Ponatinib is an anti-cancer drug which has earned some notoriety for its cost (£90,000 per patient per year) and side-effects that were serious enough to temporarily suspend its use. But the findings from a recent Cell Chemistry and Biology paper led by the Structural Genomics Consortium suggest that this 'dirty' drug might actually hold the key for coming up with newer, more effective drugs for chronic illnesses such as Crohn's and Inflammatory Bowel Disease.
The Oxford Science Blog asked the first author, Dr Peter Canning (who worked on this study while at the Nuffield Department of Medicine) to explain what they found.
The SGC is engaged in dozens of collaborations with small companies to explore novel technologies. In keeping with the SGC’s open-access policy, all outputs from these collaboration are made publicly available without restriction on use. As announced today, the SGC in Oxford is collaborating with C4X to discover chemical tools for epigenetic targets. C4X will use its unique ligand conformation analysis technology to design potent inhibitors that will be tested at the SGC and rapidly made available to the public.
Ellie Williams has won the poster prize for the Biochemical Society's 78th Harden Conference: Protein Kinases in Health and Disease. She presented the recent work she and her colleagues have done investigating a pre-clinical compound (K04284) that may have applications in the rare disease Fibrodisplasia Ossificans Progressiva (FOP). FOP is caused by a single point mutation in the ALK2 kinase leading to uncontrolled bone formation and there is currently no treatment. K04284 is already in Phase 2 clinical trials for the treatment of some cancers and its additional activity against ALK2 provides exciting potential for fast track clinical trials for FOP.
Through a novel open source approach the molecule has been made freely available to the cancer research community to help discover new therapeutic strategies for cancer patients sooner.
Professors Markus Perkmann from Imperial College London and Henri Schildt of Aalto University School of Business report on their findings in the journal Research Policy on managing open data partnerships and the role of boundary organizations such as the SGC.
Markus Perkmanna & Henri Schildt
WD Repeat domain 5 (WDR5) is a critical part of the human trithorax/COMPASS complexes which are responsible for methylation of lysine 4 on histone 3 (H3K4) via one of several catalytic subunits, Mixed-Lineage Leukemia (MLL), MLL2, MLL3, or MLL4 proteins. Early hypotheses that antagonism of the MLL-WDR5 interaction might lead to reduction of H3K4 methylation encouraged us to search for small-molecule inhibitors of this interaction (PubMed 22989411). More recently, through a collaboration with the Ontario Institute for Cancer Research (OICR) we developed the chemical probe, OICR-9429, a potent, selective, and cell-penetrant WDR5 antagonist. Treatment of normal cells with OICR-9429 indicates that this compound disrupts the MLL-WDR5 interaction in a dose-dependent fashion.
Bromo and extra-terminal (BET) proteins tether the transcriptional machinery to chromatin, stimulating programmes that are often hijacked in disease.