[CAS NO. 946518-60-1] LY2409881 trihydrochloride
PRODUCTS SPECIFICATIONS [946518-60-1]
DESCRIPTION [946518-60-1]
Overview
| MDL | MFCD28900676 |
|---|---|
| Molecular Weight | 594.43 |
| Molecular Formula | C24H32Cl4N6OS |
| SMILES | O=C(C1=C(C=C(C2=NC(NCCCN3CCN(C)CC3)=NC=C2Cl)S4)C4=CC=C1)NC5CC5.[H]Cl.[H]Cl.[H]Cl |
2 Publications Citing Use of MCE
Summary
LY2409881 trihydrochloride is a selective IκB kinase β ( IKK2 ) inhibitor with an IC 50 of 30 nM.
IC50 & Target
|
IKK2 30 nM (IC 50 ) |
In Vitro
LY2409881 is an IKK2 inhibitor that inhibits TNFα-induced activation of NF-κB. By in vitro kinase assay, LY2409881 potently inhibits IKK2, with an IC 50 of 30 nM. In contrast, the IC 50 for IKK1 and other common kinases is at least one log higher. The specificity of LY2409881 for NF-κB signaling is further studied in a cell-based assay, by examining the effect of LY2409881 in the TNFα-dependent antiapoptosis function. TNFα is a well-characterized upstream stimulus of NF-κB. In the ovarian cancer cell line SKOV3, LY2409881 demonstrates moderate cytotoxicity, whereas TNFα at 10 ng/mL does not cause any cytotoxicity. In contrast, coadministration of LY2409881 and TNFα results in markedly higher cell killing compared with LY2409881. This is because TNFα-dependent activation of antiapoptotic signals mediated by NF-κB is blocked by LY2409881, while the proapoptotic TNF receptor-associated death domain (TRADD) and FAS-associated death domain (FADD) cascade pathways activated by TNFα are not affected by LY2409881 [1] .
MCE has not independently confirmed the accuracy of these methods. They are for reference only.
In Vivo
A well-established xenograft model of DLBCL is used to confirm the activity of LY2409881 in vivo. SCID-beige mice implanted with LY10 cell-derived tumors are given intraperitoneal injections of LY2409881 twice weekly at three different doses: 50, 100, and 200 mg/kg. The treatments are well tolerated, resulting in no death or severe morbidity of the mice. The average tumor volume is graphed as a function of time for each treatment group. The rates of tumor volume growth of the treatment groups are all significantly slower than the untreated control group (P≤0.01) [1] .
MCE has not independently confirmed the accuracy of these methods. They are for reference only.
Appearance
Solid
Shipping
Room temperature in continental US; may vary elsewhere.
Storage
4°C, sealed storage, away from moisture
* In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture)
Solvent & Solubility
DMSO : 14.29 mg/mL ( 24.04 mM ; Need ultrasonic)
H 2 O : < 0.1 mg/mL (ultrasonic;warming;heat to 60°C) (insoluble)
Stock Solutions
| Concentration Solvent Mass | 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 |
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1.
Add each solvent one by one: 20% SBE-β-CD in saline
Solubility: 35 mg/mL (58.88 mM); Clear solution; Need ultrasonic
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2.
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3.
Add each solvent one by one: 10% DMSO >> 90% (20% SBE-β-CD in saline)
Solubility: ≥ 1.43 mg/mL (2.41 mM); Clear solution
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4.
Add each solvent one by one: 10% DMSO >> 90% corn oil
Solubility: ≥ 1.43 mg/mL (2.41 mM); Clear solution