Synonym
CCG-63802; CCG 63802; CCG63802; CCG-4986; CCG 4986; CCG4986
IUPAC/Chemical Name
(E)-2-(1,3-benzothiazol-2-yl)-3-[9-methyl-2-(3-methylphenoxy)-4-oxopyrido[1,2-a]pyrimidin-3-yl]prop-2-enenitrile
InChi Key
VFSVKVQMZDJFQX-NBVRZTHBSA-N
InChi Code
InChI=1S/C26H18N4O2S/c1-16-7-5-9-19(13-16)32-24-20(26(31)30-12-6-8-17(2)23(30)29-24)14-18(15-27)25-28-21-10-3-4-11-22(21)33-25/h3-14H,1-2H3/b18-14+
SMILES Code
N#C/C(C1=NC2=CC=CC=C2S1)=C\C3=C(OC4=CC=CC(C)=C4)N=C(C(C)=CC=C5)N5C3=O
Purity
>98% (or refer to the Certificate of Analysis)
Shipping Condition
Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition
Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility
Soluble in DMSO, not in water
Shelf Life
>2 years if stored properly
Drug Formulation
This drug may be formulated in DMSO
Stock Solution Storage
0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code
2934.99.9001
Biological target:
CCG-63802 is a selective, reversible and allosteric RGS4 inhibitor. CCG-63802 specifically binds to RGS4 and blocks the RGS4-Gαo interaction, with an IC50 value of 1.9 μM.
In vitro activity:
Two closely related compounds, typified by CCG-63802 [((2E)-2-(1,3-benzothiazol-2-yl)-3-[9-methyl-2-(3-methylphenoxy)-4-oxo-4H-pyrido[1,2-a]pyrimidin-3-yl]prop-2-enenitrile)], inhibit the interaction between RGS4 and Galpha(o) with an IC(50) value in the low micromolar range. They show selectivity among RGS proteins with a potency order of RGS 4 > 19 = 16 > 8 >> 7. The compounds inhibit the GTPase accelerating protein activity of RGS4, and thermal stability studies demonstrate binding to the RGS but not to Galpha(o). On RGS4, they depend on an interaction with one or more cysteines in a pocket that has previously been identified as an allosteric site for RGS regulation by acidic phospholipids. Unlike previous small-molecule RGS inhibitors identified to date, these compounds retain substantial activity under reducing conditions and are fully reversible on the 10-min time scale. CCG-63802 and related analogs represent a useful step toward the development of chemical tools for the study of RGS physiology.
Reference: Mol Pharmacol. 2010 Sep;78(3):524-33. https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/20571077/
In vivo activity:
Accompanied with OVA challenge, the mice received administration of PPARγ agonist PGZ (10 mg/kg) intragastrically or RGS4 inhibitor CCG 63802 (0.5 mg/kg) intratracheally. Invasive pulmonary function tests were performed 24 h after last challenge. Serum, bronchoalveolar lavage fluid (BALF), and lung tissues were collected for further analyses after the mice were sacrificed. It was found that PPARγ agonist PGZ administration significantly attenuated the pathophysiological features of OVA-induced asthma and increased the expression of RGS4. In addition, the attenuating effect of PGZ on airway inflammation, hyperresponsiveness (AHR), and remodeling was partially abrogated by administration of RGS4 inhibitor CCG 63802. It was also found that the downregulation of RGS4 by CCG 63802 also significantly increased inflammatory cell accumulation and AHR, and increased levels of IL-4, IL-13, eotaxin, IFN-γ, and IL-17A in BALF, and total and OV-specific IgE in serum. Furthermore, the inhibitory effects of PGZ on the activations of ERK and Akt/mTOR signaling, and MMPs were apparently reversed by CCG 63802 administration. In conclusion, the protective effect of PGZ on OVA-induced airway inflammation and remodeling might be partly regulated by RGS4 expression through ERK and Akt/mTOR signaling.
Reference: Inflammation. 2018 Dec;41(6):2079-2089. https://doi.org/10.1007/s10753-018-0851-2
|
Solvent |
mg/mL |
mM |
| Solubility |
| DMSO |
1.7 |
3.71 |
Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.
Preparing Stock Solutions
The following data is based on the
product
molecular weight
450.52
Batch specific molecular weights may vary
from batch to batch
due to the degree of hydration, which will
affect the solvent
volumes required to prepare stock solutions.
| Concentration / Solvent Volume / Mass |
1 mg |
5 mg |
10 mg |
| 1 mM |
1.15 mL |
5.76 mL |
11.51 mL |
| 5 mM |
0.23 mL |
1.15 mL |
2.3 mL |
| 10 mM |
0.12 mL |
0.58 mL |
1.15 mL |
| 50 mM |
0.02 mL |
0.12 mL |
0.23 mL |
In vitro protocol:
1. Blazer LL, Roman DL, Chung A, Larsen MJ, Greedy BM, Husbands SM, Neubig RR. Reversible, allosteric small-molecule inhibitors of regulator of G protein signaling proteins. Mol Pharmacol. 2010 Sep;78(3):524-33. doi: 10.1124/mol.110.065128. Epub 2010 Jun 22. PMID: 20571077; PMCID: PMC2939488.
2. Dobrivojević M, Sinđić A, Edemir B, Kalweit S, Forssmann WG, Hirsch JR. Interaction between bradykinin and natriuretic peptides via RGS protein activation in HEK-293 cells. Am J Physiol Cell Physiol. 2012 Dec 15;303(12):C1260-8. doi: 10.1152/ajpcell.00033.2012. Epub 2012 Oct 10. PMID: 23054060.
In vivo protocol:
1. Blazer LL, Roman DL, Chung A, Larsen MJ, Greedy BM, Husbands SM, Neubig RR. Reversible, allosteric small-molecule inhibitors of regulator of G protein signaling proteins. Mol Pharmacol. 2010 Sep;78(3):524-33. doi: 10.1124/mol.110.065128. Epub 2010 Jun 22. PMID: 20571077; PMCID: PMC2939488.
2. Dobrivojević M, Sinđić A, Edemir B, Kalweit S, Forssmann WG, Hirsch JR. Interaction between bradykinin and natriuretic peptides via RGS protein activation in HEK-293 cells. Am J Physiol Cell Physiol. 2012 Dec 15;303(12):C1260-8. doi: 10.1152/ajpcell.00033.2012. Epub 2012 Oct 10. PMID: 23054060.
1: Bosier B, Doyen PJ, Brolet A, Muccioli GG, Ahmed E, Desmet N, Hermans E,
Deumens R. Inhibition of the regulator of G protein signalling RGS4 in the spinal
cord decreases neuropathic hyperalgesia and restores cannabinoid CB1 receptor
signalling. Br J Pharmacol. 2015 Nov;172(22):5333-46. doi: 10.1111/bph.13324.
Epub 2015 Oct 25. PubMed PMID: 26478461.
2: Dobrivojević M, Sinđić A, Edemir B, Kalweit S, Forssmann WG, Hirsch JR.
Interaction between bradykinin and natriuretic peptides via RGS protein
activation in HEK-293 cells. Am J Physiol Cell Physiol. 2012 Dec
15;303(12):C1260-8. doi: 10.1152/ajpcell.00033.2012. Epub 2012 Oct 10. PubMed
PMID: 23054060.
3: Blazer LL, Roman DL, Chung A, Larsen MJ, Greedy BM, Husbands SM, Neubig RR.
Reversible, allosteric small-molecule inhibitors of regulator of G protein
signaling proteins. Mol Pharmacol. 2010 Sep;78(3):524-33. doi:
10.1124/mol.110.065128. Epub 2010 Jun 22. PubMed PMID: 20571077; PubMed Central
PMCID: PMC2939488.
