Background:

PTC-209 HBr is the hydrobromide salt of PTC-209, a potent and selective BMI-1 inhibitor (IC50 = 0.5μM). It irreversibly impairs the colorectal tumor growth. [1]
BMI-1 is a component of polycomb repressive complex 1 (PRC1) and act as an epigenetic chromatin modifier for a variety of genes. [1]
PTC-209 inhibited both UTR-mediated reporter expression and endogenous BMI-1 expression in HCT116 (human colorectal cell) and HT1080 (human fibrosarcoma tumor cell) in a dose dependent manner. In addition, the inhibitory effect of PTC-209 was not from its cytotoxicity. PTC-209 also specifically reduced PRC1 activity. [1]
Viable colorectal cancer cell samples treated with PTC-209 ex vivo were injected back to the recipient mice in vivo, the mice exhibited reduced or no tumor growth comparing with the control groups. Thus PTC-209 irreversibly impaired colorectal cancer-initiating cells. Furthermore, in contrast with the control groups, tumor volume was significantly reduced in the colorectal tumor cell transplanted mice following PTC-209 administration. [1]
参考文献:
[1] Kreso A, van Galen P, Pedley NM, Lima-Fernandes E, Frelin C, Davis T, Cao L,Baiazitov R, Du W, Sydorenko N, Moon YC, Gibson L, Wang Y, Leung C, Iscove NN,Arrowsmith CH, Szentgyorgyi E, Gallinger S, Dick JE, O'Brien CA. Self-renewal as a therapeutic target in human colorectal cancer. Nat Med. 2014 Jan;20(1):29-36.