Scientific Program

Conference Series Ltd invites all the participants across the globe to attend 18th International Conference on Medicinal Chemistry & Targeted Drug Delivery Dallas, USA.

Day 1 :

Keynote Forum

Tatsuya Takagi

Osaka University, Japan

Keynote: SBDD of MDM2 inhibitors using FMO and data mining method

Time : 09:45- 10:25

Conference Series MedChem and TDD 2017, USA International Conference Keynote Speaker Tatsuya Takagi photo
Biography:

Tatsuya Takagi has completed his PhD from Osaka University. He had been an Assistant Professor of School of Pharmaceutical Sciences, Osaka University for 5 years. Then, since 1993, he had worked for the Genome Information Research Center, Osaka University as an Associate Professor until he became a Professor of Graduate School of Pharmaceutical Sciences, Osaka University in 1998. He has published more than 150 papers in reputed journals and had served as Chairman of Division of Structure-Activity Relationship of the Pharmaceutical Society of Japan for three years (until March 2017).
 

Abstract:

MDM2 (Mouse double minute 2 homolog) is known as a protein which is a significant negative regulator of p53. MDM2 is also considered to be E3 ubiquitin-protein ligase recognizing the N-terminal TAD (trans activation domain). Thus, MDM2-p53 interactions is proposed to be a promising therapeutic strategy for tumors. Previously, we reported a part of the FMO (Fragment Molecular Orbital) calculation results of MDM2 and its inhibitors at Chem-Bio Informatics Society (CBI). However, we could not obtain sufficient correlation between calculated and observed activities of the inhibitors. In this study, we added some FMO results and tried to obtain better correlation using data mining methods, such as PLS. First, we selected significant 53 amino acids from 85 ones for interactions between MDM2 and inhibitors considering the IFIE values. Then we obtained two latent variables as a result of PLS and cross validations. Resulted scatter plot between observed and calculated pIC50 of MDM2 is shown in Figure 1. we could obtain better correlation coefficient, R2=0.879. We are now calculating PIEDA of the complexes.
 

Conference Series MedChem and TDD 2017, USA International Conference Keynote Speaker Victor J. Hruby photo
Biography:

Victor J Hruby has received his PhD from Cornell University and has completed his Postdoctoral studies with Noble Laureate Vincent du Vigneaud. Currently, he is a Regents Professor at the University of Arizona, with major research interests in peptide hormones and neurotransmitters and their GPCR receptors, and their relationships to health and disease. He has over 1300 publications, chapters and reviews and over 25 patents. He has received numerous awards for his research, has been an editor and associate editor and on the Editorial Boards of several journals. He has served on several NIH Study Sections and been a consultant for many drug companies.
 

Abstract:

G-Protein Coupled Receptors (GPCRs) are targets for 30% of current drugs, but there are many unmet needs because these receptors and their ligands are intimately involved in many of our degenerative diseases. It has been difficult to obtain drugs that are effective and without side effects because there often are multiple subtypes of receptors and the endogenous hormones and neurotransmitters are non-selective. The 5 melanocortin receptors (MCRs) and the 3 opiate receptors (ORs) are important examples that are involved in many degenerative diseases, both central and peripheral. There is only 1 drug on the market for the MCRs, and the drugs on the market for the ORs are toxic and currently a great concern because of the drug overdose epidemic, which is costing billions and thousands of lives. To address this problem, we have developed a multimodal approach, using a combination of novel peptide and peptidomimetic scaffolds that address drug design in 3-dimensional space, with novel cyclic templates, computer assisted ligand/receptor interactions, orthosteric and allosteric agonist and antagonist activities, receptor selectivity and bioavailability for both the blood brain barrier and oral/transdermal availability. As time permits, we will illustrate this approach with design of melanotropin ligands that are highly selective agonists or antagonists for only 1 of the melanocortin receptors involved in pigmentary disorders, cancer, feeding and sexual disorders and neurodegeneration. For the opiate receptors, multivalent ligands that target opiate receptors and other receptors involved in pain pathways all in single ligands which do not have the toxicities of current opiates.

Keynote Forum

Jaein Ha

Korea University College of Medicine

Keynote: The Anticancer effect of a specific Myokine, Vimentin

Time : 10:50-11:30

Conference Series MedChem and TDD 2017, USA International Conference Keynote Speaker  Jaein Ha photo
Biography:

Jaein Ha is an Undergraduate student at Korea University College of Medicine. She has studied Organic Chemistry and is interested in the fields such as Bioorganic Chemistry and Pharmacology. Now, she is doing a research under her academic advisor, Kim, Hyeon Soo (Anatomy Department, Korea University College of Medicine). Her research interest is myokine, which is a molecule secreted from muscle cells. She tries to identify specific myokine which are associated with cell metabolism

Abstract:

Myokines are known to suppress some kinds of tumor. This fact makes it possible to explain the correlation between physical activities and cancer. The researcher suggests that Vimentin, an intermediate filament, is a novel myokine and has an anticancer effect on pancreatic cancer. Vimentin was shown to be secreted from muscle cells by muscle contraction. Furthermore, Vimentin treatment on L6 cell increased phosphorylation of AMPK and ACC. These results imply that Vimentin is associated with signaling pathways regulating various metabolisms. MTT assay results demonstrated that Vimentin controls the viability of pancreatic cancer cell, MIA-Pa-Ca-2. The study provides considerable insight into role of Vimentin as a myokine. Muscle contraction leads to secretion and Vimentin is involved in metabolism related to cancer. The evidence from this study also suggests that Vimentin could be used as a drug for cancer treatment. This study is the first step of developing a useful drug for cancer. 

  • Drug Chemistry | Medicinal Chemistry and Drug Discovery | Cancer Studies |Biochemistry | Targeted Drug Delivery System | New Trends in Pharmacology & Drug Development | Computer Aided Drug Designing-CADD
Location: Dallas , USA

Session Introduction

Jaein Ha

Korea University College of Medicine, Korea

Title: The Anticancer effect of a specific Myokine, Vimentin
Biography:

Jaein Ha is an Undergraduate student at Korea University College of Medicine. She has studied Organic Chemistry and is interested in the fields such as Bioorganic Chemistry and Pharmacology. Now, she is doing a research under her academic advisor, Kim, Hyeon Soo (Anatomy Department, Korea University College of Medicine). Her research interest is myokine, which is a molecule secreted from muscle cells. She tries to identify specific myokine which are associated with cell metabolism.
 

Abstract:

Myokines are known to suppress some kinds of tumor. This fact makes it possible to explain the correlation between physical activities and cancer. The researcher suggests that Vimentin, an intermediate filament, is a novel myokine and has an anticancer effect on pancreatic cancer. Vimentin was shown to be secreted from muscle cells by muscle contraction. Furthermore, Vimentin treatment on L6 cell increased phosphorylation of AMPK and ACC. These results imply that Vimentin is associated with signaling pathways regulating various metabolisms. MTT assay results demonstrated that Vimentin controls the viability of pancreatic cancer cell, MIA-Pa-Ca-2. The study provides considerable insight into role of Vimentin as a myokine. Muscle contraction leads to secretion and Vimentin is involved in metabolism related to cancer. The evidence from this study also suggests that Vimentin could be used as a drug for cancer treatment. This study is the first step of developing a useful drug for cancer. 

Biography:

Hongli Wu has completed her PhD from Peking University and Postdoctoral studies from the University of Nebraska-Lincoln. She is the Assistant of Pharmaceutical Sciences at the University of North Texas Health Science Center. She has published more than 25 papers in reputable journals

Abstract:

Age-related macular degeneration (AMD) is a leading cause of blindness worldwide. The lack of adequate AMD animal models and poorly understood pathogenesis have greatly hindered our progress in therapeutic development. To address these shortcomings, this project was designed to examine how retinal redox dysregulation leads to AMD and characterize glutaredoxin 2 (Grx2), a mitochondrial thiol redox regulating enzyme, knockout mice as a new animal model for AMD. We found that Grx2 KO mice developed age-dependent retinal degenerative pathology. By 12-month of age, Grx2 null mice showed ~50% decrease in a-wave and ~30% decline in b-wave amplitude (n=8, P<0.01). Histological analysis revealed extensive RPE lesions, including RPE atrophy, vacuolation, hyper- and hypo-pigmentation, sub-RPE deposits, and loss of tight junction integrity. Age-dependent lipofuscin accumulation was also observed in Grx2 KO mice. Furthermore, Grx2 KO mice demonstrated increased marker of mitochondrial oxidative damage including PSSG accumulation. In conclusion, Grx2 plays a critical role in maintaining the mitochondrial redox homeostasis in the aging retina. Grx2 deficiency causes PSSG accumulation and sensitizes RPE cells to age-related oxidative damage, leading to RPE degeneration and photoreceptor damage. As a new animal model for AMD, Grx2 KO mice will provide new insights into pathogenesis and therapeutics of AMD. Grx2 may serve as a new therapeutic target for AMD and the Grx2 activating drugs may be used to treat AMD. 

Biography:

Jung-Mo Ahn has received his PhD in Chemistry from the University of Arizona and completed his Postdoctoral studies in the Scripps Research Institute. He is Associate Professor in Chemistry at the University of Texas at Dallas and a Council Member of the American Peptide Society. His research mainly focuses on structure-based design of peptidomimetics targeting protein-protein interactions.

Abstract:

Protein-protein interactions are one of the fundamental processes that regulate numerous key cellular pathways. Since α-helical structures are frequently found on the interfaces of protein complexes, short helical peptides derived from such proteins have been considered as a valuable tool for research and clinical applications. However, peptides in general may suffer from drawbacks that can severely compromise their effective in vivo use, such as rapid enzymatic degradation, poor bioavailability, and lack of membrane permeability. Thus, small molecules that mimic functions of helical peptides would be of great interest in targeting and disrupting protein-protein interactions that take place inside cells. To the end, we have designed oligo-benzamides as versatile scaffolds to emulate protein helical surfaces. The rigid oligo-benzamide scaffolds can present multiple functional groups corresponding to the side chains found on one helical face. In addition to the outstanding α-helix mimicry, oligo-benzamides can be efficiently synthesized by following high-yielding and iterative steps in solution- and solid-phase. Nuclear receptors like androgen receptor and estrogen receptor recruit a variety of coactivator proteins to exert their functions, and many of the molecular recognition are triggered by consensus LXXLL motifs. We have designed oligobenzamides based on the sequence and structure of the helical LXXLL motifs, and they demonstrated utilities in disrupting NR-coactivator protein complex formation, inhibiting NR-mediated gene transcription, and blocking NR-mediated cell proliferation in prostate and breast cancer cell lines. These exciting results indicate that oligo-benzamides are effective tools to mimic functions of α-helices and may have a high potential in biomedical research.