ArticleActa biochimica et biophysica Sinica2022
A novel small positive allosteric modulator of neuropeptide receptor PAC1-R exerts neuroprotective effects in MPTP mouse Parkinson's disease model.
Article in Acta biochimica et biophysica Sinica, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
2 citing papers in PubMed, 4 citations in OpenAlex.
- Integrated Transcriptomic and Proteomic Study of the Mechanism of Action of the Novel Small-Molecule Positive Allosteric Modulator 1 in Targeting PAC1-R for the Treatment of D-Gal-Induced Aging Mice.International journal of molecular sciences · 2024Article
- Novel Small Molecule Positive Allosteric Modulator SPAM1 Triggers the Nuclear Translocation of PAC1-R to Exert Neuroprotective Effects through Neuron-Restrictive Silencer Factor.International journal of molecular sciences · 2022Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
As a neuropeptide pituitary adenylate cyclase-activating polypeptide (PACAP)-preferring receptor, PAC1-R mediates effective neuroprotective activity. Based on the finding that the antibiotic doxycycline (DOX) with clinical neuroprotective activity functions as a positive allosteric modulator (PAM) of neuropeptide PACAP receptor 1 (PAC1-R), we use virtual and laboratory screening to search for novel small molecule PAMs of PAC1-R. Virtual screening is carried out using a small-molecule library TargetMol. After two-level precision screening with Glide, the top five compounds with the best predicted affinities for PAC1-R are selected and named small positive allosteric modulator 1‒5 (SPAM1‒5). Our results show that only 4-{[4-(4-Oxo-3,4-2-yl)butanamido]methyl}benzoic acid (SPAM1) has stronger neuroprotective activity than DOX in the MPP+ PD cell model and MPTP PD mouse model. SPAM1 has a higher affinity for PAC1-R than DOX, but has no antibiotic activity. Moreover, both SPAM1 and DOX block the decrease of PAC1-R level in mouse brain tissues induced by MPTP. The successful screening of SPAM1 offers a novel drug for the treatment of neurodegenerative disease targeting the PAC1-R.
Indexed as
Identifiers
What Socratic holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.