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

PubMedNeuropharmacology2026-09-03

Targeting the AMPK/SIRT1-NLRP3 Inflammasome Axis: Simvastatin, Ezetimibe, and Their Combination Attenuate 3-Nitropropionic Acid-Induced Striatal Neurodegeneration in Rats.

Rezqallah Abobakr M AM, Raafat Eman M EM, Nofal Shahira S

Striatal neurodegeneration, a prominent pathological feature of several neurological disorders, is associated with progressive behavioral decline alongside cognitive and motor dysfunction, reflecting the critical regulatory role of the striatum in coordinating multiple aspects of brain function. Neuroinflammation, particularly through NF-κB/NLRP3-pathway activation, which triggers the cleavage and subsequent secretion of IL-1β/IL-18, contributes substantially to neuronal injury, with glial activation serving as a key driver, whereas the AMPK/SIRT1-signaling cascade exerts anti-inflammatory and neuroprotective effects. Network pharmacology suggested potential interactions between AMPK/SIRT1-signaling and NF-κB/NLRP3-associated inflammatory and glial pathways. Simvastatin and Ezetimibe possess pleiotropic properties that may modulate these pathways. This research evaluated the neuroprotective potential of Simvastatin and Ezetimibe, given alone or combined, in a striatal neurodegeneration model induced by 3-nitropropionic acid(3-NP) in rats. Adult male Wistar rats were assigned by random selection into six-cohorts (n=15/group): control-cohort; 3-NP (10 mg/kg/day, administered intraperitoneally for 21 days) vehicle-cohort; and 3-NP-treated cohorts receiving Simvastatin (10 or 20 mg/kg, orally), Ezetimibe (10 mg/kg, orally), or a combination of both (10 mg/kg each). Treatments were administered 1h before 3-NP injection. Exposure to 3-NP induced marked oxidative stress, neuroinflammation, gliosis, neurotransmitter disturbances, histopathological alterations, and behavioral deficits. In comparison to the 3-NP-vehicle-cohort, Simvastatin and/or Ezetimibe enhanced AMPK/SIRT1-signaling, suppressed NF-κB/NLRP3 inflammasome activation, reduced glial reactivity, restored neurotransmitter homeostasis, and improved behavioral and histopathological outcomes. The combination regimen consistently produced the most pronounced protective effects. Collectively, Simvastatin and Ezetimibe attenuate 3-NP-induced striatal neurodegeneration, possibly through modulation of AMPK/SIRT1-associated neuroinflammatory and glial signaling pathways, warranting further evaluation in additional experimental models.

PMID 42692163
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PubMedFrontiers in immunology2026-09-03

Simvastatin as an immunomodulator and anti-myeloma agent - epidemiological, in vitro and murine model studies.

Lion Aharon A, Israel Arieh Y AY, Merzon Eugene E, Oster Howard H et al.

Simvastatin (SIM), a member of the statin family, is commonly used to lower blood cholesterol levels, particularly low-density lipoprotein. Statins inhibit the action of hydroxy-methyl-glutaryl-coenzyme A reductase, an important enzyme in the synthesis of cholesterol and isoprenoids; they also have anti-inflammatory effects and can regulate membrane synthesis in cancer cells. Preliminary evidence suggests an association between SIM use and reduced cancer incidence. SIM's anti-cancer efficacy in vivo has been shown in studies on several solid tumors, but little is known about its effects on hematological cancers, such as Multiple Myeloma (MM). Initially, we searched for such as an association in a large community database and observed a significantly lower MM incidence among SIM users. We proceeded to test the effect of SIM on both murine and human MM cell lines and the tested the effect of long-term SIM treatment on development of MM in an animal model. SIM exposure led to apoptosis in both murine and human MM cell lines. We show that long-term intake of SIM reduced tumor load and positively impacted bone marrow CD8+ T levels as well as cell-mediated anti-myeloma cytotoxicity. SIM treatment also elevated the total IgA and IgG serum concentrations in healthy mice. These results suggest that SIM, which many adults use to control cholesterol levels, may play a dual role in the management of MM, by influencing membrane synthesis in myeloma cells leading to apoptotic cell death and enhancing the T-cell mediated anti-tumor cell response in MM.

PMID 42688178
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PubMedClinical and translational science2026-09-03

A SHAP-Informed Formal Feature Attribution Framework for Drug-Drug Interaction Risk in Large-Scale Claims Data.

Dixon R Jerome RJ, Price Elvin T ET

Pairwise drug-drug interaction databases flag co-prescribed pairs, but they under-weight multi-drug combinations that drive adverse drug events in older adults. We studied that gap in Virginia All-Payer Claims Database records (2016-2019) for adults aged 65-114 years with non-opioid emergency department visits (n = 1182 cases; 16,105 matched controls across three geriatric age bands). Features came from pharmacy and medical claims in a short pre-index window optimized for acute ADE timing (21-30 days by age band; 21 days for ages 65-84). We trained gradient-boosting models separately among patients with similar pre-index healthcare contact volume (2016-2018 training; 2019 holdout), then used Formal Feature Attribution to score drug pairs and triplets and Intervention Rate ranks to order deprescribing review. On the 2019 holdout, geriatric AUPRC was 0.101-0.335 (PR lift 1.6×-4.2×). FFA flagged 115 synergistic pairs and 312 high-confidence triplets (e.g., furosemide + hydrochlorothiazide + lisinopril; digoxin + furosemide + amiodarone, IE = 8.7). Top Intervention Rate drugs included simvastatin, furosemide, and alprazolam. Moderate preventive Z-code monitoring (Q2) was protective (OR = 0.25; 95% CI 0.18-0.34) versus no monitoring, while fragmented high-intensity monitoring (Q4) was not. The framework prioritizes medication combinations for pharmacist review in claims data; it does not replace pharmacokinetic confirmation or prove that changing a drug caused fewer ED visits.

PMID 42687326
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PubMedJournal for immunotherapy of cancer2026-09-03

LIM and SH3 protein 1 deficiency confers resistance to cytotoxic lymphocyte-mediated lysis and immunotherapy in gastric cancer by disrupting cytoskeleton dynamics.

Zhang Teming T, Sun Yingying Y, Chen Chao C, Zheng Jingwei J et al.

A substantial amount of research has been dedicated to the mechanisms by which tumor cells evade immune system recognition and manipulate the immune microenvironment to facilitate immune escape. Recent studies have shown that viruses and tumors can protect themselves from immune cytotoxicity by remodeling the actin cytoskeleton. However, cytoskeleton-mediated immune resistance and the specific cytoskeleton-related proteins involved require further research. Single-cell RNA sequencing was used to identify cytoskeleton-related genes associated with the response to anti-programmed cell death protein 1 (PD-1) therapy across four digestive tumors. Immunohistochemistry was used to detect LASP1 expression in gastric cancer and analyze its prognostic value for survival and anti-PD-1 response. The impact of LASP1 deficiency on tumor response to anti-PD-1 treatment and cytotoxic lymphocyte-mediated lysis was determined in vivo and in vitro. Live-cell imaging was used to compare actin cytoskeletal dynamics at the immunological synapse between LASP1-deficient and mock tumor cells. Molecular mechanisms underlying LASP1-mediated immune-resistance were dissected using co-immunoprecipitation, immunofluorescence, domain deletion complementation, and Laurdan staining. The deficiency of LASP1 in gastric cancer affected the sensitivity of tumor cells to immunotherapy and induced cytotoxic lymphocytes exhaustion. LASP1 may act as a scaffold protein to regulate the Arp2/3 complex and remodel the cytoskeleton at the immunological synapses. LASP1 deficiency in tumor cells impairs lytic immunological synapse function by disrupting cytoskeletal dynamics-mediated cell membrane lipid organization at the immunological synapse. Finally, simvastatin combined with anti-PD-1 therapy reversed immunotherapy resistance in LASP1-deficient tumors. The deficiency of LASP1 in tumors mediates immunological synapse dysfunction by affecting cytoskeletal dynamics-mediated cell membrane lipid organization, thus enabling tumors to protect themselves from immune cytotoxicity and immunotherapy.

PMID 42686372
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PubMedZhongguo Zhong yao za zhi = Zhongguo zhongyao zazhi = China journal of Chinese materia medica2026-09-03

[Study on mechanism of Wendan Decoction in intervening in nonalcoholic fatty liver disease based on proteomics and network pharmacology].

Xiong Shu-Hua SH, Yan Jian-Min JM, Jiang Ruo-Nan RN, Zhang Meng-Ru MR et al.

This study systematically explored the molecular mechanism of Wendan Decoction(WDD) in treating nonalcoholic fatty liver disease(NAFLD) by integrating network pharmacology, proteomics, and experimental validation. A mouse NAFLD model was established using a high-fat diet, and the mice were randomly divided into a blank control group, a model group, a positive drug group(simvastatin, 3.03 mg·kg~(-1)), and low-(3.035 g·kg~(-1)), medium-(6.07 g·kg~(-1)), and high-dose(12.14 g·kg~(-1)) WDD groups, with intervention lasting for 6 weeks. After the intervention, the serum levels of alanine aminotransferase(ALT), aspartate aminotransferase(AST), triglycerides(TG), total cholesterol(TC), low-density lipoprotein cholesterol(LDL-C), and high-density lipoprotein cholesterol(HDL-C) were measured using an automatic biochemical analyzer. The serum levels of interleukin-1β(IL-1β), interleukin-6(IL-6), and tumor necrosis factor-α(TNF-α) were detected by ELISA. Liver histopathology was observed via hematoxylin-eosin(HE) staining and oil red O staining. Network pharmacology was used to predict potential targets and pathways, and proteomics was applied to identify differentially expressed proteins and related pathways. RT-qPCR and Western blot were performed to detect mRNA and protein expression of relevant genes. Animal experiments demonstrated that WDD dose-dependently ameliorated hepatic steatosis, inflammation, and lipid deposition, significantly reducing serum levels of ALT, AST, TG, TC, LDL-C, and pro-inflammatory cytokines(IL-1β, IL-6, and TNF-α), while significantly increasing serum HDL-C levels. Network pharmacology screening identified naringenin, baicalein, and other key active components, which were involved in pathways such as the peroxisome proliferator-activated receptor(PPAR), lipid, and atherosclerosis pathways. Proteomics further revealed differentially expressed pathways including the PPAR and advanced glycation end product-receptor(AGE-RAGE) signaling pathways. Integrated analysis highlighted the PPAR signaling pathway as the core mechanism. Molecular biology validation showed that WDD significantly regulated the mRNA expression of sterol regulatory element-binding protein-1c(SREBP-1c), fatty acid synthase(FASN), carnitine palmitoyl transferase 1A(CPT1A), acyl-CoA oxidase 1(ACOX1), and PPARα, as well as protein expression of PPARα, CPT1A, and PPARγ in mouse liver tissue. These results suggested that WDD might exert a multi-component, multi-target, and multi-pathway synergistic effect to improve lipid metabolism disorders and inflammatory responses with the PPAR signaling pathway as the central hub, thereby alleviating NAFLD progression.

PMID 42693063
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PubMedZhongguo Zhong yao za zhi = Zhongguo zhongyao zazhi = China journal of Chinese materia medica2026-09-03

[Mechanism of total saponins from Allium macrostemon in reducing inflammatory infiltration of aortic macrophages and anti-atherosclerosis in ApoE~(-/-) mice via regulating NF-κB signaling pathway].

Xu Ya-Nan YN, Lu Yi-Ting YT, He Sheng-Ping SP, Chen Xiang-Lian XL et al.

This paper aims to investigate the effects of total saponins from Allium macrostemon Bunge(SAMB) on aortic plaques and inflammatory infiltration macrophages in ApoE~(-/-) mice with atherosclerosis(AS). SAMB components were analyzed by ultra-performance liquid chromatography-quadrupole-time-of-flight mass spectrometry(UPLC-Q-TOF-MS). AS animal models were established by 50 ApoE~(-/-) mice fed with a high-fat diet and randomized into a model group, low-, medium-, and high-dose SAMB groups, and a simvastatin group. Ten C57BL/6J mice were selected as the control group. The mice in the blank group and model group were given normal saline by intragastric administration, and the remaining groups were administered corresponding drugs via gavage daily. Aortic sinuses were stained with hematoxylin and eosin(HE) to measure the ratio of aortic plaque area to luminal area. Aortic inflammatory factors such as tumor necrosis factor-α(TNF-α), interleukin-6(IL-6), monocyte chemoattractant protein-1(MCP-1), and interleukin-1β(IL-1β) were measured by enzyme-linked immunosorbent assay(ELISA). Macrophage infiltration areas were assessed by immunohistochemistry, and the protein expression levels of phosphorylated-nuclear factor-κB p65(p-NF-κB p65)/NF-κB p65 and inhibitor of nuclear factor α(IκBα) were assessed by Western blot. RAW264.7 macrophages were exposed to SAMB-containing serum with different concentrations. Proliferation ability was detected by EdU, and the migration ability of macrophages was detected by the wound healing assay and Transwell. The inflammatory factors, including TNF-α, IL-6, MCP-1, and IL-1β, were detected by ELISA; the levels of p-NF-κB p65/NF-κB p65 and IκBα were detected by Western blot; NF-κB p65 nuclear translocation was assessed by immunofluorescence. A total of thirty saponin components were identified from SAMB. Animal experiment results show that compared with the model group, low, medium, and high-dose SAMB groups significantly reduce aortic plaque area, aortic inflammatory factor levels, macrophage infiltration area, and protein expressions of p-NF-κB p65/NF-κB p65 in the vascular tissue of AS mice. Cell experimental results indicate that SAMB-containing serum can significantly inhibit LPS-induced abnormal proliferation and migration of RAW264.7 macrophages, reduce inflammatory factor release, decrease the levels of p-NF-κB p65/NF-κB p65 and IκBα, inhibit NF-κB p65 nuclear translocation, and block NF-κB signaling pathway activation. SAMB reduces inflammatory factors in vascular tissue of AS mice and inhibits macrophage infiltration in aortic plaques, exerting anti-atherosclerotic plaque formation effects. Its mechanism may be related to inhibiting the NF-κB-related pathway in macrophages.

PMID 42693027
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