Cell lines

a variety of cell lines

Preparation method

The solubility of this compound in DMSO is >26.5mg/mL. General tips for obtaining a higher concentration: Please warm the tube at 37℃ for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below -20℃ for several months.

Applications

In a variety of cell lines, CPI-169 inhibited the catalytic activity of PRC2 with IC50 value of< 1nM, decreased cellular levels of H3K27me3 with EC50 value of 70 nM, and triggered cell cycle arrest and apoptosis.

Animal models

EZH2 mutant KARPAS-422 diffuse large B-cell lymphoma (DLBCL) xenograft

Dosage form

200 mpk twice daily (BID); administered subcutaneously

Application

In EZH2 mutant KARPAS-422 diffuse large B-cell lymphoma (DLBCL) xenograft, CPI-169 is well tolerated in mice with no observed toxic effect or body weight loss. CPI-169 treatment led to tumor growth inhibition (TGI) in a dose-dependent way and reduced the pharmacodynamic marker H3K27me3. The highest dose (200 mpk BID) led to complete tumor regression.

Other notes

Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal.

CPI-169 is a novel, small molecule and potent inhibitor of enhancer of zeste homolog 2 (EZH2) with an IC50 value of<1nM for polycomb repressive complex 2 (PRC2) [1].

CPI-169 has been found to be a potent EZH2 inhibitor with an IC50 value of<1nM for polycomb repressive complex 2 (PRC2). In addition, CPI-169 has been reported to reduce cellular levels of histone H3 on lysine 27(H3K27) with an EC50 value of 70nM. Moreover, CPI-169 has been exhibited to trigger cell cycle arrest and apoptosis in cells. Apart from these, treatment the inhibitor at 200mpk twice daily, CPI-169 has been noted to have a well tolerated in mice with no observed toxic effect or body weight loss [1].

References:
[1] Vidya Balasubramanian, Priya Iyer, Shilpi Arora, Patrick Troyer, Emmanuel Normant. Constellation Pharmaceuticals, Cambridge, MA. CPI-169, a novel and potent EZH2 inhibitor, synergizes with CHOP in vivo and achieves complete regression in lymphoma xenograft models