Drug–receptor interaction has fascinated researchers since antiquity. It has been evolved from a concept of “Lock and Key” to the use of Furchgott's method (1966) to quantify dissociation constants and relative efficacies of agonist–receptor complexes. In the last 40 years, great strides in developments in molecular pharmacology have resulted in the accumulation of a vast amount of knowledge. This article briefly summarizes the recent developments in drug–receptor interactions with focus on inverse agonism and its potential therapeutic utility.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3195115/

For the RORgamma transcription factor I would definitely choose a functional assay like cytokine release (for example IL-17 release from Th17 cell, etc) or proliferation of appropriate cells, depending on your system studied. You should establish a measurable basal activity in your assay and look for the decrease of this activity due to the treatment with compounds in interest. I think binding assays developed for the ligand binding domain of RORs are not meaningful for inverse agonism.

Cheers, Karoly

Dear Dr. Karoly Liliom,

Thank you so much for your reply.

Regarding functional assay of IL17 inhibition, how can we differentiate the antagonist and inverse agonist. Because both will inhibit the IL17 production. 

Please let me know your thoughts.

Regards,

Kolla