In writing the last post I had a query about the way 6-Mercaptopurine and 6-Thioguanine and their modes of action were similar and different. Not being a biochemist, not even a scientist, I wrote Patty to ask for some clarification but before she had a chance to reply, I found PharmGKB.
This is database project to pool pharmogenetic and pharmogenomic data to allow researchers open access to others' data on the mechanisms of drugs and the often different reactions that patients have to the drugs due to differences in their genetic make-up.
To quote from a downloadable paper explaining the project (available here – but I couldn't get it to open in Acrobat Reader and had to use KGhostView):
“The ultimate product of this project will be a knowledge base that will provide a public infrastructure for understanding how variations in the human genome lead to variations in clinical response to medications.”
The project uses XML schema for data to be structured with modifications to the schema being made available for review by participating researchers. It provides a Java API for uploading data which conforms to the Open Knowledge Base Connectivity standard (I'll have to do some more research on that). Data can be submitted via web-based forms or directly in XML following the project's schema. Integration with other external databases is another project aim with project data being made available freely. This requires the project to monitor closely the structure of the external databases to ensure efficient and maintainable data transfer. Sorry if that's a bit technical for non-geeks.
The project is based at Stanford University in the USA.
Anyway I found my answer about 6-MP and 6-TG here – not that I really understand it! But basically 6-TG follows a more direct approach to integrating with DNA than 6-MP. Why this should have resulted in higher mortality for 6-TG in the UKALL 1997 trial I really don't know.
Several other of our chemotherapy drugs are also on the site and I'm sure I'll be using the resource again.
Patty adds "From the schemes given, no, biochemically one can't see why. But the body is such a complex system, and although biochemists try to put everything into nice little pathways, the story is rarely that simple. I know that one CCG trial found a lot of liver toxicity with 6TG".