Small molecule probe for IBD risk variant GPR65 I231L alters cytokine signaling networks through positive allosteric modulation
BRD5075 is a positive allosteric modulator of GPR65. Activity has been demonstrated by cAMP production in HeLa cells overexpessing GPR65 and target engagment has been confirmed. BRD5075 also decreases TNF-a secretion by GPR65 WT BMDCs. Goal is to identify differentially expressed genes in response to this GPR65 PAM Overall design: Total 90 samples. GPR65 WT, variant I231L, and KO BMDCs stimulated with different pH and GPR65 PAM in triplicate on the same plate for each timepoint (2 hours and 6 hours). Positive control is PGE2, negative is DMSO.