Pharmaceutical Testing and Development


C188-9 STAT3 Inhibitor – Technology Overview

Stat3 plays a central role in breast cancer stem cell development and has been validated as a drug target in these cells, as well as in the treatment of TNBC, for which no targeted therapy exists. StemMed used computer-based docking to screen 920,000 compounds and identified three small-molecule probes that targeted the phosphotyrosyl peptide-binding pocket within the Src homology 2 domain of Stat3. The most active probe, C188, reduced TNBC PDX tumor volumes and improved tumor-free survival of engrafted mice 4-fold when used in combination with standard chemotherapy. StemMed performed 2-D similarity screening, 3-D pharmacophore analysis, and 3-rounds of structure-activity relationship (SAR)-directed medicinal chemistry to identify C188-9, its lead, first-in-class drug for targeted treatment of TNBC.

StemMed has compelling pre-clinical results using cancer cell line xenograft models that also support the use of C188-9 either alone or with radiation therapy in patients with non-small cell lung cancer and head and neck squamous cell cancer. In addition, results from mouse pre-clinical models support its use in patients with cachexia secondary to cancer or chronic kidney disease, as well as in patients with idiopathic pulmonary fibrosis, scleroderma, inflammatory bowel disease, asthma, or immediate-type hypersensitivity reactions.