Recent Experiments

TBXT Ligands for Chordoma: Priority series molecules

Our chordoma research focused on developing small reversible molecules targeting the transcription factor TBXT which codes for the brachyury protein. Brachyury contains several shallow pockets, and through an x-ray crystallography fragment based approach we previously identified several series of small fragments bound to it (TBXT Fragment Hits). Our medicinal chemistry project aimed to grow the Read More …

In vivo characterization of antibodies directed against TREAT-AD target proteins in mouse model of AD pathology

In vivo characterization of antibodies directed against TREAT-AD target proteins in mouse model of AD pathology Suzanne Doolen, Riham Ayoubi, Carl Laflamme, Ranjita Betarbet, Elizabeth Zoeller, Sean-Paul G. Williams and Stacey J. Sukoff Rizzo https://doi.org/10.5281/zenodo.6612215 Our goal in support of the Emory-Sage-Structural Genomics Consortium (SGC) TREAT-AD Center is to develop and identify high-quality tools to Read More …

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 …