CAS NO: | 603288-22-8 |
规格: | ≥98% |
包装 | 价格(元) |
5mg | 电议 |
25mg | 电议 |
50mg | 电议 |
100mg | 电议 |
250mg | 电议 |
500mg | 电议 |
Molecular Weight (MW) | 512.53 |
Formula | C28H25FN6O3 |
CAS No. | 603288-22-8 |
Storage | -20℃ for 3 years in powder form |
-80℃ for 2 years in solvent | |
Solubility (In vitro) | DMSO: 100 mg/mL (195.1 mM) |
Water: <1 mg/mL | |
Ethanol: 2 mg/mL warmed (3.9 mM) | |
SMILES | O=C(C(C1=CN2C3=C1C=C(F)C=C3CN(C(N4CCCCC4)=O)CC2)=C5C6=CN=C7C=CC=CN76)NC5=O |
Synonyms | LY 2090314; LY2090314; LY-2090314 Chemical Name: 3-(9-fluoro-2-(piperidine-1-carbonyl)-1,2,3,4-tetrahydro-[1,4]diazepino[6,7,1-hi]indol-7-yl)-4-(imidazo[1,2-a]pyridin-3-yl)-1H-pyrrole-2,5-dione InChi Key: HRJWTAWVFDCTGO-UHFFFAOYSA-N InChi Code: InChI=1S/C28H25FN6O3/c29-18-12-17-15-34(28(38)32-7-3-1-4-8-32)11-10-33-16-20(19(13-18)25(17)33)23-24(27(37)31-26(23)36)21-14-30-22-6-2-5-9-35(21)22/h2,5-6,9,12-14,16H,1,3-4,7-8,10-11,15H2,(H,31,36,37) |
In Vitro | In vitro activity: LY2090314 selectively inhibits the activity of GSK-3 by interrupting ATP binding. LY2090314 is able to stabilize β-catenin. LY2090314 shows limited efficacy as monotherapy. LY3090314 enhances the efficacy of cisplatin and carboplatin in solid tumor cancer cell lines in vitro.
Kinase Assay: LY2090314 is a potent inhibitor of glycogen synthase kinase-3 (GSK-3) with IC50 values of 1.5 nM and 0.9 nM for GSK-3α and GSK-3β, respectively.
Cell Assay: LY2090314 (20 nM) promotes a time-dependent stabilization of β-catenin total protein as well as an induction of Axin2. LY2090314 is highly selective towards GSK3 as demonstrated by its fold selectivity relative to a large panel of kinases. LY2090314 potently induces apoptotic cell death in a panel of melanoma cell lines irrespective of BRAF mutation status. Cell death induced by LY2090314 is dependent on β-catenin and GSK3β knockdown increases the sensitivity of cells to LY2090314. LY2090314 remains active in cell lines resistant to Vemurafenib and has an independent mechanism of action. |
In Vivo | LY2090314 enhances the efficacy of cisplatin and carboplatin in solid tumor cancer xenografts |
Animal model | Athymic nude mice:Five million A375 human melanoma cancer cells are injected S.C. in the flank of female 6 to 8 week old athymic nude mice in a 1:1 mixture with matrigel. Mice are monitored daily for palpable tumors. When tumors reach appr 100 mm2 mice are randomized into groups receiving either LY2090314 (25 mg/kg Q3D) or vehicle (20% Captisol/0.01N HCl) via i.v. administration. Tumor volume (measured by calipers) and animal body weight are recorded twice weekly. Tumor volumes are calculated using the formula: (a2 × b)/2 (a being the smaller and b being the larger dimension of the tumor). For combination studies with DTIC (60 mg/kg QD), LY2090314 is dosed at 2.5 mg/kg Q3D and tumor growth monitored. |
Formulation & Dosage | LY2090314 (25 mg/kg Q3D) or vehicle (dissolved in 20% Captisol/0.01N HCl) via i.v. administration. |
References | [1] Brail LH, et al. J Clin Oncol, 2011, 29, abstr 3030. |