Figure 1. Whole cell and single channel recordings in response to rapid agonist application; UBP684 effects on responses by GluN1/GIuN2A receptors expressed in HEK cell.
(A) An NMDAR current evoked by a short pulse of glutamate (30 µM). With (red trace) and black trace (without) 30 µM of UBPE84. (B) Effect on NMDAR single channel currents (representative traces from patch believed to contain only one channel), elicited by a short pulse of glutamate. Data from Sapkota et al (2017) Neuropharmacology 125:64-79.
Figure 1. Whole cell and single channel recordings in response to rapid agonist application; UBP684 effects on responses by GluN1/GIuN2A receptors expressed in HEK cell.
(A) An NMDAR current evoked by a short pulse of glutamate (30 µM). With (red trace) and black trace (without) 30 µM of UBPE84. (B) Effect on NMDAR single channel currents (representative traces from patch believed to contain only one channel), elicited by a short pulse of glutamate. Data from Sapkota et al (2017) Neuropharmacology 125:64-79.
Biological Data
Biological description
UBP684 is a novel NMDAR PAM (positive allosteric modulator) which robustly potentiates responses at all GluN1/GluN2 subtypes and at neuronal NMDARs. UBP684 increases the maximal l-glutamate/glycine response while having minor subunit-specific effects on agonist potency.
UBP684 increases NMDAR channel open probability (Po) and slows receptor deactivation time upon removal of L-glutamate but not glycine.
Docking studies suggest that UBP684 binds to the GluN1 and GluN2 LBD (ligand binding domain) interface supporting its potential ability in stabilizing the LBD closed conformation.
UBP684 binding is independent of agonist binding and its activity is independent of membrane voltage and redox state. UBP684 activity is also pH-dependent, with enhanced potentiation at lower pHs and inhibitory activity at high pH (e.g.8.4).
Solubility & Handling
Storage instructions
-20°C
Solubility overview
Soluble in DMSO (100 mM)
Handling
University of Nebraska researchers recommend making up UBP684 as a 50 mM stock solution in DMSO and diluting it into physiological buffer up to 50 µM.
Please note that UBP684 is less soluble in physiological buffers that have mM levels of calcium.
UBP684 can be used in buffers usually used for studying NMDAR responses in Xenopus oocytes, however it may not work well in buffers used to investigate synaptic transmission.
Calcium-free buffers can be used to improve compound solubility.
Important
This product is for RESEARCH USE ONLY and is not intended for therapeutic or diagnostic use. Not for human or veterinary use
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