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 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.