dordaviprone (Modeyso, ONC201)

Indications

• used to treat diffuse midline glioma with a H3 K27M mutation

Pharmacokinetics

• crosses the blood-brain barrier
• plasma protein binding 95-97%
• metabolized by CYP3A4 with minor contribution from CYP2B6, CYP2C8, CYP2C9, CYP2D6, & CYP3A5
• metabolites eliminated in the urine (70%) & feces (20%)
  • no unchanged dordaviprone found in urine or feces
• mean terminal half-life is 11 hours (30%)
• apparent clearance is ~ 27 L/hr (48%)

Adverse effects

• prolongation of the QT interval

Drug interactions

• see ref

Mechanism of action

• activation of mitochondrial caseinolytic protease P (ClpP)
• antagonism of the dopamine D2 receptor & dopamine D3 receptor
• activation of Activating Transcription Factor 4 (ATF4)
• induction of endoplasmic reticulum (ER) stress response
• induces apoptosis

More general terms

• antineoplastic agent (chemotherapeutic agent)

Database

• PubChem: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=73777259
• PubChem: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=121596510