CC-115

产品说明书

Print
Chemical Structure| 1228013-15-7 同义名 : -
CAS号 : 1228013-15-7
货号 : A642364
分子式 : C16H16N8O
纯度 : 98+%
分子量 : 336.35
MDL号 : MFCD29036965
存储条件：

Pure form Inert atmosphere, 2-8°C

In solvent -20°C:3-6个月-80°C:12个月
溶解度 : -
动物实验配方：
生物活性
靶点

  • DNA-PK

    DNA-PK, IC50:0.013 μM

  • DNA-PK

    DNA-PK, IC50:0.013 μM
描述 CC-115 is a dual inhibitor of mammalian target of rapamycin kinase (mTOR) and DNA-dependent protein kinase (DNA-PK), two members in the PI3K family. It inhibits TORK and DNA-PK with IC50 values of 0.021 and 0.013 µM, respectively[3]. In primary chronic lymphocytic leukemia (CLL) cells, CC-115 at 0.1-0.35 µM dose-dependently suppressed Ser-2056 phosphorylation on DNA-PK and bleomycin-induced Ser-1981 phosphorylation on ATM. CC-115 at 1 µM significantly inhibited irradiation (5 Gy)-induced γH2AX level in ATM/11q mutated CLL cells. Low dose CC-115 (0.35 µM) successfully blocked the constitutive phosphorylation of S6, a marker for mTORC1 activity, in all CLL cells. It also completely inhibited the phosphorylation of the mTORC1 and mTORC1 targets in BCR-stimulated CLL cells at the concentration of 1 µM. CC-115 induced caspase-dependent cell death in resting CLL cells with an IC50 value of 0.51 µM. CC-115 at the dose of 1 µM reverted CD40-mediated resistance to chemotherapy or venetoclax in CLL cells cultured on CD40L-expressing fibroblasts. CC-115 treatment (1 µM) also efficiently inhibited the proliferation of CLL cells[4]. In PC-3 tumor-bearing mice, administration of CC-115 at 0.25, 0.5 and 1 mg/kg twice daily or 1 mg/kg once daily resulted in the tumor volume reduction of 46%, 57%, 66% and 57%, respectively.
作用机制 CC-115 inhibits both mTOR and DNA-PK by extending the 7-substituent into the kinase catalytic pocket to inhibit their activities.
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

2.97mL

0.59mL

0.30mL

14.87mL

2.97mL

1.49mL

29.73mL

5.95mL

2.97mL
参考文献

[1]Thijssen R, Ter Burg J, 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, Perrin-Ninkovic SM, 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):5599-608.

[3]Mortensen DS, Perrin-Ninkovic SM, Shevlin G, Elsner J, Zhao J, Whitefield B, Tehrani L, Sapienza J, Riggs JR, Parnes JS, Papa P, Packard G, Lee BG, Harris R, Correa M, Bahmanyar S, Richardson SJ, Peng SX, Leisten J, Khambatta G, Hickman M, Gamez JC, Bisonette RR, Apuy J, Cathers BE, Canan SS, Moghaddam MF, Raymon HK, Worland P, Narla RK, Fultz KE, Sankar S. 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):5599-608. doi: 10.1021/acs.jmedchem.5b00627. Epub 2015 Jul 8. PMID: 26102506.

[4]Thijssen R, Ter Burg J, Garrick B, van Bochove GG, Brown JR, Fernandes SM, Rodríguez MS, Michot JM, Hallek M, Eichhorst B, Reinhardt HC, Bendell J, Derks IA, van Kampen RJ, Hege K, Kersten MJ, Trowe T, Filvaroff EH, Eldering E, Kater AP. Dual TORK/DNA-PK inhibition blocks critical signaling pathways in chronic lymphocytic leukemia. Blood. 2016 Jul 28;128(4):574-83. doi: 10.1182/blood-2016-02-700328. Epub 2016 May 27. PMID: 27235137.