How ALK Inhibitors work

ALK inhibitors work by interfering with (or inhibiting) the ALK signaling pathway.  One way to think of how a signaling pathway works is to think of it as a series of locks and keys.  In order to pass a signal from one kinase (the key) to another kinase (the lock) the two kinases need to temporarily fit together. A kinase inhibitor works by temporarily blocking the lock, so that the key can not fit. Thus a certain concentration of kinase inhibitors has to be reached in order to block the signal from being passed sufficiently often (probably over 90%) in order to stop the kinase from regulating the expression of certain genes.

Most of the drugs that are being developed to combat ALK based tumors are designed to interfere with (or inhibit) ALK’s signaling pathway (either by stoping ALK from passing a signal or stopping another kinase in the pathway from passing its signal). So for example GSK-2141795 is designed to inhibit the AKT kinase which is downstream from ALK. Thus it is being tested to see if it is effective against ALK based tumors along with other types of tumors.

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