TZP-201

TZP-201 is a synthetic, macrocyclic small-molecule antagonist of the motilin receptor, originally developed by Tranzyme Pharma using its proprietary Macrocyclic Template Chemistry (MATCH) platform. The drug was specifically designed to address gastrointestinal motility disorders, with a primary focus on chemotherapy-induced diarrhea (CID), particularly the severe diarrhea associated with irinotecan treatment. By selectively blocking the motilin receptor, TZP-201 inhibits motilin-induced contractile activity in the colon, thereby reducing the excessive intestinal motility that leads to diarrhea. In preclinical studies involving beagle dogs and musk shrews, TZP-201 demonstrated high efficacy in preventing diarrhea and reducing stool frequency, showing superior performance compared to standard-of-care treatments such as loperamide and octreotide. Despite its preclinical promise, the development of TZP-201 appears to have been discontinued following corporate transitions at Tranzyme Pharma.