A growing team of groundbreaking scientists around the world are now sharing their lab notebooks online
In a collaboration between SGC-University of North Carolina-Chapel Hill and M4K Pharma, we plan to synthesize 3 different imidazopyridin pyrazines as promiscuous kinase ALK2 inhibitors, compounds 1-3, Scheme 1. The first step will be the synthesis of key intermediate 10, Scheme 2. The proposed synthesis begins with a nucleophilic aromatic substitution on compound 4 to Read More …
In this post I’d like to return to looking at my work on phosphorylation. Phosphorylation is a key signalling method for activating the BMP pathway and inducing activity. Specifically activation of ALK2 by phosphorylation leads to phosphorylation of SMAD1 which leads to gene transcription that ultimately is responsible for bone formation. In this post I’m Read More …
Did you know as many as 30% of the cells in labs could be misidentified? And what a nightmare it would be to find out years of your work are just completely wrong because you got your skin cells mixed up with your brain cells… So to avoid that catastrophe, I took some time to Read More …
ZFYVE9C (Otherwise known as SARA) is a scaffold protein involved in the association of various protein components as part of the TGFB signalling pathway. The equivalent in the BMP signalling pathway is a protein known as Endofin so studying SARA (which is slightly easier) might give us useful insights for both proteins. For more details Read More …
I’ve not posted in a while, mainly because things have been really busy, but good busy, as I now have 3 new datasets/structures, of ALK2 with M4K2118, M4K2149 and, amazingly, M4K2009. As you know, this is our lead candidate, which until now has not behaved very well in crystal trials, and it hasn’t been possible Read More …
I thought I’d spend a blog post just talking about the various paths of my research and try and tie it all together. A lot of my experiments do dot around these various arms of investigation and so one experimental post doesn’t necessarily tie in directly with the previous one or the next one and Read More …
Further down the line I want to be able to test the activation of the BMP signalling pathway downstream of the ALK2 receptor. For this I plan to use the alkaline phosphatase gene as a readout – it’s a well known gene activated downstream of BMP signalling so a lot of easy to use assays Read More …
Hello everyone and happy New Year! I really, really wanted to end the year on a high note in December before I went off on holiday, but as it turned out, I didn’t have enough time to set up 18 plates and write a blog post on the last day. So I’ll just have to Read More …
In an effort to develop clinical compounds for Diffused Intrinsic Pontine Glioma (DIPG) treatment, new analogues of ACVR1/ALK2 inhibitors are continuously synthesised by Ontario Institute for Cancer Research (OICR) and Charles River Laboratories (CRL). I will provide prompt feedback of the cellular assay results to guide their design of new compounds. I determined the potency Read More …
One problem with working with the isolated kinase domains of ALK2 and it’s type II binding partners, is that the affinity between the kinase domains alone is insufficient to allow complex formation. We know that the two proteins associate with each other in vivo and are co-localised by the domains on the outside of the Read More …
