Modulador de Interacção Proteína-Proteína

Potent inhibitor of the interaction between defective cullin neddylation protein DCN1 and NEDD8-conjugating enzyme UBC12 with IC50 of 11 nM. WS 383 blocks the DCN1-UBC12 interaction in a reversible manner, selectively inhibits Cul3/1 neddylation and induces accumulation of p21, p27, and NRF2 proteins.

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

Obatoclax mesylate is a synthetic small molecule, which is derived from chemical synthesis with a primary mode of action as a pan-BCL-2 inhibitor. This compound antagonizes multiple anti-apoptotic proteins within the BCL-2 family, ultimately promoting apoptosis in malignant cells. Its ability to inhibit these proteins disrupts the survival mechanisms that cancer cells exploit, potentially restoring apoptotic pathways that are often dysregulated in cancerous tissues.

(2R)-Arimoclomol maleate is an investigational pharmaceutical compound, which is an orally bioavailable small molecule with pharmacological activity primarily targeting cellular protein homeostasis mechanisms. This therapeutic agent is derived from molecular chaperones and operates by selectively enhancing the expression of heat shock proteins (HSPs). The mechanism of action involves the modulation of the heat shock response, wherein (2R)-Arimoclomol maleate amplifies the natural cellular defense pathways against protein misfolding and aggregation.

KRAS G12C inhibitor

Induces Kruppel like factor 4 (KLF4) and reduces the expression of MYC.  Anti-tumor activity of APTO 253 has been demonstrated in AML and haematological malignancies. Inducing KLP4 expression in ovarian cancer cells using APT0 253 sensitises cells to cisplatin  and paclitaxel. BRCA1/2-deficient cancer cells are hypersensitive to APTO 253, which mediates its action by causing DNA damage.

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.

Autophagy inhibitor that selectively targets the StART domain of GRAMD1A

Inhibitor of BET bromodomain; antineoplastic

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.

17-AAG is the first clinically tested hsp90 inhibitor that exhibits antitumor activity. Its antitumor effects are documented in vivo for various animal models, including erbB2-dependent breast cancer, prostate cancer models, and melanoma.

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.