Drugging "undruggable" Disease-causing Proteins: Focus on Signal Transducer and Activator of Transcription (stat) 3.
Year: 2022
Type: article
Abstract: Signal transducer and activator of transcription (STAT) 3 has been assigned to the group of "undruggable" disease-causing proteins, despite its containing a Src-homology (SH) 2 domain, a potential Achilles' heel that has eluded successful targeting by academic and pharmaceutical groups over the past 30 years. Based on mutational and modeling studies, our group developed a unique virtual ligand screening strategy targeting the STAT3 SH2 domain that was coupled to robust biochemical and cellular assays and structure-based medicinal chemistry and led to the identification of TTI-101. TTI-101 represents one of the most advanced, direct, small-molecule inhibitors of an SH2 domain-containing, disease-causing protein in clinical development. TTI-101 is currently being evaluated in a Phase 1 study to determine safety and tolerability in addition to pharmacodynamic effects and efficacy in patients with advanced solid tumors.
Source: PubMed Central
Author: David J Tweardy
Language: English
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: green
Funder: National Cancer Institute
Awards: MD Anderson Cancer Center SPORE in Gastrointestinal Cancer, The University of Texas MD Anderson Cancer Center SPORE in Hepatocellular Carcinoma, Targeting Stat1 and Stat3 to Reverse Radioresistance in Head and Neck Cancer, Targeting STAT3 for the Treatment of CDK4/6 Inhibitor Resistant Advanced Estrogen Receptor Positive Breast Cancer Patients
OpenAlex ID: W4302275712