Question

Two drug candidates were tested in a cell-based assay. Addition of drug candidate 1 resulted in an increase in intracellular cAMP. Addition of drug candidate 2 also resulted in an increase in cAMP Chemical and structural analysis indicated that both drug candidates have a doubly hydroxylated benzene ring that is connected to a linear -C(OHH)-C(H2)-NH-CH3 tail. Interestingly, drug candidate 1 produced even more dramatic increases in cAMP levels when co-administered with a cyclic nucleotide phosphodiesterase inhibitor. This effect was not observed for drug candidate 2. Addition of drug candidate 1 also increased the phosphorylation status of key cellular signaling proteins. This effect was not observed for drug candidate 2. Based on this data and material presented in lecture, what receptor do you think drug candidate 1 is acting on? Do you think drug candidate 2 is acting on the same receptor. Assuming satisfaction of the Lipinski rules reliably predicts oral bio-availability, would you predict drug candidate 1 to be orally active? Please support your answers with facts and logical arguments. subject: computitional biochemistry

Answer 1

Solution:

From the analysis of the given data in question its clear both the drug 1 and drug 2 are competiting for the same receptor, in simple drug 1 and drug 2 are competitive in nature, the increased activity of cAMP in drug 1 is due to ligand affinity to the receptor on comparing with drug 2.

When comes to activity of drug while administering orally is not suitable for drug 1 as it's having more than 5 hydrogen atoms to donate for hydrogen bonding, its violating lipinski rule, so drug 1 is not suitable for oral administration.