Jong Fu Wong

Background: The binding potency of M4K compounds to ALK2 has been assayed in biochemical assay and cellular assays in HEK293 or C2C12 myoblast cell lines. However, the potency of ALK2 inhibition by M4K compounds has not determined directly in DIPG patient-derived cell lines. While no major deviation from existing assay data is expected, direct experimental Read More …

Background: I have been characterising the cellular potency of many M4K compounds against ALK2 and ALK5. Compounds that targets ALK2 and not ALK5 should be further evaluated for their ability to reduce the viability of cells derived from DIPG patients. Although these cultured cells might not reflect what actually happens in a DIPG patient’s brain, Read More …

Background: Aside from determining the optimal numbers of DIPG cells to be seeded for viability assay, it is also important to validate that measurements using CellTiter Glo are in agreement with other methods of determining cell viability. Experimental design: I chose to compare the EC50 values of M4K2009 on HSJD-DIPG-007 when measured using different methods. Read More …

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 …

Special thanks to: David Drewry – Helped with designing the nanoBRET tracers M4K pharma OICR chemist team – Synthesised the M4K1046-linker derivatives Carrow Wells (UNC) – Conjugated the M4K1046 to nanoBRET fluorophore Background: I have always wanted to establish nanoBRET target engagement assay for ALK5. Relative to dual luciferase promoter assay and immunofluorescent staining, nanoBRET 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 …

A large number of ACVR1/ALK2 inhibitors were previously synthesised by Paul Brenner’s team (Target Discovery Center, University of Oxford) for the purpose of treating Fibrodysplasia Ossificans Progressiva (FOP). Although these compounds were not designed with blood-brain-barrier permeability in mind, they can serve as good bench-marks for my cellular assays. Therefore, 30 of these legacy compounds Read More …

Dear readers, I had unfortunately torn my ACL for the silliest of reasons and have decided to use up my annual leaves for more time off. I will therefore be on hiatus till October. Adios! Jong Fu

A large number of ACVR1/ALK2 inhibitors were previously synthesised by Paul Brenner’s team (Target Discovery Center, University of Oxford) for the purpose of treating Fibrodysplasia Ossificans Progressiva (FOP). Although these compounds were not designed with blood-brain-barrier permeability in mind, they can serve as good bench-marks for my cellular assays. Therefore, 30 of these legacy compounds Read More …