Synonym
GW-842166X; GW842166X; GW 842166X; GW-842166; GW842166; GW 842166
IUPAC/Chemical Name
2-((2,4-dichlorophenyl)amino)-N-((tetrahydro-2H-pyran-4-yl)methyl)-4-(trifluoromethyl)pyrimidine-5-carboxamide
InChi Key
TWQYWUXBZHPIIV-UHFFFAOYSA-N
InChi Code
InChI=1S/C18H17Cl2F3N4O2/c19-11-1-2-14(13(20)7-11)26-17-25-9-12(15(27-17)18(21,22)23)16(28)24-8-10-3-5-29-6-4-10/h1-2,7,9-10H,3-6,8H2,(H,24,28)(H,25,26,27)
SMILES Code
O=C(C1=CN=C(NC2=CC=C(Cl)C=C2Cl)N=C1C(F)(F)F)NCC3CCOCC3
Purity
>95% (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
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:
GW842166X is a potent and selective cannabinoid receptor 2 (CB2) agonist with IC50 values of 63 and 91 nM for human and rat CB2, respectively.
In vivo activity:
The selective CB2 agonist GW842166x exerted neuroprotective effects against 6-hydroxydopamine (6-OHDA)-induced loss of dopaminergic terminals and dopamine release in the striatum, which were blocked by the CB2 antagonist AM630. 6-OHDA-treated mice exhibited anxiogenic- and depressive-like behaviors in the open-field, sucrose preference, novelty-suppressed feeding, marble burying, and forced swim tests but did not show significant changes in the elevated plus-maze and light-dark box test. GW842166x treatments ameliorated 6-OHDA-induced anxiogenic- and depressive-like behaviors, but the effects were blocked by CB2 antagonism, suggesting a CB2-dependent mechanism.
Reference: Biomedicines. 2022 Jul 22;10(8):1776. https://pubmed.ncbi.nlm.nih.gov/35892676/
|
Solvent |
mg/mL |
mM |
| Solubility |
| DMF |
20.0 |
44.52 |
| DMF:PBS (pH 7.2) (1:3) |
0.3 |
0.56 |
| DMSO |
37.8 |
84.07 |
| Ethanol |
0.3 |
0.67 |
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
449.25
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 |
Formulation protocol:
1. Liu X, Yu H, Chen B, Friedman V, Mu L, Kelly TJ, Ruiz-Pérez G, Zhao L, Bai X, Hillard CJ, Liu QS. CB2 Agonist GW842166x Protected against 6-OHDA-Induced Anxiogenic- and Depressive-Related Behaviors in Mice. Biomedicines. 2022 Jul 22;10(8):1776. doi: 10.3390/biomedicines10081776. PMID: 35892676; PMCID: PMC9329798.
2. Yu H, Liu X, Chen B, Vickstrom CR, Friedman V, Kelly TJ, Bai X, Zhao L, Hillard CJ, Liu QS. The Neuroprotective Effects of the CB2 Agonist GW842166x in the 6-OHDA Mouse Model of Parkinson's Disease. Cells. 2021 Dec 16;10(12):3548. doi: 10.3390/cells10123548. PMID: 34944056; PMCID: PMC8700250.
In vivo protocol:
1. Liu X, Yu H, Chen B, Friedman V, Mu L, Kelly TJ, Ruiz-Pérez G, Zhao L, Bai X, Hillard CJ, Liu QS. CB2 Agonist GW842166x Protected against 6-OHDA-Induced Anxiogenic- and Depressive-Related Behaviors in Mice. Biomedicines. 2022 Jul 22;10(8):1776. doi: 10.3390/biomedicines10081776. PMID: 35892676; PMCID: PMC9329798.
2. Yu H, Liu X, Chen B, Vickstrom CR, Friedman V, Kelly TJ, Bai X, Zhao L, Hillard CJ, Liu QS. The Neuroprotective Effects of the CB2 Agonist GW842166x in the 6-OHDA Mouse Model of Parkinson's Disease. Cells. 2021 Dec 16;10(12):3548. doi: 10.3390/cells10123548. PMID: 34944056; PMCID: PMC8700250.
1: Chen JJ, Han S, Cao Y, Chen JZ. The agonist binding mechanism of human CB2 receptor studied by molecular dynamics simulation, free energy calculation and 3D-QSAR studies. Yao Xue Xue Bao. 2013 Sep;48(9):1436-49. PubMed PMID: 24358778.
2: Petrov RR, Ferrini ME, Jaffar Z, Thompson CM, Roberts K, Diaz P. Design and evaluation of a novel fluorescent CB2 ligand as probe for receptor visualization in immune cells. Bioorg Med Chem Lett. 2011 Oct 1;21(19):5859-62. doi: 10.1016/j.bmcl.2011.07.099. PubMed PMID: 21855337; PubMed Central PMCID: PMC3171627.
3: Ostenfeld T, Price J, Albanese M, Bullman J, Guillard F, Meyer I, Leeson R, Costantin C, Ziviani L, Nocini PF, Milleri S. A randomized, controlled study to investigate the analgesic efficacy of single doses of the cannabinoid receptor-2 agonist GW842166, ibuprofen or placebo in patients with acute pain following third molar tooth extraction. Clin J Pain. 2011 Oct;27(8):668-76. doi: 10.1097/AJP.0b013e318219799a. PubMed PMID: 21540741.
4: Giblin GM, O'Shaughnessy CT, Naylor A, Mitchell WL, Eatherton AJ, Slingsby BP, Rawlings DA, Goldsmith P, Brown AJ, Haslam CP, Clayton NM, Wilson AW, Chessell IP, Wittington AR, Green R. Discovery of 2-[(2,4-dichlorophenyl)amino]-N-[(tetrahydro- 2H-pyran-4-yl)methyl]-4-(trifluoromethyl)- 5-pyrimidinecarboxamide, a selective CB2 receptor agonist for the treatment of inflammatory pain. J Med Chem. 2007 May 31;50(11):2597-600. PubMed PMID: 17477516.
