product name TIC10 analog
Description: TIC10 Analogue is an analogue of TIC10, which inactivates Akt and ERK to induce TRAIL through Foxo3a, possesses superior drug properties: delivery across the blood-brain barrier, superior stability and improved pharmacokinetics. TIC10 isomer is an isomer and the “inactive version” of TIC10. TIC-10 isomer was introduced to the research community since it was structurally wrong-assigned as the bioactive TIC-10 during early stage development of TIC-10 (now called ONC-201). TIC-10 isomer was found to be inactive, which did not reduce the viability of cancer cells.
References: Sci Transl Med. 2013 Feb 6;5(171):171ra17.
386.49
Formula
C24H26N4O
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
Solubility (In vivo)
Chemical Name
7-benzyl-10-(2-methylbenzyl)-2,3,6,7,8,9-hexahydroimidazo[1,2-a]pyrido[4,3-d]pyrimidin-5(10H)-one
other peoduct :References PubMed ID：:http://www.ncbi.nlm.nih.gov/pubmed/19394393
| In Vitro | Kinase Assay:
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. |
Related Posts
product name TIC10 analog
Description: TIC10 Analogue is an analogue of TIC10, which inactivates Akt and ERK to induce TRAIL through Foxo3a, possesses superior drug properties: delivery across the blood-brain barrier, superior stability and improved pharmacokinetics. TIC10 isomer is an isomer and the “inactive version” of TIC10. TIC-10 isomer was introduced to the research community since it was structurally wrong-assigned as the bioactive TIC-10 during early stage development of TIC-10 (now called ONC-201). TIC-10 isomer was found to be inactive, which did not reduce the viability of cancer cells.
References: Sci Transl Med. 2013 Feb 6;5(171):171ra17.
386.49
Formula
C24H26N4O
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
Solubility (In vivo)
Chemical Name
7-benzyl-10-(2-methylbenzyl)-2,3,6,7,8,9-hexahydroimidazo[1,2-a]pyrido[4,3-d]pyrimidin-5(10H)-one
other peoduct :References PubMed ID：:http://www.ncbi.nlm.nih.gov/pubmed/19394393
| In Vitro | Kinase Assay:
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. |