您好,欢迎来到试剂仪器网! [登录] [免费注册]
试剂仪器网
位置:首页 > 产品库 > TIC10 Analogue
立即咨询
咨询类型:
     
*姓名:
*电话:
*单位:
Email:
*留言内容:
请详细说明您的需求。
*验证码:
 
TIC10 Analogue
本产品不向个人销售,仅用作科学研究,不用于任何人体实验及非科研性质的动物实验。
TIC10 Analogue图片
CAS NO:41276-02-2
规格:≥98%
包装与价格:
包装价格(元)
5mg电议
25mg电议
50mg电议
100mg电议
250mg电议
500mg电议

产品介绍
理化性质和储存条件
Molecular Weight (MW)386.49
FormulaC24H26N4O
CAS No.41276-02-2
Storage-20℃ for 3 years in powder form
-80℃ for 2 years in solvent
Solubility (In vitro)DMSO: 11 mg/mL (28.5 mM)
Water: <1 mg/mL
Ethanol: <1 mg/mL
Other infoSynonym: TIC10 isomer; TIC 10 isomer; TIC10 isomer; ONC201 isomer; ONC 201 isomer; ONC201 isomer.

InChi Key: RSAQARAFWMUYLL-UHFFFAOYSA-N

InChi Code: InChI=1S/C24H26N4O/c1-18-7-5-6-10-20(18)16-28-22-11-13-26(15-19-8-3-2-4-9-19)17-21(22)23(29)27-14-12-25-24(27)28/h2-10H,11-17H2,1H3

SMILES Code: O=C1C(CN(CC2=CC=CC=C2)CC3)=C3N(CC4=CC=CC=C4C)C5=NCCN15

Chemical Name7-benzyl-10-(2-methylbenzyl)-2,3,6,7,8,9-hexahydroimidazo[1,2-a]pyrido[4,3-d]pyrimidin-5(10H)-one
实验参考方法

In Vitro

Cell Assay: TIC10 causes a dose-dependent increase in TRAIL mRNA and induces TRAIL protein localization on the cell surface of several cancer cell lines in a p53-independent manner. TIC10 has broad-spectrum activity against multiple malignancies in vitro and induces an increase in sub-G1 DNA content suggestive of cell death in TRAIL-sensitive HCT116 p53–/– cells, but does not alter the cell cycle profiles of normal fibroblasts at equivalent doses. TIC10 decreases the clonogenic survival of cancer cell lines and spares normal fibroblasts. TIC10 increases the percentage of sub-G1 DNA in cancer cells in a p53-independent and Bax-dependent manner, as previously reported for TRAIL-mediated apoptosis. TIC10-induced TRAIL up-regulation is Foxo3a-dependent, which also up-regulates TRAIL death receptor DR5 among other targets, potentially allowing for sensitization of some TRAIL-resistant tumor cells. TIC10 inactivates kinases Akt and extracellular signal–regulated kinase (ERK), leading to the translocation of Foxo3a into the nucleus, where it binds to the TRAIL promoter to up-regulate gene transcription. TIC10 is an efficacious antitumor therapeutic agent that acts on tumor cells and their microenvironment to enhance the concentrations of the endogenous tumor suppressor TRAIL.

In Vivo

TIC10 and TRAIL treatment causes tumor regression in the HCT116 p53–/– xenograft to a comparable extent when both are administered as multiple doses. TIC10 also induces regression of MDA-MB-231 human triple-negative breast cancer xenografts, whereas TRAIL-treated tumors progressed. In DLD-1 colon cancer xenografts, TIC10 induces tumor stasis at 1 week after treatment, whereas TRAIL-treated tumors progresses after a single dose. A single dose of TIC10 also induces a sustained regression of the SW480 xenograft and is equally effective when delivered by intraperitoneal or oral route, suggesting favorable oral bioavailability for TIC10. TIC10 causes tumor-specific cell death by TRAIL-mediated direct and bystander effects. TIC10 is an effective antitumor agent against orthotopic human glioblastoma multiforme tumors.

Animal model

Female athymic nu/nu mice

Formulation & Dosage

Dissolved in DMSO; 25, 50, 100 mg/kg; i.p./p.o.

References

Sci Transl Med. 2013 Feb 6;5(171):171ra17.