Drug Database
SI

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)
Want deeper analysis?Noah AI can explain complex mechanisms and compare to similar drugs.

Therapeutic Indications

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

Therapeutic AreaConditionPhase
Metabolism and nutrition disordersHyperlipidaemia✓ Approved

Related Research Articles

PubMedAdvanced science (Weinheim, Baden-Wurttemberg, Germany)2026-10-15

Loss of Intestinal MSTN Promotes GLP-1 Secretion Through SGLT1 Palmitoylation.

Han Sheng-Zhong SZ, Chang Shuang-Yan SY, Luo Zhaobo Z, Sun Ke K et al.

Intestinal glucagon-like peptide-1 (GLP-1) is secreted by intestinal L cells in a glucose-dependent manner. The localization and surface abundance of glucose-sensing proteins on the cell membrane affect the response to glucose, but the regulatory mechanism remains poorly understood. Here, we show that S-palmitoylation is required for stable plasma membrane enrichment of SGLT1 and for SGLT1-mediated GLP-1 secretion. Notably, myostatin (MSTN) was identified as a key upstream regulator of this modification. Intestinal MSTN deficiency markedly enhanced SGLT1 palmitoylation, increased its plasma membrane abundance, and thereby promoted glucose-stimulated GLP-1 secretion. Importantly, simvastatin induced intestinal MSTN upregulation and impaired glucose homeostasis, whereas MSTN deficiency largely alleviated these effects. Mechanistically, MSTN regulated the expression of the palmitoyl acyltransferase ZDHHC20, which catalyzed SGLT1 S-palmitoylation at Cys301. Blocking SGLT1 palmitoylation attenuated SGLT1 membrane enrichment and markedly suppressed the induction of GLP-1 secretion caused by MSTN deficiency. Collectively, our research results have revealed a new mechanism by which MSTN regulates intestinal endocrine function and S-palmitoylation modification promotes GLP-1 secretion, providing potential targets for regulating endogenous GLP-1 secretion in the intestine and treating metabolic diseases related to glucose imbalance.

PMID 42876031
Read full article →
PubMedFrontiers in pharmacology2026-10-14

Placental alkaline phosphatase promotes lipid accumulation and fibrosis in ligamentum flavum hypertrophy and represents a potential target for statin repurposing.

Cheng Junjie J, Hu Konghe K, Li Jianjun J, Lin Huanbin H et al.

Lumbar spinal stenosis is a prevalent degenerative disorder driven primarily by ligamentum flavum hypertrophy. Emerging evidence links ectopic lipid accumulation to fibrotic remodeling and suggests a potential contribution of immune dysregulation. However, the molecular targets connecting lipid accumulation with ligamentum flavum fibrosis remain incompletely defined. We sought to evaluate the underlying mechanisms of lipid-lowering drug targets in lipid-associated ligamentum flavum fibrosis. We applied two-sample Mendelian randomization (MR), summary-data-based MR, and Bayesian colocalization to evaluate the associations of genetically proxied levels of 213 lipid-lowering drug target proteins with lumbar spinal stenosis risk. Candidate targets were evaluated via genetic immune-cell mediation analysis, molecular docking, molecular dynamics simulations, and experimental validation in vitro and in vivo. MR identified three proteins increasing disease risk, with placental alkaline phosphatase (ALPP) consistently replicating across platforms (colocalization at rs12478529, PP.H4 = 0.9979). Genetically inferred mediation analysis suggested that selected immune-cell traits may partially mediate the association between ALPP and lumbar spinal stenosis. Molecular dynamics simulations and cellular thermal shift assays supported target engagement of atorvastatin and simvastatin with ALPP. In clinical specimens, ALPP was upregulated in hypertrophied tissues, co-localizing with fibrosis and lipid accumulation. In vitro, statins suppressed lipid accumulation and fibrotic markers; ALPP overexpression counteracted these protective effects. In vivo, systemic statin administration attenuated ligamentum flavum thickening, whereas local viral-mediated ALPP overexpression reversed this benefit. Our findings identify ALPP as a genetically supported candidate associated with LSS and link it to lipid accumulation and fibrosis. Computational and CETSA findings support possible target engagement of statins with ALPP and attenuate lipid accumulation and fibrosis, supporting ALPP as a potential mediator of their effects and statin repurposing for LSS.

PMID 42871036
Read full article →
PubMedBiomedical chromatography : BMC2026-10-13

Serum Pharmacochemistry and Metabolomics Reveal the Mechanism of Hedan Tablets Combined With Simvastatin in Hyperlipidemia Treatment.

Liu Shuo S, Zhang Yumeng Y, Dun Xiaoxu X, Zhang Jingxuan J et al.

Simvastatin (ST) is commonly used to treat hyperlipidemia (HLP), but it has serious side effects, such as myopathy and hepatotoxicity. Clinically, statins are often combined with Hedan tablets (HDT) to treat HLP, but the composition and mechanism of their pharmacological effects are still unclear. Therefore, the purpose of this study was to systematically explore the pharmacodynamic material basis and mechanism of HDT combined with ST in the treatment of HLP. Efficacy was assessed through serum lipid profiles and oxidative stress markers. The components entering the blood were identified by LC-MS. Metabolomic analyses were conducted using LC-MS and 1H-NMR techniques. Both single administration and combined administration have the effects of regulating blood lipids and oxidative stress, and the combination group showed significantly greater regulatory effects on TC, HDL-C, and GSH-Px than the simvastatin monotherapy group (p < 0.05). Twenty components were successfully identified in blood. Metabolomics revealed 61 significantly altered metabolites in the combination group, mapped to nine key metabolic pathways including glycerophospholipid metabolism and citrate cycle.

PMID 42866964
Read full article →
PubMedJournal of pharmaceutical sciences2026-10-11

Are we selecting the right model compounds for advanced formulation research?

Solymosi Tamás T, Kumar Dalip D, Urich JesúsAlbertoAfonso J, Hörmann-Kincses Theresa T et al.

Numerous advanced-formulation papers begin with the same problem statement: "30-40% of marketed drugs, 70-75% of clinical candidates and 90% of new chemical entities are poorly soluble in water". However, these figures are not fully supported by data and citations. We traced these numbers back to their original sources and reassessed them against the current API landscape. The 30-40% value was derived from a 2006 analysis of top selling drugs. Reassessing the top selling drugs in 2025 reveals a marked increase: about 55% of the orally administered small molecules now fall into the practically insoluble category. The 70-75% and 90% claims could only be traced to conference presentations and a review abstract with no underlying data. We further argue that the Biopharmaceutics Classification System categorization is not an intrinsic property of an API since it shifts depending on dose, particle size and formulation, i.e., no compound can be classified without considering the formulation and dose. A Scopus analysis showed that the APIs most frequently used as poorly soluble model compounds are the NSAIDs, antifungals and compounds, such as carbamazepine, carvedilol and simvastatin. The majority of these "poorly solubles" are in fact completely absorbed in vivo with no solubility issues at all. As more relevant alternatives to the above-mentioned compounds, we propose and briefly review ten marketed non-oncology APIs with unresolved dissolution and solubility limitations that would make better model compounds for advanced formulation research.

PMID 42858824
Read full article →
PubMedPloS one2026-10-09

Identification of flavonoids from natural products against hyperlipidaemia through computational approaches.

Mustaffar Kamal Nurnazira Hanis NH, Ismail Nurul Azira NA, Ali Ernie Zuraida EZ

Over the centuries, hyperlipidaemia has been recognised as a major risk factor contributing to cardiovascular disease (CVD). Current research increasingly explores natural compounds such as flavonoids for their potential lipid-lowering effects. This study evaluated pharmacological potential of flavonoids to identify strong inhibitors for target receptor, Proprotein Convertase Subtilisin/Kexin Type (PCSK9). A total of 29 compounds, including one FDA-approved drugs were screened for drug-likeness and ADMET properties, followed by molecular docking and Molecular Dynamics (MD) simulations using PCSK9 receptor containing glucose and sodium (PDB ID: 5OCA). This complex was chosen due to their functional relevance to cholesterol metabolism. As a results, 24 compounds satisfied Lipinski's Rule of Five and exhibited favourable drug-likeness and toxicity profiles. Simvastatin (control) was discovered to bind into the pocket B binding site along with seven flavonoids; Diosmetin, Eupatorin, Isorhamnetin, Myricetin, Petunidin, Sinensetin, and Tilianin. These flavonoids displayed docking energies ranging from -8.0 to -10.2 kcal/mol. Tilianin showed the strongest affinity (-10.2 kcal/mol), while Simvastatin bound with -9.1 kcal/mol. MD simulations confirmed that the PCSK9-ligand complexes remained structurally stable throughout a 100 ns trajectory. MM/PBSA analysis further supported the binding interactions, revealing free energies values ranging from -17 to -30.41 kcal/mol. Among the flavonoids evaluated, Tilianin, Myricetin, and Sinensetin demonstrate the most favourable interaction profiles. These finding suggest that the selected flavonoids have strong potential as promising anti-hyperlipidaemic candidates targeting PCSK9.

PMID 42853886
Read full article →
PubMedFolia morphologica2026-10-09

The combination of puerarin and simvastatin alleviates inflammatory responses and promotes osteogenic differentiation via an IRF4-mediated mechanism in periodontal ligament stem cells.

Lu Zhenfei Z, Lu Jin J, Zeng Bin B, Chen Liangjian L

The impaired function of periodontal ligament stem cells (PDLSCs) impedes the restoration of periodontal tissues. Puerarin (Pue) is a natural flavonoid component derived from Pueraria lobata, and simvastatin (Sim) is a lactone-form statin. Both have been shown to promote proliferation and osteogenic differentiation and to exert anti-inflammatory effects in human PDLSCs. This study aimed to elucidate the effects of Pue and Sim in lipopolysaccharide (LPS)-stimulated PDLSCs and the underlying mechanism. Bioinformatics, weighted gene coexpression network analysis (WGCNA), machine learning, and molecular docking were used to identify genes associated with periodontitis in the GSE10334 dataset. LPS was administered to simulate an inflammatory microenvironment in PDLSCs. IRF4 protein expression was assessed by western blotting. The mRNA levels of IRF4, RGS1, CD27, CXCR4, Runx2, ALP, and OCN were measured using quantitative real-time PCR. Cell viability was assessed using a Cell Counting Kit-8 (CCK-8) assay. The levels of lactate dehydrogenase (LDH), malondialdehyde (MDA), tumor necrosis factor-alpha (TNF-α), and interleukin-6 (IL-6) were measured using commercial kits or ELISA. Alkaline phosphatase (ALP) and Alizarin Red (AR) staining were performed to assess osteogenic differentiation. Diminished secretion of pro-inflammatory cytokines, reduced production of MDA and LDH, augmented ALP activity and calcium deposition, and elevated expression of osteogenic differentiation-related genes were observed in the Pue + Sim group compared with the Pue group, Sim group, and control group in LPS-treated PDLSCs. Bioinformatics, WGCNA, machine learning, and molecular docking identified IRF4 as a key gene associated with Pue and Sim treatment. The expression of IRF4 was significantly diminished following treatment with Pue, Sim, or Pue + Sim. The protective effect of Pue + Sim treatment was attenuated by IRF4 overexpression. The combination of Pue and Sim treatment showed strong effects in reducing inflammation and oxidative stress and promoting osteogenic differentiation via an IRF4-mediated mechanism in LPS-stimulated PDLSCs, providing a promising therapeutic strategy for treating periodontitis.

PMID 42851135
Read full article →

+9996 more articles available with a free account

Sign up free to view all articles →

Ask about simvastatin