Aug
12
Mon
2013
Invited Talk: ColoAd1- An oncolytic adenovirus derived by directed evolution @ Acharya Hall
Aug 12 @ 2:07 pm – 2:30 pm

TerryHermistonTerry Hermiston, Ph.D.
Vice President, US Biologics Research Site Head, US Innovation Center Bayer Healthcare, USA


ColoAd1 – An oncolytic adenovirus derived by directed evolution

Attempts at developing oncolytic viruses have been primarily based on rational design. However, this approach has been met with limited success. An alternative approach employs directed evolution as a means of producing highly selective and potent anticancer viruses. In this method, viruses are grown under conditions that enrich and maximize viral diversity and then passaged under conditions meant to mimic those encountered in the human cancer microenvironment.  Using the “Directed Evolution” methodology, we have generated ColoAd1, a novel chimeric oncolytic adenovirus. In vitro, this virus demonstrated a >2 log increase in both potency and selectivity when compared to ONYX-015 on colon cancer cells. These results were further supported by in vivo and ex vivo studies. Importantly, these results have validated this methodology as a new general approach for deriving clinically-relevant, highly potent anti-cancer virotherapies.  This virus is currently in clinical trials as a novel treatment for cancer.

Terry (1) Terry (2)

Aug
13
Tue
2013
Plenary Talk: Biosensor and Single Cell Manipulation using Nanopipettes @ Amriteshwari Hall
Aug 13 @ 10:06 am – 10:49 am

NaderNader Pourmand, Ph.D.
Director, UCSC Genome Technology Center,University of California, Santa Cruz


Biosensor and Single Cell Manipulation using Nanopipettes

Approaching sub-cellular biological problems from an engineering perspective begs for the incorporation of electronic readouts. With their high sensitivity and low invasiveness, nanotechnology-based tools hold great promise for biochemical sensing and single-cell manipulation. During my talk I will discuss the incorporation of electrical measurements into nanopipette technology and present results showing the rapid and reversible response of these subcellular sensors  to different analytes such as antigens, ions and carbohydrates. In addition, I will present the development of a single-cell manipulation platform that uses a nanopipette in a scanning ion-conductive microscopy technique. We use this newly developed technology to position the nanopipette with nanoscale precision, and to inject and/or aspirate a minute amount of material to and from individual cells or organelle without comprising cell viability. Furthermore, if time permits, I will show our strategy for a new, single-cell DNA/ RNA sequencing technology that will potentially use nanopipette technology to analyze the minute amount of aspirated cellular material.

Invited Talk: Nanoscale Simulations – Tackling Form and Formulation Challenges in Drug Development and Drug Delivery @ Sathyam Hall
Aug 13 @ 2:15 pm – 2:40 pm

lalithaLalitha Subramanian, Ph.D.
Chief Scientific Officer & VP, Services at Scienomics, USA


Nanoscale Simulations – Tackling Form and Formulation Challenges in Drug Development and Drug Delivery

Lalitha Subramanian, Dora Spyriouni, Andreas Bick, Sabine Schweizer, and Xenophon Krokidis Scienomics

The discovery of a compound which is potent in activity against a target is a major milestone in Pharmaceutical and Biotech industry. However, a potent compound is only effective as a therapeutic agent when it can be administered such that the optimal quantity is transported to the site of action at an optimal rate. The active pharmaceutical ingredient (API) has to be tested for its physicochemical properties before the appropriate dosage form and formulation can be designed. Some of the commonly evaluated parameters are crystal forms and polymorphs, solubility, dissolution behavior, stability, partition coefficient, water sorption behavior, surface properties, particle size and shape, etc. Pharmaceutical development teams face the challenge of quickly and efficiently determining a number of properties with small quantities of the expensive candidate compounds. Recently the trend has been to screen these properties as early as possible and often the candidate compounds are not available in sufficient quantities. Increasingly, these teams are leveraging nanoscale simulations similar to those employed by drug discovery teams for several decades. Nanoscale simulations are used to predict the behavior using very little experimental data and only if this is promising further experiments are done. Another aspect where nanoscale simulations are being used in drug development and drug delivery is to get insights into the behavior of the system so that process failures can be remediated and formulation performance can be improved. Thus, the predictive screening and the in-depth understanding leads to experimental efficiency resulting in far-reaching business impacts.

With specific examples, this talk will focus on the different types of nanoscale simulations used to predict properties of the API in excipients and also provide insight into system behavior as a function of shelf life, temperature, mechanical stress, etc.

Delegate Talk: Pharmacophore modeling, atom-based 3D-QSAR and molecular docking studies on Pyrimido[5,4-e][1,2,4]triazine derivatives as PLK 1 inhibitors @ Sathyam Hall
Aug 13 @ 3:55 pm – 4:10 pm
Delegate Talk: Pharmacophore modeling, atom-based 3D-QSAR and molecular docking studies on Pyrimido[5,4-e][1,2,4]triazine derivatives as PLK 1 inhibitors @ Sathyam Hall | Vallikavu | Kerala | India

Rajasekhar Chekkara, Venkata Reddy Gorla and Sobha Rani Tenkayala


Pharmacophore modeling, atom-based 3D-QSAR and molecular docking studies on Pyrimido[5,4-e][1,2,4]triazine derivatives as PLK 1 inhibitors

Polo-like kinase 1 (PLK1) is a significant enzyme with diverse biological actions in cell cycle progression, specifically mitosis. Suppression of PLK1 activity by small molecule inhibitors has been shown to inhibit cancer, being BI 2536 one of the most potent active inhibitor of PLK1 mechanism. Pharmacophore modeling, atom-based 3D-QSAR and molecular docking studies were carried out for a set of 54 compounds belonging to Pyrimido[5,4-e][1,2,4]triazine derivatives as PLK1 inhibitors. A six-point pharmacophoremodel AAADDR, with three hydrogen bond acceptors (A), two hydrogen bond donors (D) and one aromatic ring (R) was developed by Phase module of Schrdinger suite Maestro 9. The generated pharmacophore model was used to derive a predictive atom-based 3D quantitative structure-activity relationship analysis (3D-QSAR) model for the training set (r2 = 0.88, SD = 0.21, F = 57.7, N = 44) and for test set (Q2 = 0.51, RMSE = 0.41, PearsonR = 0.79, N = 10). The original set of compounds were docked into the binding site of PLK1 using Glide and the active residues of the binding site were analyzed. The most active compound H18 interacted with active residues Leu 59, Cys133 (glide score = −10.07) and in comparison of BI 2536, which interacted with active residues Leu 59, Cys133 (glide score = −10.02). The 3D-QSAR model suggests that hydrophobic and electron-withdrawing groups are essential for PLK1 inhibitory activity. The docking results describes the hydrogen bond interactions with active residues of these compounds. These results which may support in the design and development of novel PLK1 inhibitors.