Question

MEK is second messenger. Second messengers transmit and amplify the signal received by receptor –ligand interactions on the outside of the cell. Assume that the cancer cell has a mutation causing a constitutively active MEK (on all the time). Design a drug that acts as either a competitive inhibitor, allosteric inhibitor, or antagonist that would specifically inhibit this phenotype. Explain the Kd/Km of your drug for your chosen target. Explain the type of inhibition you will use. Explain how your drug will decrease the activity or MEK or decrease the amount of activated MEK in the cell.

Answer 1

MEK (MAPK-ERK-KINAS - Mitogen activated protein kinase-extracellular signal-regulated kinases-kinase) is a secondary messenger in the RTK (receptor tyrosine signalling) signalling. RTK signalling is upregulated in cancer cells, which means MEK is also upregulated. MEK is activated upon phosphorylation by RAF Kinase (rapidly accelerated fibrosarcoma kinase).

To deactivate the activity of MEK, a drug can be designed such that which can dephosphorylate the activated MEK. Upon dephosphorylation MEK is inactivated and the MEK signalling is ceased. As a result, the cancerous growth is stopped.

Anatagonist type of drug (inhibitor) can be used to inhibit the activity of RAF kinase. As the name suggests , antagonist acts against the natural ligands. Antagonist binds to the same active site of the enzyme where, the original ligand binds, and decrease the affinity of original substrate. The Km (Michaelis constant) of the drug thus would be lower for the RAF Kinase, as the lower the value of Km, higher will be its affinity.