Dordaviprone

Boiling point: 559.7±60℃

Storage temp: Sealed in dry,Store in freezer, under -20°C

Solubility: Soluble in DMSO (up to 25 mg/ml at elevated temperatures)

Form: Solid

Color: Pale Yellow

Stability: Solutions in DMSO are stable for 2 months when stored at -20°C

Dordaviprone is a drug with anti-tumour activity: It exhibited anti-tumour activity in cell-based assays and in vivo models of H3 K27M-mutant diffuse glioma. Dordaviprone causes a concentration-dependent QTc interval prolongation. At 1.2 times the maximum recommended dose, the estimated mean QTcF change was 11.8 msec (90% CI: 9.8, 13.7). The exposure-response relationship and time course of pharmacodynamic response for the safety and effectiveness of dordaviprone have not been fully characterized.

Dordaviprone is a protease activator of the mitochondrial caseinolytic protease P (ClpP), a mitochondrial serine protease. Diffuse midline gliomas harboring an H3 K27M mutation are associated with the loss of H3 K27 trimethylation. In vitro, dordaviprone induced apoptosis and altered mitochondrial metabolism leading to restored histone H3 K27 trimethylation in H3 K27M-mutant diffuse glioma models. Dordaviprone activates ATF4 and induces endoplasmic reticulum (ER) stress response or integrated stress response (ISR). Dordaviprone also inhibits the dopamine D2 receptor, which are often overexpressed in multiple cancers, including glioblastoma.