ADX88178 is a potent metabotropic glutamate receptor 4 positive allosteric modulator (PAM) (mGluR4 PAM) for human mGluR4 with EC50 of 4 nM.

Physicochemical Properties

Molecular Formula	C12H12N6S
Molecular Weight	272.328879356384
Exact Mass	272.084
CAS #	1235318-89-4
PubChem CID	46836872
Appearance	White to off-white solid powder
LogP	2.756
Hydrogen Bond Donor Count	2
Hydrogen Bond Acceptor Count	6
Rotatable Bond Count	3
Heavy Atom Count	19
Complexity	304
Defined Atom Stereocenter Count	0
InChi Key	MIQNXKWDQRNHAU-UHFFFAOYSA-N
InChi Code	InChI=1S/C12H12N6S/c1-7-3-4-13-11(16-7)18-12-17-10(8(2)19-12)9-5-14-15-6-9/h3-6H,1-2H3,(H,14,15)(H,13,16,17,18)
Chemical Name	5-methyl-N-(4-methylpyrimidin-2-yl)-4-(1H-pyrazol-4-yl)-1,3-thiazol-2-amine
HS Tariff Code	2934.99.9001
Storage	Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month
Shipping Condition	Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Biological Activity

ln Vitro	As a strong and targeted positive allosteric modulator of mGluR4, ADX88178 was created. The new radioligand ADX88178 is used to image the metabotropic glutamate receptor subtype 4 (mGluR4). With an EC50 value of 4 nM, ADX88178 increases glutamate-mediated activation of human mGluR4. Other mGluRs (EC50 > 30 μM) are not significantly affected by ADX88178 [1]. A new powerful, specific, and brain-penetrating mGlu4 positive allosteric modulator is ADX88178. After 30 minutes of pretreatment with 1, 10, or 100 nM ADX88178 or 100 nM LAP4, microglia were exposed to LPS during 24 hours. The culture supernatant was then removed for TNFα level determination using ELISA. The pretreatment of ADX88178 and LAP4 both considerably reduced the levels of TNFα generated by LPS. TNFα can be inhibited by ADX88178 at concentrations of only 1 nM, and it works just as well at 10 and 100 nM [2].
ln Vivo	In mice, ADX88178 (1-30 mg/kg po) dose-dependently enhanced the number of open-arm entries. Specifically, the number of open-arm entries rose 5-fold, 7-fold, and almost 13-fold at 3, 10, and 30 mg/kg ADX88178, respectively, compared to vehicle-treated controls. Furthermore, ADX88178 dose-dependently enhanced arm open time. Specifically, the time spent opening the arms increased 8-fold, 12-fold, and 24-fold at 3, 10, and 30 mg/kg ADX88178 compared to vehicle-treated controls. In rats, ADX88178 (10-100 mg/kg po) dose-dependently enhanced the number of open-arm entries in the rat EPM test. Specifically, the number of open-arm entry rose by more than 5-fold, 8-fold, and 10-fold at 10, 30, and 100 mg/kg ADX88178, respectively, compared to vehicle-treated controls. Furthermore, ADX88178 dose-dependently enhanced arm open time. Specifically, arm open time increased 7.5-, 11-, and 13-fold at 10, 30, and 100 mg/kg ADX88178 compared to vehicle-treated controls [3].
References	[1]. Radiosynthesis and evaluation of 5-methyl-N-(4-[(11)C]methylpyrimidin-2-yl)-4-(1H-pyrazol-4-yl)thiazol-2-amine ([(11)C]ADX88178) as a novel radioligand for imaging of metabotropic glutamate receptor subtype 4 (mGluR4). Bioorg Med Chem L. [2]. The Metabotropic Glutamate Receptor 4 Positive Allosteric Modulator ADX88178 Inhibits Inflammatory Responses in Primary Microglia. J Neuroimmune Pharmacol. 2016 Jun;11(2):231-7. [3]. Characterization of the novel positive allosteric modulator of the metabotropic glutamate receptor 4 ADX88178 in rodent models of neuropsychiatric disorders. J Pharmacol Exp Ther. 2014 Sep;350(3):495-505.

Solubility Data

Solubility (In Vitro)

DMSO : ~16.67 mg/mL (~61.21 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 1.67 mg/mL (6.13 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 16.7 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	3.6720 mL	18.3601 mL	36.7202 mL
	5 mM	0.7344 mL	3.6720 mL	7.3440 mL
	10 mM	0.3672 mL	1.8360 mL	3.6720 mL

*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.