ADX88178

SKU: orb1302808

Description

ADX88178 is a highly potent and selective positive allosteric modulator of the metabotropic glutamate receptor 4 (mGluR4), exhibiting an EC50 of 4 nM at the human receptor. This compound is a valuable research tool for investigating mGluR4 function in models of Parkinson's disease and other neurological disorders, supporting both in vitro and in vivo experimental applications.

Research Area

Neuroscience

Key Properties

• CAS Number: 1235318-89-4
• MW: 272.33
• Purity: 99.55% (May vary between batches)
• Formula: C₁₂H₁₂N₆S
• SMILES: Cc1sc(Nc2nccc(C)n2)nc1-c1cn[nH]c1
• Target: GluR
• Solubility: DMSO:22.5 mg/mL (82.62 mM);10% DMSO+90% Saline:1.5 mg/mL (5.51 mM)

Bioactivity

• Target IC50:
  mGluR4 (human):4 nM(EC50)
• In Vivo:
  In rats, ADX88178 (10-100 mg/kg p.o.) dose-dependently increases the number of open-arm entries in the rat EPM test. Specifically, at 10, 30, and 100 mg/kg ADX88178, there are 5-, 8-, and more than 10-fold increases in the number of open-arm entries, respectively, when compared with the vehicle-treated controls. Also, ADX88178 dose-dependently increases the time spent in the open arms. Specifically, at 10, 30, and 100 mg/kg ADX88178, there are 7.5-, 11-, and 13-fold increases in time spent in the open arms when compared with the vehicle-treated controls.
• In Vitro:
  ADX88178 is used as a novel radioligand for imaging of metabotropic glutamate receptor subtype 4 (mGluR4). ADX88178 potentiates glutamate-mediated activation of human mGluR4 with EC50 values of 4 nM without significant effects on other mGluRs (EC50 > 30 μM). Microglia are pretreated with 1, 10 or 100 nM ADX88178 or 100 nM LAP4 for 30 min followed by LPS treatment for 24 h prior to collecting culture supernatant for ELISA measurement of TNFα levels. The pre-treatment with ADX88178 and LAP4 both significantly attenuate LPS-induced TNFα levels. As little as 1 nM of ADX88178 is sufficient to inhibit TNFα, and is as effective at concentrations of 10 and 100 nM.
• Cell Research:
  ADX88178 is dissolved in DMSO and stored, and then diluted with appropriate medium before use. After adhesion to the chamber slides, microglia from WT and mGlu4 KO microglia pre-treated with 1 nM, 10 nM, 100 nM ADX88178, or 100 nM L-AP4. Each treatment is performed in quadruplicate. Thirty minutes after treatment with ADX88178 or L-AP4, 100 ng/mL LPS is added to the cultures and the cells are incubated at 37 °C for an additional 24 h. At the end of the 24 h treatment period, media is collected and analyzed for TNFα, and the cells are for iNOS and MHC II expression by immunocytochemistry.
• Animal Research:
  Mice and Rat Male mice (n=8-10/group) are treated orally (p.o.) via gavage with vehicle [1% carboxymethyl cellulose (CMC)], ADX88178 (1, 3, 10 and 30 mg/kg) or Diazepam (1.5 mg/kg). Male rats (n=10/group) are treated p.o. with vehicle (1% CMC), ADX88178 (10, 30, and 100 mg/kg), or Diazepam (3 mg/kg). After 60 minutes, animals are individually placed in the center of the maze (facing one of the closed arms) and left to explore for 5 minutes. A terminal blood sample is collected from all ADX88178-treated animals at the end of the experiment, and plasma is analyzed for the pharmacokinetic studies. The number of open-arm and closed-arm entries, as well as the time (seconds) spent in the open arms of the maze, is analyzed by one-way analysis of variance followed by Dunnett's test.

Storage & Handling

• Storage: Powder: -20°C for 3 years | In solvent: -80°C for 1 year | Shipping with blue ice/Shipping at ambient temperature.
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

ADX 88178, ADX88178, ADX-88178, mGluR, mGluR4 (Human), Metabotropic glutamate receptors, inhibit, Inhibitor

Compound Identifiers

PubChem CID

46836872