501derful.org
This is interesting not just because it’s a promising new development in cancer treatment but because it was done using techniques that seem to be a modest advance in tools that might make drug design more cost effective.
This new agent works by inhibiting a fundamental signaling point in cancer cells, making it potentially effective in a wide range of cancer types,” says study leader Ching-Shih Chen… We also have evidence that it may sensitize leukemia, and breast and lung cancers to conventional chemotherapy…Scientists knew from the start that celecoxib helps control inflammation by inhibiting an enzyme known as cyclooxygenase-2 (COX-2). But they couldn’t explain the drug’s modest anti-cancer activity…Past work led by Chen provided the answer. “We found that celecoxib’s ability to cause cell death and to control inflammation were two different pharmacological properties, and that the two properties could be separated,” Chen says.
Great, but this is the part I find most interesting:
For this study, Chen and his colleagues used molecular-modeling methods and computational chemistry to alter celecoxib’s basic molecular structure in ways calculated to maximize its Akt-blocking and cell-death inducing activities. This work generated a series of derivative molecules, all of which were far different in structure from celecoxib. Two of these proved to be 30 to 50 times more potent than celecoxib in inducing programmed cell death in cancer cells growing in the laboratory tests.
This is the “rational design” way drug developers would like to work all the time—use some nifty but accurate computer modeling—but it has been disappointing in the past.
