Diptoindonesin G is a middle domain HSP90 modulator for cancer treatment

Diptoindonesin G, a new Hsp90 drug

“…In the recent JBC Editor’s Pick by Donahue et al . the authors discovered that diptoindonesin G (dip G), an anticancer drug, is a member of a new class of Hsp90 inhibitors ( 6 ). Dip G was initially thought to modulate the E3 ligase CHIP ( 7 ) and has been studied in ER-positive breast cancer, acute myeloid leukemia, triple negative breast cancer, and prostate cancer.…”

“…Dip G was initially thought to modulate the E3 ligase CHIP ( 7 ) and has been studied in ER-positive breast cancer, acute myeloid leukemia, triple negative breast cancer, and prostate cancer. However, the authors now show that, instead of modulating CHIP, dip G is a regulator of Hsp90 function ( 6 ). The authors used fluorescence polarization assays to show that a dip G analog, deoxy-dip G, bound Hsp90 with modest affinity (K d ∼ 0.3 μM).…”

“…Donahue et al . ( 6 ) moreover used RT-qPCR to assess the effect of Hsp90 modulators on the heat shock response in ER-positive cells and demonstrated that, unlike tanespimycin, dip G did not induce the expression of Hsps, including Hsp90, Hsp70, Hsp40, and Hsp27. These results suggest that dip G modulates protein expression in a manner distinct from N-terminal inhibitors.…”