Recent Experiments

Release of brachyury (TBXT) SPR Raw Data

This week we released our Surface Plasmon Resonance (SPR) data for the binding of small molecules to brachyury (gene name TBXT) on Zenodo (https://doi.org/10.5281/zenodo.6394811).  The raw data was collected by HD Biosciences as part of an ongoing campaign to identify potent ligands of this transcription factor that is critically important to chordoma cells. This upload Read More …

TBXT ligands for Chordoma: Thiazoles for pocket A’

During our initial fragment screen for brachyury, we identified two fragments that bound to pocket A’. These two structures can be found in the Protein Data Base (pdb) with codes: 5QS9 and 5QSD. To date, this site and the derivatives of these two fragments represent some of our most promising targets for targeting brachyury. In Read More …

Tandem Microwave-Facilitated Synthesis of Ether-Containing Oxadiazoles

Tandem Microwave-Facilitated Synthesis of Ether-Containing Oxadiazoles David A. Rogers and Kevin J. Frankowski https://doi.org/10.5281/zenodo.6036677 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 the goals of TREAT-AD is to create Read More …

Taking Aim and Firing at TBXT to Combat Chordoma

Hello! My name is Nergis Imprachim and I am working at CMD, University of Oxford. I am working on drug discovery projects– one of them focuses on targeting T-box transcription factor T (TBXT) that is associated with chordoma. Chordoma is a bone cancer affecting the skull base and spinal cord. It is a slow-growing, rare Read More …

TBXT ligands for Chordoma: lactams for pocket F

Our initial fragment screen identified four different fragments that bound to what we call site F (Figure 1) These can be found in the Protein Data Base (pdb) with these codes: 5QSA, 5QSC, 5QSI, and 5QSK. In this blog I will talk about some observations from these structures that suggest promise for this pocket, show Read More …

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 …