CC-115 Chemical Properties

Boiling point:

587.3±60.0 °C(Predicted)

Density 

1.56±0.1 g/cm3(Predicted)

storage temp. 

Store at -20°C

solubility 

≥50 mg/mL in DMSO; insoluble in EtOH; insoluble in H2O

form 

solid

pka

5.94±0.20(Predicted)

color 

Pink to red

CC-115 Usage And Synthesis

Uses

CC-115 is a potent and dual DNA-PK and mTOR kinase inhibitor with IC50s of 13 nM and 21 nM, respectively. CC-115 blocks both mTORC1 and mTORC2 signaling.

Biological Activity

cc-115 is a inhibitor of mtor/dna-pk.the mammalian target of rapamycin (mtor) kinase is a key mediator of the phosphoinositide 3-kinase /protein kinase b (akt pathway). the dna-dependent protein kinase (dna-pk) is a critical component of the dna repair machinery governings the response to dna damage, which serves to maintain genome integrity.

in vitro

previous study found that the proliferation induced by cd40(+) interleukin-21 stimulation could be completely blocked by cc-115, and cd40-mediated resistance to fludarabine and venetoclax could also be reverted by cc-115. moreover, bcr-mediated signaling was blocked by cc-115 and in cll samples from patients with acquired resistance to idelalisib treatment [1].

in vivo

preclinical studies showed that cc-115 had good in vivo pk profiles across multiple species with 53%, 76%, and around100% oral bioavailability in mouse, rat, and dog, respectively [2].

target

IC 50

21/ 13 nm for mtor/dna-pk

References

[1] thijssen r,et al. dual tork/dna-pk inhibition blocks critical signaling pathways in chronic lymphocytic leukemia. blood.2016 jul 28;128(4):574-83.
[2] mortensen ds, et al. optimization of a series of triazole containing mammalian target of rapamycin (mtor) kinase inhibitors and the discovery of cc-115. j med chem. 2015 jul 23;58(14):5599-5608.