Some Free DD for the Stockhouse crowdIfenprodil = GRIN2B on Table 4 https://www.sciencedirect.com/science/article/pii/S088915912030670X?via%3Dihub#t0020 We also identified potential therapeutics for COVID-19 by intersecting the interactomes generated here with the DGIdb database (Cotto et al., 2018). We identified 144 gene products with characterized antagonists, inhibitors, blockers or modulators in this curated database (a selection of these are shown in Table 4, full dataset in Supplementary Table 8). This database highlights the potential for targeting cytokines and chemokines, such as CCL2, the CCR2 receptor and/or the EGFR receptor in COVID-19. It also reveals several drugs that interact with ephrin – EphB signaling that may have promise if structural remodeling of lung afferent endings contributes to COVID-19 pathology. Interestingly, the NMDA receptor 2B (GRIN2B) subunit was revealed in this list, which can be targeted with ketamine and other drugs. The corresponding gene GRIN2B was strongly induced in BALF samples of COVID-19 samples. The NMDA receptor is activated by glutamate, which is released by sensory neurons at their peripheral terminals. NMDA receptor activity and localization is strongly influenced by EphB receptors (Hanamura et al., 2017, Henderson and Dalva, 2018), which were also dramatically increased in COVID-19 BALF samples. These findings reveal a potential new pathway for sensory modulation of lung pathophysiology involving glutamate from sensory afferents acting on NMDA receptors expressed by resident cells in the lung.
Pair that with https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6906739/ Ifenprodil-targeted NMDA receptor genes and flavopiridol-targeted cyclin-dependent kinase 4 (CDK4) genes are linked to lung injury.
Ifenprodil is a selective N-methyl-d-aspartate (NMDA) receptor antagonist (20) and has been clinically used to treat neuronal injury and neurological disorders induced by overstimulation of the NMDA receptor (21). Our RNAi screening data revealed that knockdown of the NMDA receptor gene (GRIN2B) could alter the viability of H5N1-infected cells (Table S1). We obtained RNA sequencing data from lung tissues of H5N1-infected mice treated with ifenprodil and analyzed biological processes and pathways influenced by ifenprodil compared to vehicle control mice. We found that ifenprodil influenced the immune response and neurophysiological processes in the mouse lung (). Nine of the top 10 pathways of the ifenprodil treatment group were linked to the immune response (). Dozens of genes in most of the top 10 pathways were reported to be related to lung diseases as well as to traditional neuropathic indications of ifenprodil (; see also Table S4 in the supplemental material). Although previous reports indicated that NMDA receptors are expressed in lung tissues, that NMDA receptor signaling is linked to inflammation, and that overstimulation of the NMDA receptor can trigger lung injury (22, 23), our study revealed for the first time that ifenprodil is effective in avian influenza A H5N1 virus infection and lung injury.
AND....
Ifenprodil (1.5 mg/kg) showed a reduction of 42% in mean cough frequency vs untreated control (p <0.01).
Gefapixant (3.5 mg/kg) showed a 20% reduction in mean cough frequency vs untreated control (p <0.05).
Unlike Gefapixant, Ifenprodil has no known taste disturbance, which is similar to Bellus Health’s Phase 2 asset BLU-5937. Note: Bellus Health Inc. has reported that BLU-5937 had comparable efficacy to Merck’s MK-7264 (Gefapixant) in a guinea pig cough inhibition study that they conducted.
https://www.globenewswire.com/news-release/2019/12/05/1956652/0/en/Algernon-Pharmaceuticals-NP-120-Ifenprodil-Outperforms-Merck-s-Phase-3-Drug-MK-7264-Gefapixant-in-an-Acute-Cough-Study-by-110.html
There is even more measurable information in favor of Ifenpodil. What does this all tell you?
PS Stockhouse and Yahoo are worthless. The real conversations happen at https://investorshub.advfn.com/ and https://ceo.ca/agn
Cheers