CC-115

SKU: orb1226738

Description

A novel dual inhibitor of mTOR and DNA-PK with IC50 of 21 nM and 13 nM, respectively; blocks both mTORC1(pS6) and mTORC2(pAktS473) signaling in PC-3 cancer cells, in vitro and in vivo; exhibits dose-dependent efficacy in tumor xenograft models.Blood Cancer Phase 1 Clinical(In Vitro):CC-115 inhibits PC-3 cells proliferation with an IC50 of 138 nM. In a kinase selectivity assessment against a panel of 250 protein kinases at 3 μM, only one kinase other than mTOR kinase is identified with more than 50% inhibition (cFMS 57%, IC50=2.0 μM). Of the PI3K related kinases (PIKKs) tested, CC-115 proves to be equipotent against DNA PK (IC50=15 nM) and demonstrates 40 to >1000 fold selectivity against the remaining PIKKs tested; PI3K-alpha (IC50=0.85 μM), ATR (50% inhibition at 30 μM) and ATM (IC50>30 μM). The IC50 values for CC-115 are >10 μM against a panel of CYP enzymes and >33 μM for the hERG (human ether-a-go-go-related gene) ion channel. When screened in a single point assay at 10 μM against a Cerep receptor and enzyme panel only one target is inhibited >50% (PDE3, IC50=0.63 μM).(In Vivo):CC-115 shows good in vivo PK profiles across multiple species with 53%, 76% and ~100% oral bioavailability in mouse, rat and dog, respectively. CC-115 is tested at lower doses of 0.25, 0.5 and 1 mg/kg bid or 1 mg/kg qd, with observed corresponding tumor volume reductions of 46%, 57%, 66% and 57% respectively. CC-115 sustains inhibition though 24 hours. At the 1 mg/kg dose CC-115 shows significant inhibition at 1 and 3 hours, CC-115 demonstrating inhibition through 10 hours. CC-115 is evaluated using both once (qd) and twice (bid) daily dosing schedules.

Key Properties

• CAS Number: 1228013-15-7
• MW: 336.3512
• Purity: >98% (HPLC)
• Formula: C₁₆H₁₆N₈O
• SMILES: CCN1C(=O)CNC2=NC=C(N=C21)C3=C(N=C(C=C3)C4=NC=NN4)C
• Target: mTOR
• Solubility: DMSO: ≥ 32 mg/mL

Bioactivity

• In Vivo:
  CC-115 shows good In vivo PK profiles across multiple species with 53%, 76% and ~100% oral bioavailability in mouse, rat and dog, respectively. CC-115 is tested at lower doses of 0.25, 0.5 and 1 mg/kg bid or 1 mg/kg qd, with observed corresponding tumor volume reductions of 46%, 57%, 66% and 57% respectively. CC-115 sustains inhibition though 24 hours. At the 1 mg/kg dose CC-115 shows significant inhibition at 1 and 3 hours, CC-115 demonstrating inhibition through 10 hours. CC-115 is evaluated using both once (qd) and twice (bid) daily dosing schedules.
• In Vitro:
  CC-115 inhibits PC-3 cells proliferation with an IC50 of 138 nM. In a kinase selectivity assessment against a panel of 250 protein kinases at 3 μM, only one kinase other than mTOR kinase is identified with more than 50% inhibition (cFMS 57%, IC50 = 2.0 μM). Of the PI3K related kinases (PIKKs) tested, CC-115 proves to be equipotent against DNA PK (IC50 = 15 nM) and demonstrates 40 to >1000 fold selectivity against the remaining PIKKs tested; PI3K-alpha (IC50 = 0.85 μM), ATR (50% inhibition at 30 μM) and ATM (IC50>30 μM). The IC50 values for CC-115 are >10 μM against a panel of CYP enzymes and >33 μM for the hERG (human ether-a-go-go-related gene) ion channel. When screened in a single point assay at 10 μM against a Cerep receptor and enzyme panel only one target is inhibited > 50% (PDE3, IC50 = 0.63 μM).

Storage & Handling

• Storage: Storage temperature: -20°C. Stability: ≥ 2 years
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Quick Database Links

Gene Symbol

mTOR