Page 88 - I. Chemical biology and drug discovery

[I. Chemical biology and drug discovery-51]

A rhenium isonitrile complex induces HSP60-mediated

mitochondrial apoptosis.

Junhyeong Yim¹, Seung Bum Park¹

¹Biophysics and Chemical Biology, Seoul National University, Seoul 08826, Korea

Many inorganic compounds, like Platin derivatives, are used to treat cancer. Interestingly, Rhenium based compounds
also showed anti-cancer effect. But unlike Platinum based compounds like Cisplatin or Carboplatin, which are DNA
crosslinkers, the mechanism that how Rhenium based compounds showed anti-cancer effect is still unclear. So We

are going to reveal and validate target protein of Rhenium Isonitrile Complex (TRIP), and to clarify the Mechanism

of Action (MoA) of TRIP against cancer cells via our novel target ID method, label-Free Target Identification Using
In-Gel Fluorescence Difference via Thermal Stability Shift, called TS-FITGE. TS-FITGE revealed target protein of TRIP
as HSP60, which works as chaperonin. Inhibit HSP60 by TRIP induces accumulation of misfolded proteins at

mitochondria. Misfolded proteins activate CHOP via JNK2/p-JNK2 pathway. CHOP activation may induce
mitochondrial apoptosis of cancer cells.