Macrophage Tropism and Antibody Neutralization Resistance of HIV-1 is Conferred by the Envelope Protein gp120

This MQP investigated the viral tropism and neutralizing antibody sensitivities of gp120 and gp41 sequences of three parental HIV-1 strains (Q43-378.2, Q43-378.c, and SQ43-380.1) isolated from a single patient, and of various engineered chimeras. The data indicate that gp120 alone is able to confer macrophage tropism, while gp41 has no noticeable effect on tropism. The data further indicate that gp41 has no visible effect on the resistance to a b12 antibody that reacts with the CD4-binding domain on gp-120, and that gp120 sequences are the most likely cause of neutralization resistance

Stem Cells

Stem cell research is a controversial topic that strongly affects society, but misinformation to the public complicates the issue. This IQP clarifies the types and sources of stem cells, discusses their applications, and outlines the religious and political opposition that make support for the research difficult. We hope the public will read this report open mindedly to formulate their own educated opinion on this complex topic

Discovery of Novel, Induced-Pocket Binding Oxazolidinones as Potent, Selective, and Orally Bioavailable Tankyrase Inhibitors

Tankyrase (TNKS) is a poly-ADP-ribosylating protein (PARP) whose activity suppresses cellular axin protein levels and elevates β-catenin concentrations, resulting in increased oncogene expression. The inhibition of tankyrase (TNKS1 and 2) may reduce the levels of β-catenin-mediated transcription and inhibit tumorigenesis. Compound <b>1</b> is a previously described moderately potent tankyrase inhibitor that suffers from poor pharmacokinetic properties. Herein, we describe the utilization of structure-based design and molecular modeling toward novel, potent, and selective tankyrase inhibitors with improved pharmacokinetic properties (<b>39</b>, <b>40</b>)

Development of Novel Dual Binders as Potent, Selective, and Orally Bioavailable Tankyrase Inhibitors

Tankyrases (TNKS1 and TNKS2) are proteins in the poly ADP-ribose polymerase (PARP) family. They have been shown to directly bind to axin proteins, which negatively regulate the Wnt pathway by promoting β-catenin degradation. Inhibition of tankyrases may offer a novel approach to the treatment of <i>APC</i>-mutant colorectal cancer. Hit compound <b>8</b> was identified as an inhibitor of tankyrases through a combination of substructure searching of the Amgen compound collection based on a minimal binding pharmacophore hypothesis and high-throughput screening. Herein we report the structure- and property-based optimization of compound <b>8</b> leading to the identification of more potent and selective tankyrase inhibitors <b>22</b> and <b>49</b> with improved pharmacokinetic properties in rodents, which are well suited as tool compounds for further in vivo validation studies