How are drugs designed?

This is a huge topic, but I want to point out an example that I was very concerned about when I was an undergraduate (undoubtedly very close to the views of hematologists such as TC Quah).

In 200 1 year, FDA approved STI-57 1 for the treatment of a famous leukemia. This form is famous because it is relatively common (in the United States, one in every 526 people will get this disease in their lifetime) and has been fully studied. As we all know, there are Philadelphia chromosomes in almost all cases-Philadelphia chromosomes are named after the cities where David Hungerford and Peter Naur worked.

As a biochemical research, this is very important to me, because one of the protein products of Philadelphia chromosome is P2 10, the Frankenstein monster of tyrosine kinase, and this bad guy destroys many signal pathways involved in cell replication. I'm particularly interested in JAK/ statistics.

Nicholas Lydon's team in Ciba-Geigy (later acquired by Novartis) has been working on tyrosine kinase inhibitors since 1990s. Through sti57 1, they discovered biochemical gold. As a competitive inhibitor of BCR-ABL protein products, the drug later called imatinib effectively shut down the kinase activity.

This is almost a breakthrough in cancer treatment. Levich changed the treatment of chronic myeloid leukemia. For example, 3 1 subjects in the first phase of the trial all entered the remission period.

As Brian Drucker of Oregon said at the time, "This is almost unheard of in phase I clinical trials." Usually in the first phase of clinical trials, if you see a remission rate of 20%, that would be great. We have a drug that is well tolerated and the remission rate is 100%. It's incredible to see this scene. "

Therefore, to some extent, Gleevec represents the beginning of the "modern era" of molecular drug design-the physical characteristics of biochemical agents can be used for modeling and subsequent synthesis.

Around the beginning of last century, in the dial-up Internet era, some of us "donated" cpu components to make networked "supercomputers". This is used by the protein Folding Project to speed up digital operations.

Now we have Foldit. It has even been used in the treatment of coronavirus pneumonia-19.