ArticleJournal of advanced research2026
Identification and evaluation of a lipid-lowering small compound as a PCSK9 inhibitor.
Article in Journal of advanced research, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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
0 citing papers in PubMed.
No citing paper in PubMed yet.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
18 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
introductionHyperlipidemia is a key contributor to cardiovascular diseases, underscoring the necessity for alternative lipid-lowering treatments beyond statins.
objectivesThis study aimed to synthesize and identify small, low-toxicity lipid-lowering compounds and investigate their mechanisms of action.
methodsA series of tetrahydroisoquinoline compounds were synthesized, with HepG2 cells used to screen and identify B11 as a potent, low-toxicity lipid-lowering candidate. B11's efficacy was tested in various hyperlipidemic animal models, including C57BL/6 mice, hamsters, and humanized PCSK9 transgenic (B6-hPCSK9) mice. Target interactions were investigated using various in vitro techniques, including molecular docking, cellular thermal shift assays (CETSA), drug affinity responsive target stability (DARTS), and surface plasmon resonance (SPR). Furthermore, we evaluated the synergistic effects of B11 combined with statins in C57BL/6 mice.
resultsA series of tetrahydroisoquinoline compounds was synthesized, identifying B11 as a potent lipid-lowering candidate with minimal toxicity. B11 significantly reduced total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and triglycerides (TG) in the plasma and liver of high fat diet (HFD) induced mice, hamsters, and B6-hPCSK9 mice, without causing any adverse effects. Mechanistically, B11 targets the 455-692 amino acid region of pro-protein convertase subtilisin/kexin type 9 (PCSK9), blocking its interaction with the low-density lipoprotein receptor (LDL-R) and inducing PCSK9 degradation via the ubiquitin-proteasome pathway. This process leads to increased LDL-R levels, enhancing LDL-C clearance. Notably, The unique mechanism of B11 enables combination therapy with atorvastatin, leading to stronger lipid-lowering effects and lower liver toxicity.
conclusionsThese findings demonstrate a small, non-statin compounds, and provide the potential alternative treatment approach for hyperlipidemic patients.
Indexed as
Identifiers
What OpenQuestion 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 OpenQuestion graph.