Modulateur d'interaction protéine-protéine

Inhibits anti-apoptotic proteins Bcl-2, Bcl-xl and Bcl-w. Synergistic with chemotherapy and radiotherapy in several tumour cell lines. Potent activity as a single agent in lymphoid cancer and small cell lung cancer (SCLC) cell lines. Causes tumour regression in SCLC xenograft tumour in vivo.

Activator of RET signalling cascade and a derivative of a GFL mimetic compound BT 13. Molecular docking calculations and molecular dynamics simulations were performed in GDNF−GFRα1−RetA complex and showed that BT 18 binds to the allosteric site in GFRα1 as well as RetA surface interfacing GFRα1.

Reversible inhibitor of RGS proteins

A potent inhibitor of Wnt/β-catenin signalling pathway that interferes with β-catenin/TFC4 interaction. Reduces growth and motility of colon cancer cells. Inhibits self-renewal, whilst inducing differentiation in cancer stem cells.

Microtubule disrupter; anti-mitotic drug; anti-cancer alkaloid

A chemical probe for the dual bromodomains of human transcription-initiation-factor TFIID subunit 1 (TAF1). GNE 371 binds TAF1 with an IC50 of 10 nM and is selective over other bromodomain family members. Exerts anti-proliferative effects in synergy with BET inhibitor JQ1.

Inhibitor of clathrin-mediated endocytosis (CME) and ligand to the clathrin heavy chain (CHC). ES9-17 is an inhibitor of the CHC function with EC50 of 13 μM in plant model Arabidopsis thaliana. ES9-17 is a non-protonophoric CME inhibitor and it does not alter the cytoplasmic pH levels substantially. In a mammalian cell line HeLa, ES9-17 reduced the uptake of transferrin, which is a CME-driven process.

Potent and selective inhibitor of polycomb repressive complex 2 (PRC2), by binding to the K27me3-pocket of the regulatory EED subunit. Inhibits H3K27 methylation in histone 3. Has anti-tumor activity in murine xenograft models. Synergistic with EZH2 inhibitor against cancer cell growth.