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Purity: ≥98%
LY2409881 trihydrochloride (LY-2409881; LY 2409881), the trihydrochloride salt of LY-2409881, is a novel, potent and selective IKK2 ( IκB kinase β) inhibitor with potential anticancer and anti-inflammatory activity. It exhibits >10-fold selectivity for inhibiting IKK2 over IKK1 and other closely related kinases, with an IC50 of 30 nM for IKK2 (IκB kinase β). In vivo tumor growth in a SCID-beige xenograft mouse model was markedly reduced by LY2409881. Through the suppression of NF-κB, LY2409881 effectively complements histone deacetylase inhibitors in preclinical lymphoma models. In addition to causing concentration- and time-dependent growth inhibition and apoptosis in lymphoma cells, LY2409881 inhibited constitutively activated NF-κB. In lymphoma cells treated with the HDAC inhibitor romidepsin, LY2409881 reduced the activity of the NF-κB subunit p65, suggesting this may be the mechanism underlying the strong synergy seen between these two medications.
| Targets |
IKK2 (IC50 = 30 nM)
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| ln Vitro |
In diffuse large B-cell lymphoma (DLBCL) cells, LY2409881 inhibits constitutively activated NF-B and results in concentration- and time-dependent growth inhibition and apoptosis. LY2409881 exhibits a moderate level of cytotoxicity in the ovarian cancer cell line SKOV3. In SUDHL2 cells, LY2409881 inhibits cell growth synergistically with doxorubicin and cyclophosphamide, but not in LY1 cells. In order to stop the growth of SUDHL2 and LY1 cells, LY2409881 works in conjunction with the HDAC inhibitor romidepsin. [1]
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| ln Vivo |
LY2409881 (50, 100, and 200 mg/kg, i.p.) significantly slows the growth of the tumor in the SCID-beige xenograft mouse model.[1]
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| Enzyme Assay |
LY2409881 is an IKK2 inhibitor that inhibits TNFα-induced activation of NF-κB. LY2409881 has an IC50 of 30 nM in an in vitro kinase assay and potently inhibits IKK2. The IC50 for IKK1 and other popular kinases, however, is at least one log higher. By examining LY2409881's impact on the TNF-dependent antiapoptosis function, the specificity of the drug for NF-κB signaling is further investigated in a cell-based assay. An upstream stimulus of NF-κB with good characterization is TNFα .
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| Cell Assay |
In accordance with the instructions provided by the manufacturer, cytotoxicity is assessed using the CellTiter-Glo Reagent. Each treatment is performed in triplicate during the experiment in 96-well plates. Samples are typically collected 24, 48, and 72 hours after treatment. The percentage of living cells that declines with each treatment compared to the untreated control in the same experiment is a measure of cytotoxicity. The CalcuSyn Version 2.0 software is used to determine the IC50 for every cell line.
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| Animal Protocol |
Mice: There are mouse experiments. 107 Ly10 cells mixed with Matrigel are subcutaneously injected into five- to seven-week-old SCID beige mice in the posterior flank. The mice are divided into four groups of eight when the tumors reach 150 mm3: (1) the control group, which receives 5% dextrose in water; (2) the LY2409881 50 mg/kg in D5W; (3) the LY2409881 100 mg/kg in D5W; and (4) the LY2409881 200 mg/kg in D5W. For four weeks, LY2409881 or D5W is given intraperitoneally on days 1 and 4. The information is presented as the average tumor volume (mm3) for each group over time. The tumor volume is determined.
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| References |
| Molecular Formula |
C24H32CL4N6OS
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|---|---|
| Molecular Weight |
594.43
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| Exact Mass |
592.11
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| Elemental Analysis |
C, 48.49; H, 5.43; Cl, 23.86; N, 14.14; O, 2.69; S, 5.39
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| CAS # |
946518-60-1
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| Related CAS # |
LY2409881;946518-61-2
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| Appearance |
Solid powder
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| SMILES |
CN1CCN(CC1)CCCNC2=NC=C(C(=N2)C3=CC4=C(C=CC=C4S3)C(=O)NC5CC5)Cl.Cl.Cl.Cl
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| InChi Key |
IEXCRLAGBWKVPW-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C24H29ClN6OS.3ClH/c1-30-10-12-31(13-11-30)9-3-8-26-24-27-15-19(25)22(29-24)21-14-18-17(4-2-5-20(18)33-21)23(32)28-16-6-7-16;;;/h2,4-5,14-16H,3,6-13H2,1H3,(H,28,32)(H,26,27,29);3*1H
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| Chemical Name |
2-[5-chloro-2-[3-(4-methylpiperazin-1-yl)propylamino]pyrimidin-4-yl]-N-cyclopropyl-1-benzothiophene-4-carboxamide;trihydrochloride
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| Synonyms |
LY2409881 tri-HCl; LY2409881 trihydrochloride; LY-2409881; LY 2409881
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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) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 1.43 mg/mL (2.41 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 14.3 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 1.43 mg/mL (2.41 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 14.3 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 1.43 mg/mL (2.41 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. Solubility in Formulation 4: 2% DMSO+30% PEG 300+5% Tween 80+ddH2O: 5mg/mL Solubility in Formulation 5: 35 mg/mL (58.88 mM) in 20% SBE-β-CD in Saline (add these co-solvents sequentially from left to right, and one by one), clear solution; with ultrasonication. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.6823 mL | 8.4114 mL | 16.8228 mL | |
| 5 mM | 0.3365 mL | 1.6823 mL | 3.3646 mL | |
| 10 mM | 0.1682 mL | 0.8411 mL | 1.6823 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.
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