[CAS NO. 410074-60-1] CCG 203769
PRODUCTS SPECIFICATIONS [410074-60-1]
DESCRIPTION [410074-60-1]
Overview
| MDL | - |
|---|---|
| Molecular Weight | 202.27 |
| Molecular Formula | C8H14N2O2S |
| SMILES | O=C(N1CCCC)N(CC)SC1=O |
Summary
CCG 203769 is a selective G protein signaling ( RGS4 ) inhibitor, which blocks the RGS4-Gα o protein-protein interaction in vitro with an IC 50 of 17 nM.
IC50 & Target
|
RGS4 17 nM (IC 50 ) |
RGS19 140 nM (IC 50 ) |
RGS16 6 μM (IC 50 ) |
RGS8 79 μM (IC 50 ) |
GSK3β 5.4 μM (IC 50 ) |
In Vitro
CCG 203769 also displays dramatic selectivity (8- to >5000-fold) for RGS4 over other RGS proteins. CCG 203769 inhibits RGS19 with an IC 50 of 140 nM (8-fold selective for RGS4) and 6 μM for RGS16 (350-fold selective for RGS4). The closely related RGS8 is very weakly inhibited (IC 50 >60 μM) providing >4500-fold selectivity for RGS4. CCG 203769 inhibits GSK-3β with an IC 50 value of 5 μM. CCG 203769 does not inhibit the cysteine protease papain at 100 μM. CCG 203769 does not inhibit RGS7, which lacks cysteines in the RGS domain. CCG 203769 inhibits RGS/Gα o binding in an RGS-selective manner. CCG 203769 enhances Gα q -dependent cellular Ca 2+ signaling in an RGS4-dependent manner. CCG 203769 also blocks the GTPase accelerating protein (GAP) activity of RGS4. In single-turnover and steady-state GTPase experiments with Gα o and Gα i1 , the rate of GTP hydrolysis is strongly stimulated by RGS4, and this effect is inhibited by CCG 203769 with an IC 50 <1 μM [1] .
MCE has not independently confirmed the accuracy of these methods. They are for reference only.
In Vivo
To determine whether this genetic disruption of RGS4 function can be replicated pharmacologically, CCG 203769 is tested for effects on Carbamoylcholine chloride-mediated bradycardia in conscious, unrestrained rats. Carbamoylcholine chloride (0.1 mg/kg, IP) produces a modest decrease in heart rate compared to that of a saline vehicle control. CCG 203769 (10 mg/kg, IV) has no significant effect upon heart rate when given alone. However, CCG 203769, administered immediately prior to Carbamoylcholine chloride, significantly potentiates the bradycardic effect (p < 0.05). Given the functional role of RGS4 in Parkinson’s disease models, CCG 203769 is tested in a pharmacologic model of D2 antagonist-induced bradykinesia. Raclopride administration in rats causes increased hang time in the bar test, which is rapidly reversed by doses of CCG 203769 ranging from 0.1 to 10 mg/kg. The lowest dose, 0.01 mg/kg has no effect, while 0.1 mg/kg produces a submaximal effect. The higher doses, 1 and 10 mg/kg, produce equivalent effects. Similarly, the raclopride-induced paw drag in mice is reversed by 0.1-10 mg/kg CCG 203769 [1] .
MCE has not independently confirmed the accuracy of these methods. They are for reference only.
Appearance
Liquid
Shipping
Room temperature in continental US; may vary elsewhere.
Storage
| Pure form | -20°C | 3 years |
|---|---|---|
| 4°C | 2 years | |
| In solvent | -80°C | 6 months |
| -20°C | 1 month |
Solvent & Solubility
DMSO : 62.5 mg/mL ( 308.99 mM ; Need ultrasonic)
Stock Solutions
| Concentration Solvent Mass | 1 mg | 5 mg | 10 mg |
|---|
| 1 mM | 4.9439 mL | 24.7194 mL | 49.4389 mL |
| 5 mM | 0.9888 mL | 4.9439 mL | 9.8878 mL |
| 10 mM | 0.4944 mL | 2.4719 mL | 4.9439 mL |