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simvastatin (simvastatin, Hanmi / simvastatin CR / Simvast CR)

✓ Approved

Hanmi Pharmaceutical · HMGCR · Small Molecule

What is simvastatin?

simvastatin is a small molecule developed by Hanmi Pharmaceutical. It is approved for therapeutic indications via oral (po).

Drug Profile

Brand Namessimvastatin, Hanmi, simvastatin CR, Simvast CR
CompanyHanmi Pharmaceutical
Drug ClassSmall Molecule
Molecular TargetHMGCR
RouteOral (PO)
StatusApproved
Sources: ClinicalTrials.gov, Hanmi Pharmaceutical

Mechanism of Action

Molecular Targets

simvastatin acts on 1 molecular target:

HMGCR3-hydroxy-3-methylglutaryl-CoA reductase (LDLCQ3, LGMDR28)
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Therapeutic Indications

simvastatin is developed for 1 unique indication across 1 therapeutic area.

Therapeutic AreaConditionPhase
Metabolism and nutrition disordersHyperlipidaemia✓ Approved

Related Research Articles

PubMedNutrients2026-09-15

Polyphenol-Rich Opuntia ficus-indica Cladodes: An Integrated Metabolomic, In Vivo and In Silico Study Supporting Their Hypolipidemic and Hepatoprotective Effects.

Hadini Abderrahmane A, Addous Abdelhay A, Baraich Abdellah A, Bendada Mourad M et al.

Background: Hyperlipidemia is a major risk factor for cardiometabolic disorders, including non-alcoholic fatty liver disease (NAFLD), and is closely associated with oxidative stress. Opuntia ficus-indica (OFI) cladodes are recognized as a rich source of bioactive phytochemicals; however, the molecular mechanisms underlying their metabolic benefits remain incompletely understood. Objectives: This study aimed to comprehensively evaluate the hypolipidemic and hepatoprotective potential of a polyphenol-rich O. ficus-indica cladode extract (OCE) using an integrated approach combining in vivo evaluation, untargeted metabolomics (UHPLC-Orbitrap-MS/MS), molecular docking, and ADMET prediction. Methods: Hyperlipidemic mice fed a high-fat diet (HFD) were treated with OCE, while molecular docking was performed on ten major annotated phytochemicals against twelve key proteins involved in lipid metabolism and cholesterol homeostasis, including HMGCR, FAS, PPARα, PCSK9, and NPC1L1, using simvastatin as the reference compound. Results: OCE treatment significantly improved plasma and hepatic lipid profiles, improved glucose homeostasis, and markedly reduced hepatic malondialdehyde (MDA) levels, indicating attenuation of oxidative stress. Histopathological analysis further supported a pronounced hepatoprotective effect, with a substantial reduction in hepatic steatosis. Untargeted metabolomics enabled the annotation of 102 metabolites, putatively identifying piscidic acid as the predominant phenolic constituent together with a diverse profile of flavonoids and phenolic acids. Molecular docking supported the potential contribution of these phytochemicals to the regulation of lipid metabolism through favorable interactions with multiple therapeutic targets, while ADMET prediction suggested an overall favorable pharmacokinetic and toxicity profile despite the lower intestinal permeability predicted for glycosylated derivatives. Conclusions: Overall, these findings support O. ficus-indica cladodes as a promising source of dietary bioactive compounds with potential applications in the nutritional management and prevention of hyperlipidemia and related cardiometabolic disorders.

PMID 42738940
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PubMedEuropean endodontic journal2026-09-13

The Influence of Simvastatin on the Osteogenic Differentiation Induced by Calcium Silicate-Based Cements.

Di Giorgio Gianni G, Straface Gianluca G, Cialfi Samantha S, Talora Claudio C et al.

The combination of simvastatin with hydraulic materials might offer added benefits for enhancing mineralisation, reducing inflammation, and supporting pulp healing. Therefore, the aim of the present in vitro study was to assess the effect of hydraulic calcium silicate-based cements in addition to simvastatin on cell viability and osteogenic differentiation. Human osteogenic sarcoma (Saos-2) cells were cultured in presence of 0.1 μM of simvastatin, and with ProRoot MTA (Mineral Trioxide Aggregate) and Biodentine in combination or not with simvastatin. Cell viability was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay at 24, 48, and 72 hours and immunofluorescence microscopy analysis was conducted after 72 hours. Osteogenic differentiation was evaluated by Alizarin Red Staining (ARS) after 18 days. Moreover, gene expression (RUNX-2, COL1A1, ALP, OCN) was analysed at 12 and 18 days. Statistical analysis was performed using analysis of variance, Bonferroni's test, and Student's tests. Simvastatin at 0.1 μM preserved cell viability comparable to that of the untreated control. Lesser cytotoxicity was reported when simvastatin was combined with Biodentine, rather than ProRoot MTA. Simvastatin alone or in combination with both cements induced the reorganisation of the actin cytoskeleton into lamellipodia. Alizarin Red Staining showed that simvastatin significantly enhanced mineralisation, mainly when combined with Biodentine. Conversely, both cements alone showed moderate effects. Regarding gene expression, analyses revealed that these materials, in addition to simvastatin, influenced differently osteogenic markers, suggesting the involvement of distinct molecular pathways probably due to different chemical composition. Hydraulic calcium silicate-based cements exhibited distinct effects on the expression of differentiation-related genes, while showing a comparable influence on mineralisation nodule deposition. These findings suggest material-specific biological responses when the cements are combined with simvastatin.

PMID 42732573
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PubMedAnnals of the American Thoracic Society2026-09-13

Heterogeneity of Treatment Effect by Molecular Endotype in Acute Respiratory Distress Syndrome: A Systematic Review.

Van Nynatten Logan R LR, McChesney Christopher C, Basharat Mujtaba M, Fraser Douglas D DD et al.

Despite numerous randomized controlled trials (RCTs) in acute respiratory distress syndrome (ARDS), few have identified effective therapies. One reason may be heterogeneity of treatment effect (HTE), in which distinct subgroups respond differently to the same intervention, potentially reflective of underlying biological endotypes. We conducted a systematic review to evaluate effect modification by molecular endotype across randomized ARDS trials and assess credibility of reported subgroup effects. In doing so, we aim to expose current knowledge gaps in how subgroups are defined and inform future clinical practice guideline recommendations. Following PRISMA guidelines, we searched OVID Medline, Embase, and the Cochrane Central Register of Controlled Trials for secondary and post-hoc analyses of RCTs in adult critically-ill patients with ARDS that evaluated treatment effects stratified by molecular endotype. We evaluated subgroup credibility using the Instrument to assess the Credibility of Effect Modification Analyses (ICEMAN). Eleven secondary analyses from ten RCTs (5,514 participants) were included. Most studies identified two reproducible endotypes, hyperinflammatory and hypoinflammatory, using small panels of circulating protein biomarkers. Of 11 analyses, four demonstrated statistically significant effect modification (higher PEEP, liberal fluid strategy, vv-ECCO₂R, simvastatin). The hyperinflammatory endotype drove every observed interaction, though the direction varied by intervention. The most credible subgroup effect was observed with liberal fluid strategy in hyperinflammatory ARDS (high credibility), followed by simvastatin and vv-ECCO₂R (moderate credibility). Endotyping in ARDS reliably identifies biologically distinct patient groups, but evidence that endotypes consistently modify treatment response is sparse and of generally low credibility. Progress toward endotype-guided therapy will require multi-omic molecular characterization, prospective trials with pre-specified interaction hypotheses, and real-time endotype assignment.

PMID 42730647
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PubMedThe AAPS journal2026-09-10

Verification of a Physiologically-based Pharmacokinetic Model for Predicting CYP3A4-mediated Simvastatin and Simvastatin Acid Drug-drug Interactions.

Morse Bridget L BL, Han Bing B, Alberts Jeffrey J JJ, Posada Maria M MM et al.

Simvastatin is a commonly prescribed medication and a sensitive CYP3A4 substrate requiring dosage modification with CYP3A4 precipitants. Unlike other CYP3A4 substrates, grapefruit juice (GFJ) causes the largest increase in simvastatin exposure of any CYP3A4 inhibitor, leading to misunderstanding of simvastatin fraction escaping CYP3A4 metabolism in the gut (Fg, CYP3A4) and fraction metabolized by CYP3A4 in the liver (fm,CYP3A4). Simvastatin is a prodrug that is converted to the active simvastatin acid, though the mechanisms responsible for in vivo simvastatin acid formation are not well-understood. GFJ also decreases the simvastatin acid:simvastatin exposure ratio, suggesting inhibition of simvastatin acid formation. In the current work, we used a static approach to define simvastatin CYP3A4 parameters, using clinical data with index substrate midazolam; estimated simvastatin Fg,CYP3A4 and fm,CYP3A4 were ~ 0.4 and ~ 0.9, respectively. In vitro data assessing the stability of simvastatin and simvastatin acid demonstrated rapid conversion in gastric fluid that was highly pH-dependent. A simvastatin PBPK model was constructed incorporating these CYP3A4 parameters and simvastatin acid formation in stomach, intestine and plasma. The model reproduced the nonlinear pharmacokinetics of simvastatin and CYP3A4 precipitant effects, thus qualifying the model for prediction of CYP3A4-mediated interactions on both simvastatin and simvastatin acid. Simvastatin overall Fg was estimated as ~ 0.2, lower than the Fg,CYP3A4 due to additional intestinal esterase-mediated formation of simvastatin acid. The simvastatin-GFJ effect was explained by inhibition of this intestinal simvastatin acid formation, along with CYP3A4 inhibition. The unique effect of food on the simvastatin acid:simvastatin exposure ratio could also be replicated using this PBPK model.

PMID 42717157
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PubMedOncology letters2026-09-08

[Expression of Concern] Simvastatin potentiates doxorubicin activity against MCF-7 breast cancer cells.

Buranrat Benjaporn B, Suwannaloet Wanwisa W, Naowaboot Jarinyaporn J

PMID 42707441
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PubMedPhytotherapy research : PTR2026-09-08

Protosappanin A Alleviates Atherosclerosis by Regulating the MDM2/GPX4 Axis-Mediated Endothelial Ferroptosis.

Fu Jiamei J, Zhu Lin L, Yang Wenwei W, Li Mengnan M et al.

Endothelial ferroptosis is a crucial pathogenic driver of atherosclerosis (AS) progression. Protosappanin A (PTA), a bioactive compound from Caesalpinia sappan L., protects cardiovascular vessels by regulating ferroptosis. However, whether PTA inhibits AS specifically through suppressing endothelial ferroptosis remains unclear. To address this, ApoE-/- mice were fed a high-fat diet for 16 weeks to induce atherosclerosis, and PTA or simvastatin was administered daily from Week 4 through Week 16 (12 weeks of intervention). PTA markedly reduced aortic plaque area (en face Oil Red O and H&E staining) and improved serum lipid profiles (TG, TC, LDL-C, HDL-C). It also alleviated endothelial injury, evidenced by decreased VCAM-1 and ICAM-1 expression. Mechanistically, PTA ameliorated mitochondrial ferroptosis in endothelial cells, lowered intracellular Fe2+ and lipid peroxidation (MDA, lipid ROS), and restored the expression of GPX4, xCT, and FTH1. Immunofluorescence confirmed that PTA upregulated GPX4 within the aortic endothelium. To explore the underlying mechanism, we performed RNA-seq on ox-LDL-treated HUVECs and integrated the data with ferroptosis-related databases. MDM2 was identified as a key target, which was validated by qPCR and Western blotting. Overexpression of MDM2 activated endothelial ferroptosis and reversed the protective effects of PTA both in vitro and in vivo. Collectively, these findings demonstrate that PTA alleviates AS by suppressing endothelial ferroptosis via the MDM2/GPX4 axis.

PMID 42711266
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