CC-115

本公司产品仅用于科研实验，不得用于人体或动物的临床与诊断

一种新型 mTOR 和 DNA-PK 双重抑制剂，IC50 分别为 21 nM 和 13 nM。

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.

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).

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.

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PI3K/Akt/mTOR signaling

mTOR

DNA-PK|mTOR|PI3Kα

Cancer

Blood cancer

1228013-15-7

336.3512

C16H16N8O

>98% (HPLC)

DMSO: ≥ 32 mg/mL

CCN1C(=O)CNC2=NC=C(N=C21)C3=C(N=C(C=C3)C4=NC=NN4)C

Pyrazino[2,3-b]pyrazin-2(1H)-one, 1-ethyl-3,4-dihydro-7-[2-methyl-6-(1H-1,2,4-triazol-5-yl)-3-pyridinyl]-

(-20℃)

With Ice Pack

≥ 2 years