[CAS NO. 210354-22-6] GW274150
PRODUCTS SPECIFICATIONS [210354-22-6]
DESCRIPTION [210354-22-6]
Overview
| MDL | - |
|---|---|
| Molecular Weight | 219.30 |
| Molecular Formula | C8H17N3O2S |
| SMILES | N[C@@H](CCSCCNC(C)=N)C(O)=O |
1 Publications Citing Use of MCE
Summary
GW274150 is a potent, selective, orally active and NADPH-dependent inhibitor of human inducible nitric oxide synthase (iNOS) ( IC 50 =2.19 μM; K d =40 nM) and rat iNOS ( ED 50 =1.15 μM). GW274150 also displays less potency for both humans or rats endothelial NOS ( eNOS ) and neuronal NOS ( nNOS ). GW274150 exerts a protective role in an acute model of lung injury inflammation [1] [2] .
IC50 & Target
In Vitro
GW274150 inhibits intracellular iNOS in J774 cells in a time-dependent manner, reaching IC
50
values of 0.2 μM
[1]
.
GW274150 is >260-fold and 219-fold selective for iNOS against eNOS and nNOS in rat tissues, respectively. And it displays >100-fold and >80-fold for human iNOS against human eNOS and nNOS, respectively
[1]
.
MCE has not independently confirmed the accuracy of these methods. They are for reference only.
In Vivo
GW274150 is a long-acting (5 h half‐life in rats) iNOS inhibitor and is able to inhibit LPS‐mediated increase in plasma NO2
-
, NO3
-
levels 14 h after single intraperitoneal dose (ED
50
=3 mg/kg)
[2]
.
GW274150 (intraperitoneal injection; 2.5, 5, and 10 mg/kg; before carrageenan injection) reduces the degree of lung injury induced by carrageenan in a dose-related fashion. Oedema formation and PMNs infiltration in the pleural cavity are also significantly attenuated in a dose‐related manner in rats
[2]
.
GW274150 (oral adminstration; 30 mg/kg; twice daily; 7 days) leads to significant neuroprotection, However, it displays a bell-shaped neuroprotective profile, being ineffective at high doses in 6-OHDA rat model of Parkinson disease (PD)
[3]
.
MCE has not independently confirmed the accuracy of these methods. They are for reference only.
| Animal Model: | SD-rat [2] |
| Dosage: | 2.5, 5 and 10 mg/kg; single dose |
| Administration: | Intraperitoneal injection 5 min before carrageenan injection |
| Result: | Exerted a protective role in an acute model of inflammation, carrageenan-induced lung injury. |
Clinical Trial
| NCT Number | Sponsor | Condition | Start Date | Phase |
|---|---|---|---|---|
| NCT00370435 | GlaxoSmithKline |
Arthritis, Rheumatoid
|
August 2005 | Phase 2 |
| NCT00242866 | GlaxoSmithKline |
Migraine Disorders
|
October 2005 | Phase 2 |
| NCT00379990 | GlaxoSmithKline |
Arthritis, Rheumatoid
|
January 2006 | Phase 2 |
| NCT00319137 | GlaxoSmithKline |
Migraine Disorders|Migraine
|
December 2005 | Phase 2 |
| NCT00273013 | GlaxoSmithKline |
Asthma
|
November 15, 2004 | Phase 1 |
Shipping
Room temperature in continental US; may vary elsewhere.
Storage
Please store the product under the recommended conditions in the Certificate of Analysis.
Solvent & Solubility
H 2 O : ≥ 62 mg/mL ( 282.72 mM )
DMSO : < 1 mg/mL (insoluble or slightly soluble)
* "≥" means soluble, but saturation unknown.
Stock Solutions
| Concentration Solvent Mass | 1 mg | 5 mg | 10 mg |
|---|
| 1 mM | 4.5600 mL | 22.7998 mL | 45.5996 mL |
| 5 mM | 0.9120 mL | 4.5600 mL | 9.1199 mL |
| 10 mM | 0.4560 mL | 2.2800 mL | 4.5600 mL |
References
- [1] Alderton WK, et al. GW274150 and GW273629 are potent and highly selective inhibitors of inducible nitric oxide synthase in vitro and in vivo.Br J Pharmacol. 2005 Jun;145(3):301-12.
- [2] Dugo L, et al. Effects of GW274150, a novel and selective inhibitor of iNOS activity, in acute lung inflammation. Br J Pharmacol. 2004 Mar;141(6):979-87. Epub 2004 Feb
- [3] Broom L, et al. Neuroprotection by the selective iNOS inhibitor GW274150 in a model of Parkinson disease.Free Radic Biol Med. 2011 Mar 1;50(5):633-40.
Synonyms
