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 …

Determining the nanoBRET ALK2 IC50 values of 24 new ACVR1/ALK2 inhibitors

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 …

Synthesis and testing of follow up compounds based on HAO1 fragment 6, bound at the tetramer interface.

Hello again! A few posts ago (here), I presented one fragment bound at the interface between two subunits of the HAO1 tetramer (figure 1 will refresh your memory). Our idea to optimize this fragment into an inhibitor would be to make it bigger so that it disrupts the HAO1 tetramer. I would expect this to Read More …

Purification and crystallisation of an ALK2/ACVR2/FKPB12 complex.

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 …

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 …

Validated antibodies for ALS research: the ALS-RAP project

We are part of ALS-RAP, the ALS (Amyotrophic Lateral Sclerosis) Reproducible Antibody Platform. We’re addressing one of the big conundrums to biomedical research: the lack, or the poor quality, of many antibodies used for research ranging from cell biology to histopathology. ALS, also called MND (motor neurone disease), is a group of diseases that cause Read More …