CCG 203769

CCG 203769 is a selective G protein signaling (RGS4) inhibitor, which blocks the RGS4-Gαo protein-protein interaction in vitro with an IC50 of 17 nM.

Product information

CAS Number: 410074-60-1

Molecular Weight: 202.27

Formula: C8H14N2O2S

Chemical Name: 4-butyl-2-ethyl-1,2,4-thiadiazolidine-3,5-dione

Smiles: CCN1SC(=O)N(CCCC)C1=O

InChiKey: WTFFYZGCISALRI-UHFFFAOYSA-N

InChi: InChI=1S/C8H14N2O2S/c1-3-5-6-9-7(11)10(4-2)13-8(9)12/h3-6H2,1-2H3

Technical Data

Appearance: Solid Power

Purity: ≥98% (or refer to the Certificate of Analysis)

Solubility: DMSO : 62.5 mg/mL (308.99 mM; Need ultrasonic).

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical or refer to Certificate of Analysis

Storage Condition: Dry, dark and -20 ^oC for 1 year or refer to the Certificate of Analysis.

Shelf Life: ≥12 months if stored properly.

Stock Solution Storage: 0 - 4 ^oC for 1 month or refer to the Certificate of Analysis.

Drug Formulation: To be determined

HS Tariff Code: 382200

How to use

In Vitro:

CCG 203769 also displays dramatic selectivity (8- to >5000-fold) for RGS4 over other RGS proteins. CCG 203769 inhibits RGS19 with an IC50 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 (IC50>60 μM) providing >4500-fold selectivity for RGS4. CCG 203769 inhibits GSK-3β with an IC50 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/Gαo binding in an RGS-selective manner. CCG 203769 enhances Gαq-dependent cellular Ca2+ 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 Gαo and Gαi1, the rate of GTP hydrolysis is strongly stimulated by RGS4, and this effect is inhibited by CCG 203769 with an IC50<1 μM.

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.

Products are for research use only. Not for human use.