DRUGGING "UNDRUGGABLE" DISEASE-CAUSING PROTEINS: FOCUS ON SIGNAL TRANSDUCER AND ACTIVATOR OF TRANSCRIPTION (STAT) 3.
Trans Am Clin Climatol Assoc
; 132: 61-76, 2022.
Article
en En
| MEDLINE
| ID: mdl-36196170
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.
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MEDLINE
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Sulfonamidas
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Humans
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En
Revista:
Trans Am Clin Climatol Assoc
Año:
2022
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Article