[CAS NO. 862892-90-8] GSK256073
PRODUCTS SPECIFICATIONS [862892-90-8]
DESCRIPTION [862892-90-8]
Overview
| MDL | - |
|---|---|
| Molecular Weight | 256.69 |
| Molecular Formula | C10H13ClN4O2 |
| SMILES | O=C(N(C1=C2NC(Cl)=N1)CCCCC)NC2=O |
Summary
GSK256073 is a potent, selective and orally active GPR109A agonist and a long-lasting and non-flushing HCA2 full agonist with a pEC 50 of 7.5 (human HCA2). GSK256073 acutely improves glucose homeostasis via inhibition of lipolysis and has the potential for the study of type 2 diabetes mellitus (T2DM)and dyslipidemia [1] [2] . GPR109A: G-protein coupled receptor 109A; HCA2: hydroxy-carboxylic acid receptor 2
IC50 & Target
In Vitro
GSK256073 is approximately 10-fold more potent than niacin against human HCA2 (pEC
50
value of 7.5 compared to 6.7 for niacin), has good activity versus the rat orthologue of HCA2 (pEC
50
value of 6.9 compared to 6.4 for niacin) in membranes prepared from Chinese hamster ovary cellsexpressing recombinant human HCA2
[2]
.
GSK256073 (100 μM) suppresses cAMP elevation induced by isoprenaline (100 nM) in rat primary adipocytes
[2]
.
MCE has not independently confirmed the accuracy of these methods. They are for reference only.
In Vivo
GSK256073 (oral adminstration; 1, 30 and 100 mg/kg; in rat) shows that the fall in NEFA is of rapid onset and that the maximum is dose-related with inhibitions of 74, 81 and 88%, respectively. Triglycerides decrease is followed as a similar pattern,although the duration was longer with a decrease of 91% still present 6 h post dose at 10 mg/kg
[2]
.
GSK256073 (intravenous injection; 1-10 mg/kg) produces a dose related decrease in NEFA. However, the increase in ear temperature induced by 10 mg/kg i.v. GSK256073 is only 40% of that induced by 10 mg/kg i.v. niacin
[2]
.
MCE has not independently confirmed the accuracy of these methods. They are for reference only.
| Animal Model: | SD rat [2] |
| Dosage: | 1, 30 and 100 mg/kg |
| Administration: | Oral adminstration |
| Result: | Inhibited NEFA expression as a dose-dependent manner. |
| Animal Model: | Guinea pigs [2] |
| Dosage: | 10 mg/kg |
| Administration: | Intravenous injection |
| Result: | Had the antilipolytic and flushing effects as a HCA2 agonist. |
Clinical Trial
| NCT Number | Sponsor | Condition | Start Date | Phase |
|---|---|---|---|---|
| NCT00903617 | GlaxoSmithKline |
Dyslipidaemias|Dyslipidemias
|
June 15, 2009 | Phase 2 |
| NCT01147861 | GlaxoSmithKline |
Diabetes Mellitus, Type 2
|
July 1, 2010 | Phase 1 |
| NCT01376323 | GlaxoSmithKline |
Diabetes Mellitus, Type 2
|
July 13, 2011 | Phase 2 |
| NCT00808093 | GlaxoSmithKline |
Dyslipidaemias
|
May 12, 2008 | Phase 1 |
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 : 16.67 mg/mL ( 64.94 mM ; Need ultrasonic)
Stock Solutions
| Concentration Solvent Mass | 1 mg | 5 mg | 10 mg |
|---|
| 1 mM | 3.8957 mL | 19.4787 mL | 38.9575 mL |
| 5 mM | 0.7791 mL | 3.8957 mL | 7.7915 mL |
| 10 mM | 0.3896 mL | 1.9479 mL | 3.8957 mL |
-
1.
Add each solvent one by one: 10% DMSO >> 90% corn oil
Solubility: ≥ 1.67 mg/mL (6.51 mM); Clear solution
References
- [1] Dobbins RL, et al. GSK256073, a selective agonist of G-protein coupled receptor 109A (GPR109A) reduces serum glucose in subjects with type 2 diabetes mellitus.Diabetes Obes Metab. 2013 Nov;15(11):1013-21.
- [2] Sprecher D, et al. Discovery and characterization of GSK256073, a non-flushing hydroxy-carboxylic acid receptor 2 (HCA2) agonist.Eur J Pharmacol. 2015 Jun 5;756:1-7.