A growing team of groundbreaking scientists around the world are now sharing their lab notebooks online
Background: Evaluation of the efficacy of M4K compounds in DIPG patient-derived cell lines is essential before any promising compounds can be further tested in mouse xenograft models. This approach can aid in narrowing down clinical compound candidates and reduce the time, resources and animal sacrifice needed downstream. A robust and efficient readout for the changes Read More …
Continuing with our goal to synthesize three compounds as ALK2 inhibitors, let’s refer back to Scheme 2 in the previous post on this topic, compounds 6, 8 and 9 were synthesized in good yields (65-90%), however compound 10 could not be obtained. Different conditions were tested to induce the cyclization of the bromo-pyrazine-2-carboxamide 9 Read More …
The molecular blueprint of the living organisms, deoxyribonucleic acid (DNA), is often wrapped with a family of proteins, called histones, in mammalian cells. The functions of histones are vast, including the protection of DNA, and most importantly, the regulation of gene expression. However, the details of gene regulation function of histones are not clearly understood, Read More …
Huntington’s disease (HD) is a progressive neurological disorder caused by a mutation in the HTT gene which encodes for the huntingtin protein. The current understanding of the function of HTT is limited, and there are only a few sources that indicate that it likely plays a critical role in several intracellular processes such as Read More …
I have been busy in the lab working at the bench and training our new recruits to the Huntington’s disease research team! Welcome Jacob and Claudia! Using a technique called BioID, we have identified proteins which are proximal or nearby to the HTT protein in cells. To date, no published literature details the use of Read More …
Following up on the crystals from my last post I sent them along on the last Diamond trip we had to beamline I04 but regrettably didn’t get any usable datasets. Perhaps fortunately there is a possible explanation for this that isn’t just ‘the crystals were a bit too rubbish’. We send our crystals to the Diamond Read More …
Hello again. My apologies for the delay in posting – I’ve been busy with other projects lately. As a follow up to my previous post, we wanted to further confirm our EZH1 antibody and test it in a knockout line. To do this, we generated a CRISPR knockout of EZH1 in an AML cell line Read More …
In a previous post, I tested hit analogues and found compound XSR00035795a (Figure 1) had increased potency and ligand efficiency; however, compound XSR00035795a was also found to bind to HDAC6 Zf-UBD, so it was not selective towards USP5. Figure 1. XSR00035795a We hypothesized that it was possible to extend the aliphatic group on the carboxylic Read More …
Stem cells are a set of cells that, unlike most cells in the body, can divide as many times as they want, and can turn into any cell in the body. The mutations in cancer often make the cells behave more like stem cells, because in order to grow into a large tumour they may Read More …
In order to develop ligands addressing different possible binding sites of the transcription factor brachyury, fragments co-crystallized with this protein should be developed into ligands by using the program SparkTM (Cresset®). Brachyury (T, TBXT) is an essential regulator of the notochord development. Brachyury is primarily expressed in the embryo but not in the majority of normal Read More …
