TTI-101: A competitive inhibitor of STAT3 that spares oxidative phosphorylation and reverses mechanical allodynia in mouse models of neuropathic pain.

ABSTRACT: Signal Transducer and Activator of Transcription (STAT) 3 emerged rapidly as a high-value target for treatment of cancer. However, small-molecule STAT3 inhibitors have been slow to enter the clinic due, in part, to serious adverse events (SAE), including lactic acidosis and peripheral neuropathy, which have been attributed to inhibition of STAT3's mitochondrial function. Our group developed TTI-101, a competitive inhibitor of STAT3 that targets the receptor pY705-peptide binding site within the Src homology 2 (SH2) domain to block its recruitment and activation. TTI-101 has shown target engagement, no toxicity, and evidence of clinical benefit in a Phase I study in patients with solid tumors. Here we report that TTI-101 did not affect mitochondrial function, nor did it cause STAT3 aggregat

SUBMITTER: Kasembeli MM 

PROVIDER: S-EPMC8478865 | biostudies-literature | 2021 Oct

REPOSITORIES: biostudies-literature