TA-DZE probe 21 was rationally designed based on our minimalist trifunctional monomer 14 and the required TA pharmacophore of the SR9009 agonist (Figure ). Amide coupling of SR9009 synthetic agonist core with DZE trifunctional monomer 14 followed by Boc-deprotection delivered the desired probe 21 in high yields (49% for two steps). To confirm that the newly designed and synthesized TA-DZE probe 21 retains desired pharmacological properties, the probe was screened along with parent compounds SR9009 and SR9011 in a previously reported Th17 differentiation assay on primary cells. Primary human CD4 T cells were cultured under Th17 differentiation conditions with or without compounds (DMSO, SR9009, SR9011 and TA-DZE probe 21). Similar to parent compounds SR9009 and SR9011, TA-DZE probe 21 treatment inhibits Th17 differentiation (Figure ).