Growing co-crystallized fragments to ligands of the transcription factor brachyury (T)

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 …

Synthesis of promiscuous ALK2 inhibitors

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 …

Checking I haven’t got my cells mixed up…

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 …

Quinazoline Series: Synthesis

We have received some very interesting biological data for our CaMKK2 inhibitor series (furopyridine, Azaindole and quinoline) and I will be sharing the data in the coming weeks, but before that, I wanted to share my synthetic efforts towards our quinoline series. Synthesis of Quinoline series: Starting with 6-Bromo-4-chloroquinoline, a two (2) step synthetic scheme Read More …

Optimising seeding of normal and FOP cells for a later assay – prettier than expected

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 …

Selective CDKL2 inhibitors – molecular modeling

At SGC we are interested in developing protein kinase inhibitors with a high selectivity towards other protein kinases. Based on lead compounds from the literature and our group new and selective CDKL2 inhibitors should be designed, synthesized and tested. Carla Alamillo, a former member of our group, worked on this topic and mentioned in her Read More …

Shorter procedure to access Thieno[2,3-d]pyrimidines

Continuing with the line of delivering a chemical probe for DRAK2/STK17B kinase, we decided to revise the procedure to synthesize analogs with a thieno[2,3-d]pyrimidine core, which are intended to be used as negative control in our DRAK2 inhibition study. We shortened the synthesis of these pyrimidines to 2 steps from the starting material 6-bromo-4-chlorothieno[2,3-d]pyrimidine 1 Read More …

Screening ACVR1 inhibitors on mutant and non-mutant ACVR1 DIPG cells – effectiveness may vary

Hi there! The last month of my life was taken over by making sure my PhD first year report was beautifully polished, but I have returned with results of a small compound screen: These are all compounds that Jong Fu has already tested with his assays so we know they effectively inhibit ACVR1, but I Read More …