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
| Target | Value |
DNA-PK
(Cell-free assay) | 0.013 μM |
mTOR
(Cell-free assay) | 0.021 μM |
PI3Kα
(Cell-free assay) | 0.852 μM |
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.
