Are Enantiomer of Chemical Probes Good Negative Controls?

Chemical probes typically bind off targets in addition to their intended target protein. Since it is hard to determine whether the phenotype is due to inhibition of the target protein or off-targets, the use of negative controls, which are structurally close to the probe but are inactive against the intended target, is highly recommended. Loss Read More …

Differential Expression of CD44 Variants in Normal and AD Brain

 Kun Qian, Ranjita Betarbet, Rachel Commander, Erik Johnson, Opher Gileadi, Haian Fu, and Allan Levey https://doi.org/10.5281/zenodo.4900586 Alzheimer’s disease (AD) is a progressive neurodegenerative disorder, characterized by two pathological hallmarks – extracellular amyloid plaques that are made up of amyloid-peptide and intracellular neurofibrillary tangles that are comprised of hyperphosphorylated tau. AD neuropathology, however, begins decades before Read More …

Fused tetrahydroquinolines (THQ): potential PAINS compounds in a recent HTS for moesin-CD44 pathway inhibitors

Joel K. Annor-Gyamfi, Felix Nwogbo, Kun Qian, Yuhong Du, Kenneth H. Pearce Jr, Opher Gileadi, Haian Fu, Stephen V. Frye and Alison D. Axtman https://doi.org/10.5281/zenodo.4685122 Alzheimer’s disease (AD) is the most common cause of dementia worldwide but very few therapeutic options exist despite multiple high-profile but failed clinical trials. And as the population of the Read More …

Distinguishing between catalytic and non-catalytic pockets in the ligandable human genome: InterPro analysis

As describe in my previous post, my goal is to discover non-catalytic druggable pockets in human enzymes. These pockets could potentially be exploited for the design of ProxPharm compounds (chimeric compounds that bring two proteins in close proximity to elicit an effect of one protein on the other1). An essential aspect for the design of Read More …

The Preparation of Allosteric SYK Inhibitor X1 and Investigation of a Covalent Inhibition Mechanism

Frances M. Potjewyd and Vittorio Katis http://doi.org/10.5281/zenodo.4670214 Spleen Tyrosine Kinase (SYK) has a reported role in AD pathology and was identified as a target for the TREAT-AD (Target Enablement to Accelerate Therapy Development for Alzheimer’s Disease) program.1–3 We are focusing drug discovery efforts on the inhibition of SYK and more specifically, inhibition of the interaction Read More …

Preparation of the Soluble Epoxide Inhibitor SWE101 and the DOCK1 inhibitor TBOPP

Preparation of the Soluble Epoxide Inhibitor SWE101 and the DOCK1 inhibitor TBOPP David A. Rogers and Kevin J. Frankowski https://doi.org/10.5281/zenodo.4637834 The National Institute on Aging has made a significant commitment to improving the treatment of Alzheimer’s disease through the funding of the TREAT-AD network (Target Enablement to Accelerate Therapy Development for AD, https://treatad.org/). One of Read More …

Druggability and Amino Acid Variability of the Catalytic Site of SARS-CoV-2 Nsp15 Across Coronaviruses and SARS-CoV-2 Samples – Post 26

Today’s post focuses on another protein encoded by many coronaviruses, the non-structural protein 15 (nsp15), an endoribonuclease. Nsp15 is a nidoviral RNA uridylate-specific endoribonuclease (NendoU) with C-terminal catalytic activity. This protein belongs to the EndoU family, and they all carry an RNA endonuclease activity to produce 2’-3’ cyclic phosphodiester and 5’-hydroxyl termini. (Kim et al. Read More …

Druggability and Genetic Variability at nsp9 Peptide-bound Pockets and Beta-barrel Pockets Across Coronaviruses and SARS-CoV-2 Samples – Post 25

Today’s post focuses on another protein encoded in open reading frame 1a (ORF1a) of many coronaviruses, the non-structural protein 9 (nsp9). Nsp9 is thought to mediate viral replication. In SARS-CoV-1, nsp9’s role has been highlighted as a single-stranded RNA-binding subunit. (Egloff et al., 2004) The structure of SARS-CoV-2 nsp9 was solved in both apo and Read More …