product name Spautin-1
Description: Spautin-1 is a novel, potent and specific autophagy inhibitor, and inhibits the deubiquitinating activity of USP10 and USP13 with IC50 of ∼0.6-0.7 μM. It also enhances IM-induced CML cell apoptosis by reducing the expression of the anti-apoptotic proteins Mcl-1 and Bcl-2 and enhances IM-induced apoptosis by inactivating PI3K/AKT and activating downstream GSK3β, which can lead to downregulation of Mcl-1 and Bcl-2. Spautin-1 represents a promising agent to improve the efficacy of IM in the treatment of patients with CML.
References: Cell. 2011 Sep 30;147(1):223-34; Biochem J. 2013 May 1;451(3):375-88.
271.26
Formula
C15H11F2N3
CAS No.
1262888-28-7
Storage
-20℃ for 3 years in powder form
-80℃ for 2 years in solvent
Solubility (In vitro)
DMSO: 54 mg/mL (199.1mM)
Water: < 1 mg/mL
Ethanol: 7 mg/mL (25.8 mM)
Solubility (In vivo)
Synonyms
other peoduct :References PubMed ID：:http://www.ncbi.nlm.nih.gov/pubmed/19396826
| In Vitro |
In vitro activity: In Bcap-37 cells, Spautin-1 dramatically enhanced cell death in glucose-free media and induces apoptotic morphology. In Bax-Bak DKO cells, spautin-1 inhibits etoposide induced autophagic cell death. Spautin-1 promots the degradation of Vps34 complexes by regulating the deubiquitination activity of USP10 and USP13, and reduces the levels of PtdIns3P. In PDGF-treated cells, spautin-1 stabilizes α-smooth muscle cell actin and calponin, prevents actin filament disorganization, diminishes production of extracellular matrix, and abrogates VSMC hyperproliferation and migration. In CML cells, spautin-1 markedly inhibits IM-induced autophagy by downregulating Beclin-1, and enhances IM-induced apoptosis by inactivating PI3K/AKT and activating downstream GSK3β. Spautin-1 also specifically reduces infectious dengue virus titers in BHK-21 cells. Kinase Assay: Cell Assay: Spautin-1 promotes the degradation of Vps34 PI3 kinase complexes via inhibiting two ubiquitinspecific peptidases, USP10 and USP13, that target the Beclin1 subunit of Vps34 complexes. Spautin-1 had no effect on the growth and survival of Bcap-37 cells under normal culture conditions but dramatically enhanced cell death in glucose-free media. Under glucose-free conditions, western blotting for LC3 further confirmed that autophagy was induced, which was inhibited by spautin-1. Similar results were obtained with MCF-7 and BT549 cells. Therefore, spautin-1 can sensitize tumor cells to apoptosis under nutritional deprived conditions. |
|---|---|
| In Vivo | |
| Animal model | |
| Formulation & Dosage | |
| References | Cell. 2011 Sep 30;147(1):223-34; Biochem J. 2013 May 1;451(3):375-88. |
Related Posts
product name Spautin-1
Description: Spautin-1 is a novel, potent and specific autophagy inhibitor, and inhibits the deubiquitinating activity of USP10 and USP13 with IC50 of ∼0.6-0.7 μM. It also enhances IM-induced CML cell apoptosis by reducing the expression of the anti-apoptotic proteins Mcl-1 and Bcl-2 and enhances IM-induced apoptosis by inactivating PI3K/AKT and activating downstream GSK3β, which can lead to downregulation of Mcl-1 and Bcl-2. Spautin-1 represents a promising agent to improve the efficacy of IM in the treatment of patients with CML.
References: Cell. 2011 Sep 30;147(1):223-34; Biochem J. 2013 May 1;451(3):375-88.
271.26
Formula
C15H11F2N3
CAS No.
1262888-28-7
Storage
-20℃ for 3 years in powder form
-80℃ for 2 years in solvent
Solubility (In vitro)
DMSO: 54 mg/mL (199.1mM)
Water: < 1 mg/mL
Ethanol: 7 mg/mL (25.8 mM)
Solubility (In vivo)
Synonyms
other peoduct :References PubMed ID：:http://www.ncbi.nlm.nih.gov/pubmed/19396826
| In Vitro |
In vitro activity: In Bcap-37 cells, Spautin-1 dramatically enhanced cell death in glucose-free media and induces apoptotic morphology. In Bax-Bak DKO cells, spautin-1 inhibits etoposide induced autophagic cell death. Spautin-1 promots the degradation of Vps34 complexes by regulating the deubiquitination activity of USP10 and USP13, and reduces the levels of PtdIns3P. In PDGF-treated cells, spautin-1 stabilizes α-smooth muscle cell actin and calponin, prevents actin filament disorganization, diminishes production of extracellular matrix, and abrogates VSMC hyperproliferation and migration. In CML cells, spautin-1 markedly inhibits IM-induced autophagy by downregulating Beclin-1, and enhances IM-induced apoptosis by inactivating PI3K/AKT and activating downstream GSK3β. Spautin-1 also specifically reduces infectious dengue virus titers in BHK-21 cells. Kinase Assay: Cell Assay: Spautin-1 promotes the degradation of Vps34 PI3 kinase complexes via inhibiting two ubiquitinspecific peptidases, USP10 and USP13, that target the Beclin1 subunit of Vps34 complexes. Spautin-1 had no effect on the growth and survival of Bcap-37 cells under normal culture conditions but dramatically enhanced cell death in glucose-free media. Under glucose-free conditions, western blotting for LC3 further confirmed that autophagy was induced, which was inhibited by spautin-1. Similar results were obtained with MCF-7 and BT549 cells. Therefore, spautin-1 can sensitize tumor cells to apoptosis under nutritional deprived conditions. |
|---|---|
| In Vivo | |
| Animal model | |
| Formulation & Dosage | |
| References | Cell. 2011 Sep 30;147(1):223-34; Biochem J. 2013 May 1;451(3):375-88. |