PBIT

IC50: 6, 3, 4.9, and 28 μM for JARID1A, JARID1B, JARID1C, and JARID1D, respectively

PBIT is a JARID1 family demethylases inhibitor.

JARID1B (also known as KDM5B or PLU1), a member of the JARID1 family of histone lysine demethylases, is identified for the demethylation of trimethylated lysine 27 in histone H3 that is a mark for actively transcribed genes. JARID1B is overexpressed in several cancers, such as prostate cancer, breast cancer, and lung cancer. Additionally, JARID1B is reported for mammary tumor formation in syngeneic or xenograft mouse models and JARID1B-expressing melanoma cells are related with increased self-renewal character.

In vitro: In previous study, PBIT was identified as JmjC histone demethylase inhibitor, which inhibited JARID1B with an in vitro IC50 of about 3 μM. Consistent with its inhibitory effect on JARID1B, PBIT treatment was able to inhibit the removal of H3K4me3 by JARID1B in cells. In addition, PBIT could inhibit the proliferation of cells expressing higher levels of JARID1B. These results suggested that PBIT could be regarded as a lead compound that could be further optimized for cancer therapy [1].

In vivo: Currently, there is no animal in vivo data reported.

Clinical trial: So far, no clinical study has been conducted.

Reference:
[1] J.  Sayegh, J. Cao, M. R. Zou, et al. Identification of small molecule inhibitors of Jumonji AT-rich interactive domain 1B (JARID1B) histone demethylase by a sensitive high throughput screen. The Journal of Biological Chemisty 288(13), 9408-9417 (2013).