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Purity: ≥98%
LY2090314 (LY-2090314) is a novel and potent GSK-3 (glycogen synthase kinase-3) inhibitor for GSK-3α/β with potential antitumor activity. With an IC50 of 1.5 nM/0.9 nM, it inhibits GSK-3α/β. The antitumor effectiveness of chemotherapy regimens based on platinum may also be enhanced by LY2090314.
| Targets |
GSK-3β (IC50 = 0.9 nM); PI3Kγ (IC50 = 282 nM)
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| ln Vitro |
LY2090314 selectively inhibits the activity of GSK-3 by interrupting ATP binding. LY2090314 has the ability to keep β-catenin stable. As a monotherapy, LY2090314 exhibits a limited efficacy. Cisplatin and carboplatin are more effective in vitro against solid tumor cancer cell lines when combined with LY3090314. [1]
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| ln Vivo |
LY2090314 improves the effectiveness of cisplatin and carboplatin in solid tumor cancer xenografts. [1]
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| Cell Assay |
Cells were treated with various concentrations of drug for 5 h.
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| Animal Protocol |
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. Tumors that can be felt are checked for daily in mice. When tumors are approximately 100 mm2 in size, mice are divided into groups and given LY2090314 (25 mg/kg Q3D) or a vehicle (20% Captisol/0.01N HCl) intravenously. Animal body weight and tumor volume (calculated using calipers) are recorded twice weekly. The formula used to determine tumor volumes is (a2 b)/2, where a represents the tumor's smaller dimension and b its larger dimension. LY2090314 is dosed at 2.5 mg/kg Q3D for combination studies with DTIC (60 mg/kg QD), and tumor growth is tracked.
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| References |
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| Molecular Formula |
C28H25FN6O3
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|---|---|
| Molecular Weight |
512.5349
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| Exact Mass |
512.19722
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| Elemental Analysis |
C, 65.61; H, 4.92; F, 3.71; N, 16.40; O, 9.36
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| CAS # |
603288-22-8
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| Related CAS # |
603288-22-8
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| Appearance |
Off-white to light yellow solid powder
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| SMILES |
C1CCN(CC1)C(=O)N2CCN3C=C(C4=CC(=CC(=C43)C2)F)C5=C(C(=O)NC5=O)C6=CN=C7N6C=CC=C7
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| InChi Key |
HRJWTAWVFDCTGO-UHFFFAOYSA-N
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| 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)
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| Chemical Name |
3-[6-fluoro-10-(piperidine-1-carbonyl)-1,10-diazatricyclo[6.4.1.04,13]trideca-2,4,6,8(13)-tetraen-3-yl]-4-imidazo[1,2-a]pyridin-3-ylpyrrole-2,5-dione
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| Synonyms |
LY 2090314; LY2090314; LY-2090314
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO: ~100 mg/mL (~195.1 mM)
Water: <1 mg/mL Ethanol: ~2 mg/mL warmed (~3.9 mM) |
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| Solubility (In Vivo) |
5% DMSO+45% PEG 300+ddH2O: 17mg/mL (Please use freshly prepared in vivo formulations for optimal results.)
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| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.9511 mL | 9.7555 mL | 19.5111 mL | |
| 5 mM | 0.3902 mL | 1.9511 mL | 3.9022 mL | |
| 10 mM | 0.1951 mL | 0.9756 mL | 1.9511 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
| NCT Number | Status | Interventions | Conditions | Sponsor/Collaborators | Start Date | Phases |
| NCT01287520 | Completed | Drug: LY2090314 Drug: pemetrexed |
Advanced Cancer | Eli Lilly and Company | November 2007 | Phase 1 |
| NCT01214603 | Completed | Drug: LY2090314 | Leukemia | Eli Lilly and Company | November 2010 | Phase 2 |
LY2090314 is a GSK inhibitor which elevated Wnt signaling in melanoma cell lines. |
LY2090314 potently induces apoptotic cell death in a range 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.A. Melanoma cells stably transfected with shRNAs targeting β-catenin display decreased β-catenin and Axin2 protein expression by western blot. A375 (B) and M14 (C) cells expressing shRNAs targeting β-catenin (● Control; ■ β-catenin shRNA 1;▲β-catenin shRNA 2; ▼ β-catenin shRNA 3) become resistant to LY2090314 suggesting that β-catenin is required for apoptotic cell death in response to LY2090314.D, E.A375 cells targeted with GSK3β shRNA, but not GSK3α shRNA, demonstrates increased sensitivity to LY2090314 (4.5nM, 72hr).PLoS One.2015 Apr 27;10(4):e0125028. |
LY2090314 demonstrates activity in cell lines resistant to the BRAF inhibitor Vemurafenib and has an independent mechanism of action.PLoS One.2015 Apr 27;10(4):e0125028. |
LY2090314 elevates Axin2 gene expression in vivo, demonstrates single agent activity in the A375 xenograft model of melanoma and enhances the efficacy of DTIC.PLoS One.2015 Apr 27;10(4):e0125028. |
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