[CAS NO. 431898-65-6] PS-1145
PRODUCTS SPECIFICATIONS [431898-65-6]
DESCRIPTION [431898-65-6]
Overview
| MDL | MFCD18089825 |
|---|---|
| Molecular Weight | 322.75 |
| Molecular Formula | C17H11ClN4O |
| SMILES | O=C(C1=CC=CN=C1)NC2=CC(Cl)=CC3=C2NC4=C3C=CN=C4 |
2 Publications Citing Use of MCE
Summary
PS-1145 is an IκB kinase ( IKK ) inhibitor with an IC 50 of 88 nM.
IC50 & Target
|
IKK 88 nM (IC 50 ) |
In Vitro
PS-1145 blocks TNFα-induced NF-κB activation in a dose- and time-dependent fashion in MM cells through inhibition of IκBα phosphorylation. Dexamethasone (Dex), which up-regulates IκBα protein, enhances blockade of NF-κB activation by PS-1145. PS-1145 blocks the protective effect of IL-6 against Dex-induced apotosis. TNFα-induced intracellular adhesion molecule (ICAM)-1 expression on both RPMI8226 and MM.1S cells is also inhibited by PS-1145. Moreover, PS-1145 inhibits both IL-6 secretion from bone marrow stromal cells (BMSCs) triggered by MM cell adhesion and proliferation of MM cells adherent to BMSCs [1] .
MCE has not independently confirmed the accuracy of these methods. They are for reference only.
In Vivo
Administration of either Bortezomib or PS-1145 (50 mg/kg) results in a significant decrease in serum levels of all 3 cytokines that is nonsignificantly different from those in mice that underwent transplantation with TCD BM alone [2] . PS1145 is injected intracerebroventricular (icv) as a pretreatment to block hypothalamic inflammation induced by IL-4 in adult male Wistar rats consuming a high-fat diet (HFD) over an 11-day period. The four groups of rats according to icv pretreatment/treatment condition are Veh/Veh, Veh/IL-4, PS1145/Veh, and PS1145/IL-4. Rats in the Veh/IL-4 group display increased weight gain on the HFD compared with the Veh/Veh group (P<0.05 on days 6-9). Importantly, the effect of icv IL-4 administration to increase body fat mass during high-fat (HF) feeding is completely blocked by icv PS1145 pretreatment at a dose that has no independent effect on body composition (on day 8: P<0.001, PS1145/Veh vs. PS1145/IL-4; P=not significant, PS1145/Veh vs. Veh/Veh). In PS1145/IL-4 injected rats, IL-1β mRNA content is decreased by ~75% compared with that of Veh/IL-4-injected rats [3] .
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
| Powder | -20°C | 3 years |
|---|---|---|
| 4°C | 2 years | |
| In solvent | -80°C | 6 months |
| -20°C | 1 month |
Solvent & Solubility
DMSO : 20.83 mg/mL ( 64.54 mM ; Need ultrasonic)
Stock Solutions
| Concentration Solvent Mass | 1 mg | 5 mg | 10 mg |
|---|
| 1 mM | 3.0984 mL | 15.4919 mL | 30.9837 mL |
| 5 mM | 0.6197 mL | 3.0984 mL | 6.1967 mL |
| 10 mM | 0.3098 mL | 1.5492 mL | 3.0984 mL |
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Add each solvent one by one: 10% DMSO >> 90% corn oil
Solubility: ≥ 2.08 mg/mL (6.44 mM); Clear solution
References
- [1] Hideshima T, et al. NF-kappa B as a therapeutic target in multiple myeloma. J Biol Chem. 2002 May 10;277(19):16639-47.
- [2] Vodanovic-Jankovic S, et al. NF-kappaB as a target for the prevention of graft-versus-host disease: comparative efficacy of bortezomib and PS-1145. Blood. 2006 Jan 15;107(2):827-34.
- [3] Oh-I S, et al. Central administration of interleukin-4 exacerbates hypothalamic inflammation and weight gain during high-fat feeding. Am J Physiol Endocrinol Metab. 2010 Jul;299(1):E47-53.
Synonyms