CDIM8

**CDIM8** is a synthetic small molecule, chemically described as 1,1-bis(3′-indolyl)-1-(p-hydroxyphenyl)methane, and serves as a prototypical ligand for the orphan nuclear receptor NR4A1 (Nur77). It functions as an **NR4A1 antagonist**, inhibiting NR4A1-dependent transactivation and mimicking the cellular effects of NR4A1 knockdown. Mechanistically, CDIM8 inactivates NR4A1-regulated pro-oncogenic pathways, leading to inhibited growth, survival, migration, and invasion of several cancer cell types, including breast cancer and rhabdomyosarcoma (RMS) cells. CDIM8 also downregulates cancer-related genes such as survivin, Bcl-2, EGFR, c-MET, mTOR, β-catenin, and fusion oncoprotein PAX3-FOX01. It blocks TGFβ-induced nuclear export of NR4A1, inhibits TGFβ-induced invasion, and induces tumor suppressor cytokine IL-24 via ROS signaling. In vivo, CDIM8 has demonstrated antitumor efficacy in mouse xenograft models at 20–40 mg/kg/day, but its potency is limited by rapid metabolic conjugation at the phenolic hydroxyl. The addition of ortho substituents on the phenyl ring (buttressed analogs) improves metabolic stability and antitumor potency[1][2][4].

Other names

DIM-C-pPhOH1,1-bis(3′-indolyl)-1-(p-hydroxyphenyl)methane