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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)
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

PubMedNaunyn-Schmiedeberg's archives of pharmacology2026-07-24

Simvastatin enhances the antitumor activity of temsirolimus through AMPK-associated metabolic modulation in clear-cell renal cell carcinoma.

Chen Hsuan-Yu HY, Cheng Chien-Jui CJ, Hsu Te-Hsing TH, Tung Szu-Yu SY et al.

Clear-cell renal cell carcinoma (ccRCC) is characterized by VHL-associated metabolic reprogramming, including enhanced glycolysis and lipid biosynthesis, which may create therapeutic vulnerabilities. However, mTOR inhibitors such as temsirolimus often show limited efficacy due to adaptive metabolic compensation. We investigated whether simvastatin-induced metabolic stress enhances sensitivity to mTOR inhibition in a context-dependent manner in ccRCC. VHL-mutant (A498) and VHL-wild-type (Caki1) ccRCC cells were treated with simvastatin and temsirolimus, alone or in combination. Cell viability, colony formation, migration, Seahorse metabolic flux analysis, and Western blotting were performed. Mechanistic studies included shRNA-mediated knockdown of LKB1/AMPKα1/α2 and pharmacological modulation using Compound C and AICAR. Antitumor efficacy was evaluated in a Caki1 subcutaneous xenograft model in nude mice. Temsirolimus induced modest growth inhibition, whereas simvastatin produced stronger dose- and time-dependent effects. Combination treatment (simvastatin 2.5 µM + temsirolimus 100 nM) further reduced cell viability. Interaction analysis revealed a cell-dependent response, with synergism in A498 cells (combination index (CI), 0.31-0.77) and antagonistic-to-additive effects in Caki1 cells (CI, 1.6-2.7). Mechanistically, simvastatin activated LKB1-AMPK signaling, suppressed AKT/mTOR activity, reduced glycolysis (↓pPFKFB2), increased FBP1 expression, and downregulated lipid biosynthesis enzymes (FASN, SCD), thereby promoting ER stress and apoptosis. In vivo, combination therapy significantly suppressed tumor growth compared with monotherapy and alleviated temsirolimus-induced hypercholesterolemia without apparent toxicity. Simvastatin-induced metabolic perturbation enhances mTOR inhibition in a cell-dependent manner, supporting dual metabolic targeting as a potential therapeutic strategy in ccRCC.

PMID 42493660
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PubMedMetabolic engineering2026-07-24

Synthetic yeast-bacterium consortium enables co-inducible relayed synthesis of chemicals.

Xu Mingqiang M, Yu Jiahui J, Chen Xinjie X, Li Xie X et al.

Microbial coculture can integrate advantages and overcome the metabolic imbalance of individual species. Programming strain interactions represents a common routine for synthetic microbial communities with distinct species, which causes difficulties and redundant workloads in interaction construction before being available as chassis hosts. This study explores yeast-bacterium consortium without engineered interactions for the co-inducible relayed synthesis of natural products. The Komagataella phaffii-Escherichia coli consortium is explored for co-growth under selected conditions. Low-level glucose- and blue light-responsive transcriptional systems are rebuilt separately for each host, allowing single-signal co-induced activation of compound synthesis in coculture. Pathway redirection, genome mining, and rewiring of key targets for acyl donor degradation result in efficient production of the reporter molecule simvastatin (26.2 mg l-1) through living consortium cultured on simple carbon source. Inducible biosynthesis of another reporter compound (2S)-naringenin (165.6 mg l-1) further validates the extendibility of this community. The described platform represents a breakthrough in engineering microbial consortium for biosynthesis.

PMID 42492893
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PubMedAdvanced science (Weinheim, Baden-Wurttemberg, Germany)2026-07-23

AI-Assisted Engineering of Glycyrrhizic Acid/Simvastatin Nanocrystals for Multifunctional Treatment of Bacterial Osteomyelitis.

Han Yu Y, Zhao Yao Y, Yang Chengbo C, Niu Miao M et al.

Bacterial osteomyelitis remains a formidable challenge in clinic because existing monotherapies fail to block inevitable infection, uncontrolled inflammation, and impaired bone regeneration ‌concurrently. Here, we present an AI-assisted strategy that integrates antibacterial, anti-inflammatory, and pro-osteogenic activities into a single nanocrystal. Through machine learning‑assisted screening from FDA-approved active pharmaceutical ingredients (API), we identified glycyrrhizic acid and simvastatin as a multifunctional combination capable of self-assembling into uniform nanocrystals (SGNCs) with ultrahigh drug loading. SGNCs effectively neutralize reactive oxygen species, suppress M1 macrophage polarization, promote bactericidal effects, and reverse infection-impaired osteogenic differentiation. Mechanistically, RNA sequencing analysis further reveals that the beneficial effects of SGNCs are associated with the inhibition of inflammatory response via cytokine-cytokine receptor interaction pathway and the activation of bone regeneration program via the Wnt signaling pathway. As a consequence, SGNCs eradicate bacterial burden and restore bone microarchitecture with excellent biocompatibility in a rat osteomyelitis model. Our insights highlight an AI-assisted strategy that creates a mechanism-targeting nanomedicine solely from APIs for the efficient treatment of bacterial osteomyelitis, which currently requires multimodal management.

PMID 42490615
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PubMedPloS one2026-07-23

Platelet membrane biomimetic nanoparticle-based targeted delivery system of simvastatin for the treatment of ischemic stroke.

Li Qin Q, Li Rongyuan R, Lin Lu L, Gong Meiting M et al.

Blood-brain barrier (BBB) disruption and excessive neuroinflammation are pivotal drivers of cerebral ischemia-reperfusion injury. Although simvastatin (SV) possesses potent pleiotropic effects in promoting BBB repair and attenuating inflammation, its clinical translation for ischemic stroke is severely hampered by poor BBB penetration, low lesion accumulation, and the need for high systemic doses that increase the risk of off-target toxicity (e.g., myopathy). To address these barriers, herein, we developed a platelet membrane-biomimetic nanoparticle system (pmPLGA@SV) designed to leverage the innate affinity of platelets for injured vasculature for lesion-targeted SV delivery at a lower effective dose. Physicochemical characterization confirmed the successful cloaking of platelet membranes onto SV-loaded PLGA cores. In vitro, pmPLGA@SV demonstrated superior therapeutic versatility: it effectively scavenged reactive oxygen species in oxygen glucose deprivation/reoxygenation-treated PC12 cells and orchestrated microglial repolarization from a pro-inflammatory M1 phenotype toward an anti-inflammatory M2 state in BV2 cells, significantly modulating the secretion of IL-1β and IL-10. In vivo, pmPLGA@SV treatment dramatically reduced the cerebral infarct volume, exhibiting significant superiority over free SV. Furthermore, longitudinal behavioral assessments over 21 days demonstrated that pmPLGA@SV markedly accelerated motor and sensory-motor functional recovery, accompanied by consistent body weight regain and improved neurological scores. Mechanistically, pmPLGA@SV facilitates a synergistic therapeutic approach by mitigating neuronal oxidative stress and remodeling the inflammatory microenvironment. This study demonstrates that pmPLGA@SV serves as a robust biomimetic platform for the integrated treatment of neurovascular unit damage, offering a promising strategy for long-term neuroprotection and functional rehabilitation following ischemic stroke.

PMID 42490679
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PubMedNature communications2026-07-21

Statin-induced lipid carrier stress reveals a conserved vulnerability in β-lactam-resistant Gram-positive bacteria.

Torrens Gabriel G, Bisset Sean W SW, López-Bravo Maria M, Johansson Anders F AF et al.

Methicillin-resistant Staphylococcus aureus resists β-lactam antibiotics through the allosteric transpeptidase penicillin-binding protein 2a, which operates within staphyloxanthin-rich membrane microdomains. Statins restore susceptibility by disrupting these microdomains and impairing penicillin-binding protein 2a oligomerization, but the mechanisms enabling resistance to this resensitization remain unclear. Here we show, using evolution experiments in strains lacking a functional staphyloxanthin pathway, that mutations in gdpP, a regulator of cyclic di-adenosine monophosphate signaling, are the predominant route for restoring oxacillin resistance during membrane microdomain disruption. This adaptation is blocked by simvastatin, revealing a synthetic lethal interaction. Mechanistically, simvastatin inhibits the mevalonate pathway, depleting the essential lipid carrier undecaprenyl phosphate and exacerbating peptidoglycan precursor imbalance, an effect phenocopied by lipid carrier-targeting antibiotics such as bacitracin. Although compensatory mutations can restore resistance, they impose a fitness cost in vivo. Importantly, this vulnerability extends to Streptococcus pneumoniae, revealing a conserved strategy to overcome β-lactam resistance in Gram-positive pathogens.

PMID 42477355
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PubMedCancer chemotherapy and pharmacology2026-07-21

Drug repurposing as a promising therapeutic strategy against renal cell carcinoma.

Nakhaei Ali A, Taghavi Atefeh A, Aliyari Mahdieh M, Afshari Amir R AR et al.

Renal cell carcinoma (RCC) is a highly vascularized and metastatic malignancy of the kidney. The 5-year overall survival rate of RCC patients remains poor despite the development of therapeutic modalities. Therefore, identifying novel approaches to increase the sensitivity of RCC cells to drugs could help prolong patient survival. Recently, Drug repurposing, which leverages the established safety profiles and pharmacological properties of existing medications, has emerged as a promising alternative to traditional drug development. This approach can accelerate the translation of new therapies into clinical practice and is often associated with lower attrition rates in clinical trials. Recent evidence supports the therapeutic potential of various repurposed drugs against RCC. This review article summarizes and shows the effectiveness and potential of repurposed drugs including metabolic and cardiovascular modulators (metformin, simvastatin), antimicrobial and antiparasitic agents (artesunate, ivermectin, ketoconazole, chloroquine, hydroxychloroquine, niclosamide, doxycycline, pentamidine), mTOR inhibitors (temsirolimus, everolimus, rapamycin), anti-inflammatory and analgesic agents (aspirin, celecoxib), and agents with other mechanisms of action (acetazolamide, disulfiram). These agents exert their anticancer effects against RCC by modulating multiple signaling pathways, including PI3K/AKT/mTOR, AMPK, JAK2/STAT3, ERK1/2, Wnt/β-catenin, and RhoA/ROCK, as well as by inducing autophagy inhibition, ferroptosis, oxidative stress, and mitochondrial dysfunction, highlighting their utility in RCC therapy and emphasizing their clinical relevance.

PMID 42479152
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