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CC-115 Sale

目录号 : GC16654

A dual inhibitor of mTOR and DNA-PK

CC-115 Chemical Structure

Cas No.:1228013-15-7

规格 价格 库存 购买数量
10mM (in 1mL DMSO)
¥840.00
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5mg
¥725.00
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10mg
¥1,376.00
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25mg
¥3,087.00
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Sample solution is provided at 25 µL, 10mM.

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实验参考方法

Kinase experiment:

An HTR-FRET substrate phosphorylation assay is employed for mTOR kinase. PI3Kα IC50 determinations are outsourced using the mobility shift assay format. Compounds (e.g., CC-115) are assessed against concentrations of ATP at approximately the Km for the assay, with average ATP Km of 15 μM and 50 μM for the mTOR and PI3K assays, respectively[1].

Cell experiment:

PC-3 cells are cultured in growth media. For biomarker studies cells are treated for 1 h and then assayed for pS6 and pAkt levels using MesoScale technology. For proliferation experiments, cells are treated with compound (e.g., CC-115) and then allowed to grow for 72 h. All data are normalized and represented as a percentage of the DMSO-treated cells. Results are then expressed as IC50 values[1].

Animal experiment:

Mice[1]Encouraged by the observed exposures, CC-115 is advanced into single dose PK/PD studies assessing mTOR pathway biomarker inhibition in tumor bearing mice. PC-3 tumor-bearing mice are administered with a single dose of CC-115, dosed orally at either 1 or 10 mg/kg, and plasma and tumor samples are collected at various time points for analysis. Significant inhibition of both mTORC1 (pS6) and mTORC2 (pAktS473) is observed for all compounds and the level of biomarker inhibition correlated to plasma compound levels.

References:

[1]. 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.

产品描述

IC50: 21/ 13 nM for mTOR/DNA-PK

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].

Clinical trial: Clinical efficacy of CC-115 was studied in 8 patients with relapsed/refractory CLL/small lymphocytic lymphoma harboring ATM deletions/mutations. Results showed that all but one patient had a decrease in lymphadenopathy, leading to 1 IWCLL partial response (PR) and 3 PRs with lymphocytosis. These early promising clinical activity suggested that CC-115 might be developed further for treatment of CLL [1].

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.

Chemical Properties

Cas No. 1228013-15-7 SDF
化学名 1-ethyl-7-(2-methyl-6-(1H-1,2,4-triazol-3-yl)pyridin-3-yl)-3,5-dihydropyrazino[2,3-b]pyrazin-2(1H)-one
Canonical SMILES CCN1C(CN=C2C1=NC(C(C=CC(C3=NNC=N3)=N4)=C4C)=CN2)=O
分子式 C16H16N8O 分子量 336.35
溶解度 ≥ 50mg/mL in DMSO 储存条件 Store at -20°C
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储备液的保存方式和期限:-80°C 储存时,请在 6 个月内使用,-20°C 储存时,请在 1 个月内使用。
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溶解性数据

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1 mg 5 mg 10 mg
1 mM 2.9731 mL 14.8655 mL 29.7309 mL
5 mM 0.5946 mL 2.9731 mL 5.9462 mL
10 mM 0.2973 mL 1.4865 mL 2.9731 mL
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