Stroke Drug Development Targeting The GluN2B Subunit of NMDAR

NMDAR is a heterotetramer, and the GluN2 subunit, as its main component, mainly takes a part in modulating NMDAR ion channels. In particular, activation of glun2B-containing NMDARs accelerates neuronal death. This feature makes the regulation of NMDAR activity by regulating GluN2B subunits a hot research topic. Therefore, Ace Therapeutics provides a one-stop research platform to develop stroke drugs targeting the GluN2B subunit.

Screening & Validation of GluN2B Antagonists

Numerous studies have shown that GluN2B is closely associated with the pro-death pathway downstream of NMDAR. In view of its important role in NMDAR regulation, we also provide stroke drug development services targeting the GluN2B subunit. We first screen for small molecule compounds or peptides that disrupt the pro-death pathway involved in GluN2B, before testing the recovery effects of these drug candidates on stroke. Based on our ultra-large compound library, natural product library, and fragment library, we offer a complete screening service for GluN2B antagonists.

• For the GluN2B-PSD95-nNOS pathway, we screened for small molecules or interfering peptides that bind PSD95 or nNOS to inhibit NMDAR-mediated NO production and protect neurons from excitotoxicity.
• For the GluN2B-DAPK1 pathway, we screened small molecule inhibitors or interfering peptides targeting DAPK1 to disrupt GluN2B-DAPK1 interactions to protect neurons.
• For the GluN2B NMDAR-PTEN pathway, on the one hand, we offer the development of small molecule inhibitors or interfering peptides against Tat-K13, on the other hand, we offer the development of small molecule inhibitors or interfering peptides against PTEN.
• We offer various related protein and small molecule assays such as p53, PSD95, nNOS, NO, and Ca²⁺ with different detection techniques such as ELISA, biochemical reagents, western blotting, immunofluorescence, and chromatography assay.

Fig. 1 Neuronal death pathways targeting GluN2B and some of the inhibitors in development. (Wu, et al., 2018)

Evaluation of The Role of Candidates in Stroke

After screening candidate small molecules or peptides, it is important to test the effect of these drug candidates on recovery from stroke. In this regard, we offer different in vitro and in vivo stroke models, and we also provide appropriate testing services for the above models, including but not limited to biomarker assays and brain injury evaluation.

Biomarker Assays

• PSD95 content assays
• DAPK1 content assays
• PTEN content assays
• NO content assays

Brain Injury Evaluation

• Neuronal activity assays
• Laser scatter flow imaging
• Infarct volume measurement

Depending on the design of the experiment, we offer a personalized and customized service for the development of stroke drugs targeting the GluN2B subunit of NMDAR. If you would like to learn more about our services, please feel free to contact us.

1. Wu, Q. J. Tymianski, M., Targeting nmda receptors in stroke: New hope in neuroprotection. Mol Brain, 2018. 11(1): p. 15.
2. Ogden, K. K.Traynelis, S. F., New advances in nmda receptor pharmacology. Trends Pharmacol Sci, 2011. 32(12): p. 726-733.