professor at Touro College of Pharmacy, New York, NY. In addition to her role at Touro, Dr. Babayeva is also an Adjunct Professor at Rockefeller University and Visiting Scientist at Arnold and Marie Schwartz School of Pharmacy of LIU. Dr. Babayeva has over 14 years of experience in clinical practice. She is recognized for her expertise in the pharmacokinetics and the use of animal and organ models. Dr. Babayeva has conducted several international research projects. Dr. Babayeva has been published in peer-reviewed journals and serving as an editorial board member of repute.

    Abstract

    Children epilepsy is a complex disease with a variety of distinct syndromes. Treatment of pediatric epilepsy is challenging. Childhood epilepsies are commonly associated with seizures that are resistant to existing treatment methods. Therefore, treatment of pediatric epilepsy requires more effective therapy to avoid short-term and long-term neurological disorders. Marijuana has been used to treat disease since ancient times. Marijuana ingredients Cannabidiol (CBD) and D9-Tetrahydrocannabinol (THC) have created a significant research interest as potential therapy options in epilepsy treatment. THC is the major psychoactive component of marijuana that aids in reducing epileptic seizures. CBD has proven to have anticonvulsant effect not only in experimental models but also in clinical studies. Research studies have provided strong evidence for safety and anticonvulsant properties of medical marijuana. Principal concerns regarding the use of medical marijuana in children include lack of standardization and regulation, imprecise dosing, possible adverse side effects and medication interactions. Speaker Biography Mariana Babayeva is an Associate Professor at Touro College of Pharmacy, New York. In addition to her role at Touro, she is also an Adjunct Professor at Rockefeller University and Visiting Scientist at Arnold and Marie Schwartz School of Pharmacy of LIU. She has over 14 years of experience in clinical practice. She is recognized for her expertise in the pharmacokinetics and the use of animal and organ models. She has conducted several international research projects. She has been published in peer-reviewed journals and serving as an Editorial Board Member of repute.

  • Small molecule pro-neurotrophic therapeutic activity in murine models of Alzheimer’s disease
    Speaker
    Stuart Maudsley
    Universiteit Antwerpen
    Belgium
    Biography

    Stuart Maudsley has been recognized as a visionary pioneer in science (both physical and biomedical) from childhood where his work was publicized on the national television program ‘The Power Game’ – a U.K. wide engineering Olympiad. Stuart has been subsequently awarded and recognized throughout his career as both an intellectual innovator and as an excellent scientist. Stuart’s primary contribution to science is in the field of receptor systems biology and pharmacotherapeutics design – within this field Stuart is one of the world’s leading young Investigators. Stuart graduated from the University of Leeds with First Class Honors in Pharmacology and was awarded the Pfizer Prize for undergraduate research. For his doctoral work Stuart was one of only 6 recipients (from a University population of 40,000) of the Universities venerated ‘Named Scholarships’, i.e. the Ackroyd, Brotherton and Brown Scholarship. After gaining his Ph.D. in Receptor Pharmacology, he was then awarded a Howard Hughes Medical Institute Fellowship Award to train with Professor Robert Lefkowitz (2012 Nobel Laureate in Chemistry) at Duke University. Following this fellowship Stuart was instantly recruited to be Principal Investigator of the Receptor Biology Section at the Medical Research Council (MRC) -Human Reproductive Sciences Unit at the University of Edinburgh. During his time at the MRC his drug discovery and development abilities was implicit in his recruitment as a scientific advisor to Ardana Bioscience Inc. where he subsequently developed a novel prostate cancer therapeutic. To broaden his already considerable biomedical experience Stuart then accepted the position of Head of the Receptor Pharmacology Unit at the National Institutes of Health (NIH-National Institute on Aging) at the Johns Hopkins University Medical Center.

    Abstract

    Age-related neurodegenerative diseases, such as Alzheimer’s disease, will represent one of the largest future burdens on worldwide healthcare systems due to the increasing proportion of elderly in our society. As deficiencies in neurotrophins are implicated in the pathogenesis of many age-related neurodegenerative disorders, it is reasonable to consider that global neurotrophin resistance may also become a major healthcare threat. Central nervous system networks are effectively maintained through aging by neuroprotective and neuroplasticity signaling mechanisms which are predominantly controlled by neurotrophin receptor signaling. Neurotrophin receptors are single pass receptor tyrosine kinases that form dimeric structures upon ligand binding to initiate cellular signaling events that control many protective and plasticityrelated pathways. Declining functionality of the neurotrophin ligand–receptor system is considered one of the hallmarks of neuropathological aging. Therefore, it is imperative to develop effective therapeutic strategies to contend with this significant issue. The development of nonpeptidergic, small-molecule ligands can overcome these limitations, and productively regulate this important receptor system with beneficial effects. We have found that in multiple models of Alzheimer’s disease the previously employed anti-depressant Elavil can exert potent pro-neurotrophic activity through a series of complementary mechanisms. This small molecular agent possesses the capacity to significantly enhance cognitive performance in mouse models possessing considerable levels of dementia and amyloid pathology. In this respect agents such as Elavil may represent an important addition to a new wave of therapeutic strategies against dementia.

  • Strategies for pathology-activated generation of reelin trafficking modulators for altering late-onset Alzheimer’s disease progression
    Speaker
    Ronald A. Hill
    University of Louisiana Monroe
    USA
    Biography

    Ronald A. Hill, B.S.Chem., Ph.D., is a native of central Ohio. He graduated from the University of Michigan in 1982 with a B.S.Chem. degree, completing an honors thesis project in mechanistic organic chemistry with Professor Peter A. S. Smith. He then spent 4-1/2 years engaged in analytical chemistry and biopharmaceutics R&D at the Upjohn Company in Kalamazoo, MI, followed by graduate study at The Ohio State University, where he completed a Ph.D. in Pharmacy, with emphases in synthetic medicinal and computational chemistry. His graduate research was directed by Professors Duane D. Miller and Jan K. Labanowski (Ohio Supercomputer Ctr.). In 1991, he established a research group at ULM, mainly engaged in areas of synthetic medicinal and bioanalytical chemistry. Historically, his research, funded at various times by the NIH and the AHA, focused mostly on projects related to the central nervous system, particularly the efficient delivery of small organic molecules to the CNS and their distribution, biotransformation, and actions therein. Over the years, he also collaborated extensively with investigators working in areas of pharmaceutics, toxicology, pharmacology, and clinical sciences, and also gained extensive acumen in molecular therapeutics design, molecular biopharmaceutics, and molecular toxicology. His more-recent educational duties at the Ph.D. and Pharm.D. levels, and ongoing research collaborations in areas including cancer and Alzheimer’s disease, has demanded even more breadth and depth of knowledge, especially in areas bridging early discovery science to clinical application. He also currently serves as a member of the Expert Panel for the Cosmetic Ingredient Review, a key safety assessment body for non-drug personal care products. He has served as major adviser for a number of M.S. and Ph.D. students, and on the graduate committees of now more than 60 others, all of whom have an admirable record of accomplishment in industry, government, or academia.

    Abstract

    Compelling evidence continues to accrue that late-onset (non-familial) Alzheimer’s disease (LOAD), arising early in olfactory structures of the brain, progresses in a spatiotemporally consistent pattern via propogating “inflammaging” processes; predisposing susceptibility may be established as early as gestationally. Genome-wide association studies (GWASs) of cognitively uncompromised individuals who exhibit apparent high pathology suggest that select combinations of genetic attributes can confer resistance to cognitive decline; and, although certain specifics of pathological signatures differ from those in cognitively deteriorating individuals, these might reflect successful defense against an otherwise pathological chain of events. A central player emerging from these GWASs is reelin, a large glycoprotein component of the extracellular matrix (ECM). Though historically regarded mostly as a key player in embryo-fetal development reelin exhibits functional interplay in the adult brain with other molecular constituents having clearly established associations with LOAD, such as apolipoprotein E, and with the responsiveness states of inflammaging-associated cells, notably microglia. The complexities and relative paucity of knowledge regarding ECM maintenance, remodeling, and functional dynamics, and the analytical challenges involved in achieving increased clarity, means that gaining therapeutically actionable traction will be difficult; however, the tantalizing thought that GWASs of these individuals may be showing us ways forward motivates rising to these challenges. Reelin possesses multiple functional domains, and certain reelin fragments exhibit trafficking and function disparate from intact glycoprotein. Very recently, ADAMTS-3 was identified as the catalyst of a proteolytic cleavage of reelin shown to be inactivating in terms of reelin’s canonical activities. Because of reelin remains heavily involved during adulthood in dynamic brain maintenance and remodeling, deleterious consequences can be expected from anatomically untargeted alterations in reelin function. Potential strategies for pathologyactivated, localized generation of suitable modulators will thus be needed, and progress with respect to devising such strategies will be shared in this presentation. Speaker Biography Ronald A Hill is now spanning almost 35 years, over a pharmaceutical sciences career. He has aimed to become a generalist with high-level acumen in relating the Chemistry of biologically active molecules to their interactions with, and actions on, humans and their hosted organisms (normal microbiome, microbial pathogens, parasites). The central focus of his own research has always related to the CNS, guided also by the aim of constantly gaining acumen in molecular therapeutics design, molecular biopharmaceutics, and molecular toxicology and in general, the science of successfully bridging discovery at its earliest stages to clinical application. His educating duties at the PhD and PharmD levels are extensive, and carried out with the underlying hope that the molecular science and molecular design will be intelligently and artfully acted on in clinical practice. His current research collaborations center on neurodegenerative conditions and cancer.

  • Effect of manufacturing process and container closure configurations on critical quality attributes of generic parenteral drug product
    Speaker
    Lakshmi Prasanna Kolluru
    Medefil Inc.,
    USA
    Biography

    Lakshmi Prasanna Kolluru is currently working as Sr. Formulation Scientist at Medefil, Inc, a generic pharmaceutical company. She is responsible for leading product development project teams all the way from kick-off to product approval. Prior to joining Medefil, she has served in formulation, analytical and clinical development groups across brand pharma, generic pharma and contract research organizations. She has graduated with a PhD in Pharmaceutical Sciences from Mercer University, Atlanta, GA. Her thesis research focusing on development of novel targeted drug delivery system for tumor theragnosis has been recognized internationally by American Association of Pharmaceutical Scientists (AAPS) for excellence in graduate research. In addition to her active research, she serves as Editorial Board Member and Peer-Reviewer for several international journals.

    Abstract

    Purpose/Introduction: Product development of generic parenteral products involves extensive studies to optimize formulation process and manufacturing conditions such that the developed product is like Reference Listed Drug (RLD) in terms of all Critical Quality Attributes (CQA) over stability. CQA’s are properties of drug product which have significant effect on product quality. Typical CQA’s for a drug product include pH of the formulation, assay of the chemical of interest, impurities, visual appearance, particulate matter, color and clarity of the solution. In this present work, we present two case studies of generic parenteral product development to optimize pH of the drug products under study. Methods: pH of a formulation is a critical quality attribute as it significantly affects solubility and stability of the drug product. In addition, pH of a parenteral drug product has significant clinical effects such as electrolyte imbalances. In first case study, we evaluated effect of container closure configurations on pH of the drug product. We formulated the drug product and filled it in various treated and non-treated glass vials, stoppered, sealed and placed on stability as per International Conference on Harmonization (ICH) guidelines. In the second case study, we evaluated effect of nitrogen sparging during compounding on pH of the drug product. We prepared three batches of drug product. First batch was prepared under ambient atmospheric conditions without nitrogen sparging, another by sparging the water for 30 minutes before addition of Active Pharmaceutical Ingredient (API) and blanketing the formulation with nitrogen for rest of compounding process; and third batch with continuous nitrogen sparging throughout compounding. pH of all the three batches are monitored at pre-determined time intervals throughout the manufacturing process. Results: Stability data of the drug product in case study 1 monitored over 6 months at 25C/65% RH and 40C/75% RH suggest that the formulation in untreated vials showed drastic change in pH, with the data at 3M and 6M even failing to meet pH specifications for the finished product. However, formulation filled in treated vials has well controlled pH and within specifications at all conditions up to 6M on stability. Data analysis of various batches from case study 2 suggests better control of pH in the second batch with sparging the water for 30 minutes before addition of nitrogen and blanketing throughout the compounding process. Conclusion: Both the case studies suggest that appropriate container closures and optimal manufacturing process have significant effect on pH of parenteral drug products and should be closely evaluated during product development.

  • Effect of manufacturing process and container closure configurations on critical quality attributes of generic parenteral drug product: A case study of pH
    Speaker
    kissi Mudiey Yesu
    Ethiopian Public Health Institute
    Ethiopia
    Abstract

    Background: The safe use of medicines is a critical issue for all health care professionals. Cancer refers to a group of diseases that are associated with a disturbance in the control of cell growth and metabolism. Indeed, the unbalanced control of cellular proliferation is a primary characteristic of cancer cells and, as such, any molecule capable of inhibiting cancer cell proliferation may also be useful as a potential chemo-preventive agent. Throughout history, antioxidants have been the most significant source of anticancer and chemopreventing agents. More than 1,000 different phytochemicals are already proved to possess interesting chemopreventing activities. Antioxidants consist of a wide variety of biologically active phytochemicals including phenolics, flavonoids, carotenoids, etc. that have been shown to suppress early and late stages of carcinogenesis. Objective: The objective of this study was to review recent biochemical and molecular mechanisms, in relation to natural and synthetic chemopreventing substances (antioxidants) for cancer control and management. Findings: Antioxidants exert anticancer effects via a variety of mechanisms, including removal of carcinogenic agents, modulation of cancer cell signaling and cell cycle progression, promotion of apoptosis and modulation of enzymatic activities. Conclusion: This review provides an updated and comprehensive overview on the anticancer effects of antioxidants in-vitro and in-vivo animal models including recent intervention studies. Finally, possible mechanisms of action involving antioxidant and pro-oxidant activity as well as interference with cellular functions are discussed. Speaker Biography Kissi Mudie has completed his MSc in Medical Biochemistry from Addis Ababa University, School of Medicine. He is the Director of National clinical chemistry laboratory, Ethiopian Public Health Institute. He has published more than 16 papers in reputed journals and has been serving as Researcher.

  • Nanostructured Lipid Carriers (NLC)-Based gel for the topical delivery of azelaic acid: Designing, characterization and in-vitro evaluation
    Speaker
    Deepinder Singh Malik
    Punjab university
    India
    Biography

    Deepinder Singh Malik is an Ph.d student in Punjab University

    Abstract

    Azelaic acid (AZA) is a naturally occurring dicarboxylic acid, reported to be effective in management of mild to moderate acne vulgaris. However, few noticeable dose-related side effects limit its therapeutic applicability. Therefore, the study was directed towards the optimization, formulation and evaluation of the AZA loaded nano-structured lipid carrier (NLCs) to enhance its payloads and achieve sustained release at the target site. NLCs were prepared by melt emulsification and ultra-sonication method employing glyceryl monostearate and oleic acid as solid and liquid lipid, respectively. The formulation was optimized employing design expert software taking sonication time, amplitude and drug concentration as independent variables with particle size and drug entrapment as dependent variables. The optimized preparation so formed was incorporated into aloe-vera based carbopol gel and evaluated for its size, morphology, pharmacokinetic and pharmacodynamic parameters. NLCs were found to possess mean particle size in a range of 45-48 nm with low polydispersity index value (~ 0.4) and encapsulation efficiency of ca. 82%. It was further verified employing transmission electron microscopy which depicted the formation of uniform surfaced spherical nanoparticles. In-vitro permeation and skin retention studies revealed significant retention of AZA within the skin with minimum penetration across the skin. Draize patch test exhibited no signs of irritation/lesion on the skin indicating its non-irritating nature. Skin distribution analysis employing rhodamine 6G as a fluorescent dye unveiled the deposition of NLCs preparation to the deeper layers of skin. Thus, as per experimental findings, NLCs may be explored as promising carriers for site specific targeting.

Day 2

KEYNOTE SPEAKERS
  • Innovative Patient-Centric Service Model Helps Speed Patient Recruitment and Increase Retention in Virtual and Traditional Study Designs

    GlobalCare Clinical Trails
    USA
    Abstract

    Patient recruitment and retention are key factors, and generally the most challenging, in meeting the objectives and success of clinical trials. Clinical trial costs, complexity and development timelines have continued to increase over the past several years as well as the burden to participating patients and caregivers. We are approaching a critical juncture where traditional trial designs can no longer be justified or sustained. More patient-centric trial models and novel trial designs incorporating mobile technologies are available to make studies more patient-friendly as well as more cost efficient. A patient-centric service model has evolved over the past two decades allowing study visits to be conducted at the patient’s home where it is more convenient and comfortable than at the investigator site. By conducting selected protocol visits at home, the workplace or other alternate location, ambulant healthcare providers offer a way for patients to participate in trials regardless of typical barriers of study duration, visit frequency, disease state, distance to site, site office hours, or family, school or work obligations. By making trials more convenient for patients, this service model has demonstrated that more patients are willing and able to participate and remain in studies. Virtual study (central-site) designs have been introduced to also address real world challenges to gain access to hard to reach patients residing in rural areas and those who may have mobility issues and to utilize available technologies to remotely consent and monitor patients. There still remains the need for local clinical support to obtain safety labs or train patients on utilizing the mobile devices. The use of ambulant healthcare providers to conduct at-home study visits can result in significantly more cost-effective, efficient and patient-friendly clinical trial programs conducted globally than traditional studies. This session will: • Explore the use of an innovative, patient-centric approach to conducting selected study visits via an ambulant healthcare network to reduce patient burden and other barriers to study participation • Show how conducting selected protocol visits at the patient’s home or alternate location rather than at the investigator site can make study participation more convenient and comfortable for patients resulting in faster recruitment and better compliance and retention • Present case studies using ambulant care services • Demonstrate win-win benefits for all stakeholders

  • Just right: Process from drug discovery to development

    kwong Eureka Solutions
    Canada
    Abstract

    The discovery and development of new drugs is a very complex machine. Despite increasing investments and process improvements in research and development, the survival rates of drugs in late phases of development has languished during the past decade. Recent analysis of such decline in late phase drug development was attributed to non-drug like compounds synthesized by Medicinal Chemists which exhibit low aqueous solubility with highly potent ligands which will bind to a target. With the current challenges facing “big Pharma”, small biotech start-up (BSU’s) with limited internal research and development resources in addition to true virtual pharmaceutical companies (VPC’s) with only an experienced team of managers without any R&D capabilities are quickly emerging which adds another layer of complexity in arriving to a “just right” approach from drug discovery to development. To recover from such failed approaches, a gate-keeper approach is now the norm, where preclinical and discovery collaborations result in a structure and property-based design. This design now used in lead optimization combines biological activity/potency focus with optimizing structural features of the candidate to optimize absorption and pharmacokinetics. This approach is then effectively progressed to the understanding and defining of solid state phase and formulation of the drug candidate when more material is available. Early engagement of the pharmaceutical development scientists on the identification of an optimal phase and formulation during drug discovery can add significant benefits in drug discovery efforts and downstream development. These benefits include the demonstration of dose limiting toxicity to establish acceptable and reproducible safety margins. Another benefit is the early identification of an optimal phase that minimize multiple changes in phase that can contribute to irreproducible plasma levels in various PK studies as candidate are being considered in toxicity studies. Furthermore, formulation development in preclinical studies will also provide some risk mitigation in the development of clinical trial materials. The current presentation will focus on the “must do” list to successfully help progress drug discovery candidates from any pharma organization to development with low risk that provide a balance of speed and quality.

Pharmaceutical Research & Development| Clinical Trials & Regulatory Affairs | Drug Discovery in Preclinical Research | Novel Therapeutics in Drug Designing | Nanotechnology in Drug Discovery
Chair
Speaker
  • The study on the effect of non-enzymatic glycation on the interaction of human serum albumin and sodium-fluorescein, via spectroscopic analyses
    Speaker
    Priyankar sen
    VIT University
    India
    Abstract

    The binding of SF to Human Serum Albumin (HSA) has been predicted by molecular docking and investigated by circular dichroism (CD) and fluorescence spectroscopy with or without glycation at temperatures 296K, 301K, and 310K. The binding parameters were calculated by quenching of emission spectrum of a constant concentration of SF (2 ?M) at 513 nm against increasing concentrations of glycated or unmodified HSA as quencher starting from stochiometry ratio of 1:1. Sodium Fluorescein (SF) is a fluorescent tracer dye used extensively in diagnostic tools in the field of Ophthalmology, particularly in intravenous fluorescein angiography (IVFA). The HSA-SF interaction found to be a static binding. The Stern- Volmer constants (Ksv) were in the range of ~104 M-1 and other thermodynamic parameters like enthalpy (?H0), free energy (?G0) and entropy (?S0) are like albumin ligand bindings reported by previous workers. The interactions were found to be spontaneous, irrespective of temperature or glycation. Glycated HSA is clinically used to monitor unstable glycemic controls in diabetic patients. 39% increase in binding affinity (log K) and free energy (?G0) is reported on glycation at 310 K (room temperature), which may be important in the SF based angiographies. Further, on glycation HSA-SF binding seems to change from an enthalpy-driven to an entropy-driven reaction. SF shows best binding to FA binding site III of HSA, which also overlaps with drug binding site II of sub domain IIIA. Leu-430 seems to play a pivotal role in the interaction. This is the first report of glycated HSA and SF binding and comparison between the thermodynamic parameters of the bindings in the absence and presence of glycation at different temperatures. Speaker Biography Priyankar Sen is working in the field of protein folding and protein ligand interactions for the enhanced understanding of the molecular behavior of proteins, specifically albumins. He has done his PhD from Rizwan Khan’s Lab in IBU, Aligarh Muslim University, India and Post-doctorate from Salunke’s Lab, NII, New Delhi. Out of 5 years’ Doctoral and 8 years Post-doctoral research, he has published 21 papers in international peer reviewed journals. He is currently working as Assistant Professor in VIT University. Currently, he is focusing on expression and modification of therapeutically important proteins and further scale up in bioreactors.

  • Novel synthetic inhibitors of eosinophils with potential anti-asthmatic activity
    Speaker
    Tarek Aboul-Fadl
    Assiut University
    Egypt
    Abstract

    Asthma is a major public health issue with high and increasing prevalence rates and a concomitant increase in morbidity and mortality. Asthma is estimated to affect 300 million people, with an expected increase to 400 million worldwide by 2025. Many factors may have contributed to the rise of the problem of bronchial asthma. Increasing air pollution, fast modernization, and widespread construction work are some of the reasons for asthma to thrive. The situation is complicated by poor access to medical services and high price of effective drugs.Asthma is a chronic inflammatory condition, triggered by environmental factors in genetically predisposed individuals, and is characterized by mast cell, T lymphocyte, and eosinophil infiltrates in the bronchial mucosa. Eosinophils are recruited to sites of specific inflammatory reactions, especially during allergic diseases and are correlated with asthma severity. In spite of their numerous adverse effects inhaled glucocortocoids have been established as the standard treatment for asthma. Therefore, an urgent need exists for alternative treatments to overcome these undesirable side effects of steroid therapy and to provide another effective agent for the treatment of asthma. Lidocaine was reported to inhibit interleukin-5 (IL-5)- mediated survival and activation of human eosinophils. It can replace inhaled glucocorticoids for the treatment of asthma; however, lidocaine has many undesired side effects mainly due to its sodium channel activity including anesthesia. Accordingly, the current work aims to modify lidocaine structure to obtain analogs with minimum sodium channel and enhanced IL-5 inhibitory activity. The hypothesis supported by ligand-based pharmacophore modeling generated using different molecular modeling programs. Speaker Biography Tarek Aboul-Fadl is a Prof. of Medicinal Chemistry at Faculty of Pharmacy, Assiut University/Egypt. Dr Aboul-Fadl received his PhD in Pharmaceutical Medicinal Chemistry from Assiut University (1994) under the channel system and joint supervision scheme between Assiut University and Josai University/Japan. Dr Aboul- Fadl performed his postdoctoral training as a postdoctoral research fellow and Scientist at Institute of Pharmaceutical Chemistry, University of Vienna, Austria (1997- 1998), Institute of Pharmacy and Food Chemistry, University of Erlangen-Nürnberg, Germany (1999 and 2013) and Department of Medicinal Chemistry, University of Utah, USA (2001-2002 and 2004-2005). Dr Aboul-Fadl joined Department of Medicinal Chemistry as an assistant Prof. in 1994, then promoted to associate Prof. in 1999 and to Professor in 2004. Dr Aboul-Fadl is a member of Egyptian Syndicate of Pharmacists since 1984, Egyptian Society of Pharmacists since 1994, American Chemical Society since 2002 and The Stop TB Partnership Working Group on New TB Drugs (WGND) since Feb. 2010

  • In silico and in vivo assays of a borinic DOPA-derivative for Parkinson disease
    Speaker
    Marvin A Soriano-Ursúa
    Instituto Politécnico Nacional
    Mexico
    Biography

    Marvin A Soriano-Ursúa has completed his PhD from Escuela Superior de Medicina del Instituto Politénico Nacional, México. He is a Member of the National System of Researchers, and he is Head of the Physiology Laboratory. He has focused on the rational drug design having boron-containing compounds as main moiety, as well as, the different effects of these compounds on human physiology, particularly on G-Protein coupled receptors. He has authored more than 35 publications that have been cited over 200 times, and he has been serving as an Editorial Board Member and Reviewer of repute scientific journals.

    Abstract

    The boron atom has some chemical properties which confer it advantages to be added in potential new drugs. One of these advantages has been inferred by in silico assays interaction on receptors or proteins with serine, threonine or tyrosine on the active site. In this sense, catecholamine receptors (belonging to the G-protein coupled receptors family) have a conserved binding site with three serine-residues involved in receptor activation. In this work, we tested the potential activity of 3-D models representing adducts of levodopa or dopamine on models of catecholamine human receptors (emphasis on betaadrenoceptors and D2 and D3 receptors) by in silico docking analyses. Then, we synthesized and characterized a compound with potential activity on D2 receptor judged with the affinity score and binding mode on this receptor. Interestingly, the boron-containing compound contacts on the orthosteric site with higher affinity than Levodopa or dopamine, but its boron atom is not directed to serine residues in fifth transmembrane domain. This compound is an adduct of levodopa and an aryldiphenylborinic acid, which was tested in a C57/BL6-mice model of parkinsonism induced by peritoneal administration of MPTP (a well-known toxin on catecholaminergic system). The compound induced improved performance of administered mice on motor tests but several pharmacological tests are required to elucidate the putative mechanism of action. Speaker Biography Marvin A Soriano-Ursúa has completed his PhD from Escuela Superior de Medicina del Instituto Politénico Nacional, México. He is a Member of the National System of Researchers, and he is Head of the Physiology Laboratory. He has focused on the rational drug design having boron-containing compounds as main moiety, as well as, the different effects of these compounds on human physiology, particularly on G-Protein coupled receptors. He has authored more than 35 publications that have been cited over 200 times, and he has been serving as an Editorial Board Member and Reviewer of repute scientific journals.

  • Modified glycol chitosan nanocarriers carry hydrophobic materials into tumours
    Speaker
    Akthar Aman
    Shaheed Benazir Bhutto University
    Pakistan
    Biography

    Akhtar Aman has completed his PhD from Peshawar University under Hec Scholarship. During his PhD studies, he also worked as Visiting Scientist at Center for Cancer Medicine, School of Pharmacy, University College London, UK. He is currently serving as Assistant Professor of Pharmaceutics at Shaheed Benazir Bhutto University, Sheringal, Pakistan. He has published more than 10 papers in reputed journals

    Abstract

    Development of efficient delivery system for hydrophobic drugs remains a major concern in chemotherapy. The objective of the current study is to develop polymeric drugdelivery system for etoposide from amphiphilic derivatives of glycol chitosan, capable to improve the pharmacokinetics and to reduce the adverse effects of etoposide due to various organic solvents used in commercial formulations for solubilization of etoposide. As a promising carrier, amphiphilic derivatives of glycol chitosan were synthesized by chemical grafting of palmitic acid N-hydroxysuccinimide and quaternization to glycol chitosan backbone. To this end, a 7.9 kDa glycol chitosan was modified by palmitoylation and quaternisation into 13 kDa. Nano sized micelles prepared from this amphiphilic polymerhad the capability to encapsulate up to 3 mg/ml etoposide. The pharmacokinetic results indicated that GCPQ based etoposide formulation transformed the biodistribution pattern. AUC 0.5- 24 hr showed statistically significant difference in ETP-GCPQ vs. commercial preparation in liver (25 vs 70, p<0.001), spleen (27 vs. 36, P<0.05), lungs (42 vs. 136, p<0.001), kidneys (25 vs. 30, p<0.05) and brain (19 vs. 9, p<0.001). Using the hydrophobic fluorescent dyeNile red, we showed that micelles efficiently delivered their payload to MCF7 and A2780 cancer cells invitro and to A431 xenografttumor in-vivo, suggesting these systems could deliver hydrophobic anti-cancer drugs such as etoposide to tumors. The pharmacokinetic results indicated that the GCPQ micelles transformed the biodistribution pattern and increased etoposide concentration in the brain significantly compared to free drug after intravenous administration. GCPQ based formulations not only reducedside effects associated with current available formulations but also increased their transport through the biological barriers, thus making it a good delivery system.

  • Rational design of guanylthiourea derivatives as antimalarial agents
    Speaker
    Shweta Bhagat
    National Institute of Pharmaceutical Education and Research
    India
    Abstract

    Plasmodium falciparum dihydrofolate reductase (PfDHFR) enzyme is one of the validated targets for antimalarial drug discovery. The quadruple mutant of PfDHFR is resistant to the known anti-PfDHFR drugs (e.g. proguanil, pyrimethamine and trimethoprim). Recently, P218 was identified as a potential lead molecule. In this work, a rational drug design strategy was adopted to identify guanylthiourea (GTU) derivatives as a potential PfDHFR inhibitor. Electronic structure analysis of the GTU moiety was carried out to determine the correct tautomeric form which was 11.99 kcal/mol more stable than the previously reported structure in the literature. Once acceptable structure was established; in silico investigations on the wild type/quadruple mutant PfDHFR and various ligands (including MESP analysis, molecular docking studies) were performed to design novel GTU derivatives as potential PfDHFR inhibitors. Three series of GTU derivatives were synthesised, by reacting bromides with GTU under reflux and microwave condition. The synthesized compounds were first evaluated for in vitro PfDHFR inhibitory activity, resulting in the identification of two compounds (100 ?M and 0.4 ?M). Further, in vivo studies recognized six compounds with high mean survival time, out of which one compound was identified to be curative. This work reports a systematic rational approach for the structure-based design of potential antimalarial agents.

  • Chemical composition, antioxidant and antibacterial activity of Thuja orientalis essential oil
    Speaker
    Wajaht A Shah
    Punjab university
    India
    Biography

    Essential oils derived from many aromatic plants are well known to possess cytotoxic, antioxidant, antifungal, insecticidal and antimicrobial activities. This work was carried out to evaluate chemical composition, antioxidant and antibacterial activity of Thuja orientalis essential oil. Thuja orientalis (family: Cupressaceae) is widely cultivated as a common ornamental plant. It possesses anti-plasmodial, antioxidant and elastase inhibitory activities. Chemical composition and pharmacological potential of hydro distillate from Thuja orientalis are reported in this study. Fresh fruits were subjected to conventional hydrodistillation. Antioxidant activity was assessed as free radical scavenging capacity (RSC) towards 2, 2-diphenyl-1-picrylhydrazil (DPPH) radicals and antibacterial activity was evaluated against six test bacteria by agar well diffusion method. Qualitative and quantitative analysis of Thuja orientalis hydrodistillate by gas chromatography coupled with mass spectrometry revealed the presence of nineteen constituents, representing 94.6% of the total oil. The major constituents of oil were alpha-pinene (83%), sabinene (2.6%), delta-3-carene (2.5%). The oil showed appreciable antibacterial effect against all Gram-positive and Gram-negative bacteria tested with MIC values between 12.8-25.6 ?g/ml. Therefore this oil could be used in the formulation of antimicrobial and antioxidant agents.

    Abstract

    Essential oils derived from many aromatic plants are well known to possess cytotoxic, antioxidant, antifungal, insecticidal and antimicrobial activities. This work was carried out to evaluate chemical composition, antioxidant and antibacterial activity of Thuja orientalis essential oil. Thuja orientalis (family: Cupressaceae) is widely cultivated as a common ornamental plant. It possesses anti-plasmodial, antioxidant and elastase inhibitory activities. Chemical composition and pharmacological potential of hydro distillate from Thuja orientalis are reported in this study. Fresh fruits were subjected to conventional hydrodistillation. Antioxidant activity was assessed as free radical scavenging capacity (RSC) towards 2, 2-diphenyl-1-picrylhydrazil (DPPH) radicals and antibacterial activity was evaluated against six test bacteria by agar well diffusion method. Qualitative and quantitative analysis of Thuja orientalis hydrodistillate by gas chromatography coupled with mass spectrometry revealed the presence of nineteen constituents, representing 94.6% of the total oil. The major constituents of oil were alpha-pinene (83%), sabinene (2.6%), delta-3-carene (2.5%). The oil showed appreciable antibacterial effect against all Gram-positive and Gram-negative bacteria tested with MIC values between 12.8-25.6 ?g/ml. Therefore this oil could be used in the formulation of antimicrobial and antioxidant agents.

Mail us at

For General Queries
drugdiscovery@alliedconferences.org
For Regsirtation Queries
drugdiscovery@alliedmeetings.com
For Exhibitior Queries
drugdiscovery@alliedconferences.org
More details about sponsorship:sponsors@alliedacademies.com

Terms and Conditions

Responsibility

Delegates are personally responsible for their belongings at the venue. The Organizers will not be held responsible for any stolen or missing items belonging to Delegates, Speakers or Attendees; due to any reason whatsoever.

Insurance

Registration fees do not include insurance of any kind.

Transportation

Please note that any (or) all transportation and parking is the responsibility of the registrant.

Press/Media

Press permission must be obtained from Allied Academies Conferences Organizing Committee prior to the event. The press will not quote speakers or delegates unless they have obtained their approval in writing. The Allied Academies is an objective third-party nonprofit organization. This conference is not associated with any commercial meeting company.

Requesting an Invitation Letter

For security purposes, letter of invitation will be sent only to those individuals who had registered for the conference. Once your registration is complete, please contact drugdiscovery@alliedconferences.org to request a personalized letter of invitation.

Regarding refunds, all bank charges will be for the registrants account.

This cancellation policy was last updated on December 12, 2016.

Cancellation, Postponement and Transfer of Registration

All cancellations or modifications of registration must be made in writing to drugdiscovery@alliedconferences.org

Cancellation Policy

If Allied Academies cancels this event for any reason, you will receive a credit for 100% of the registration fee paid. You may use this credit for another Allied Academies event which must occur within one year from the date of cancellation.

Postponement

If Allied Academies postpones an event for any reason and you are unable or unwilling to attend on rescheduled dates, you will receive a credit for 100% of the registration fee paid. You may use this credit for another Allied Academies event which must occur within one year from the date of postponement.

Transfer of registration

All fully paid registrations are transferable to other persons from the same organization, if registered person is unable to attend the event. Transfers must be made by the registered person in writing to drugdiscovery@alliedconferences.org . Details must be included the full name of replacement person, their title, contact phone number and email address. All other registration details will be assigned to the new person unless otherwise specified.

Registration can be transferred to one conference to another conference of Allied Academies if the person is unable to attend one of conferences.

However, Registration cannot be transferred if it is intimated within 14 days of respective conference.

The transferred registrations will not be eligible for Refund.

Visa Information

Keeping in view of increased security measures, we would like to request all the participants to apply for Visa as soon as possible.

Allied Academies will not directly contact embassies and consulates on behalf of visa applicants. All delegates or invitees should apply for Business Visa only.

Important note for failed visa applications: Visa issues cannot come under the consideration of cancellation policy of Allied Academies, including the inability to obtain a visa.

Refund Policy:

If the registrant is unable to attend, and is not in a position to transfer his/her participation to another person or event, then the following refund arrangements apply:

Keeping in view of advance payments towards Venue, Printing, Shipping, Hotels and other overheads, we had to keep Refund Policy is as following slabs-

  • Before 60 days of the conference: Eligible for Full Refund less $100 service Fee
  • Within 60-30 days of Conference: Eligible for 50% of payment Refund
  • Within 30 days of Conference: Not eligible for Refund
  • E-Poster Payments will not be refunded.

Accommodation Cancellation Policy:

Accommodation Providers (Hotels) have their own cancellation policies, and they generally apply when cancellations are made less than 30 days prior to arrival. Please contact us as soon as possible, if you wish to cancel or amend your accommodation. Allied Academies will advise the cancellation policy of your accommodation provider, prior to cancelling or amending your booking, to ensure you are fully aware of any non-refundable deposits.

 

Highlights from last year's Convention

Copyright © 2017-2018 Allied Academies, All Rights Reserved.