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sirolimus (Excel / Excel II)

✓ Approved

JW Medical Systems · MTOR · Small Molecule

What is sirolimus?

sirolimus is a small molecule developed by JW Medical Systems. It is approved for therapeutic indications via surgical implantation.

Drug Profile

Brand NamesExcel, Excel II
CompanyJW Medical Systems
Drug ClassSmall Molecule
Molecular TargetMTOR
RouteSurgical Implantation
StatusApproved
Sources: ClinicalTrials.gov, JW Medical Systems

Mechanism of Action

Molecular Targets

sirolimus acts on 1 molecular target:

MTORmechanistic target of rapamycin kinase (FRAP2, RAPT1)
Want deeper analysis?Noah AI can explain complex mechanisms and compare to similar drugs.

Therapeutic Indications

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

Therapeutic AreaConditionPhase
Injury, poisoning and procedural complicationsRestenosis✓ Approved

Related Research Articles

PubMedFrontiers in cardiovascular medicine2026-11-12

Case Report: Shifting the paradigm in refractory in-stent restenosis: systemic immunomodulation with hydroxychloroquine and sirolimus.

Liao Jiangquan J, Wang Yan Y, Zhang Jie J, Xie Tianshu T et al.

Recurrent in-stent restenosis (ISR) refractory to repeated percutaneous interventions remains a formidable clinical challenge. Despite the established efficacy of drug-coated balloons (DCBs) and drug-eluting stents, a subset of patients experience relentless restenosis, highlighting the need for novel systemic strategies targeting underlying pathophysiological drivers. To describe a case of extreme, refractory recurrent ISR that failed multiple DCB interventions but was associated with a marked response to systemic therapy with Hydroxychloroquine (HCQ) and Sirolimus, and to discuss the mechanistic rationale and potential clinical implications. A 56-year-old female presented with rapidly recurring ISR in both the left anterior descending (LAD) and right coronary arteries (RCA). Over a 6-year period, she underwent 11 interventional procedures at our center and at outside institutions. Sequential trials of oral anti-inflammatory agents failed to halt the restenosis cycle. In May 2023, HCQ was initiated, and Sirolimus was added in October 2023. Serial angiographic and intravascular ultrasound (IVUS) follow-up were performed. Prior to systemic therapy, restenosis occurred every 6 months in both vessels. After initiating HCQ and Sirolimus, the RCA remained free of restenosis for over one year. The LAD, while requiring additional focal DCB treatments, showed a marked reduction in restenosis burden, with disease becoming highly localized. IVUS revealed neointimal hyperplasia with superimposed lipid-rich and fibrous plaques, without evidence of stent fracture or malapposition. In a patient with recurrent ISR, targeted systemic immunomodulation with HCQ and Sirolimus was associated with sustained vessel patency and reduced restenosis burden. This case provides a hypothesis-generating observation that addressing systemic inflammatory and proliferative drivers may repersent a potential salvage strategy for refractory recurrent ISR, warranting further prospective investigation.

PMID 43017047
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PubMedJournal of mass spectrometry and advances in the clinical lab2026-11-11

Preliminary Analytical Evaluation of the Automated Cobas i601 LC-MS/MS System for Immunosuppressant Quantification in a Clinical Laboratory.

Serres-Gómez Mariana M, Gemma Serrano Olmedo María M, Luisa González-Casaus María M, Fernández-Puntero Belén B et al.

Therapeutic drug monitoring (TDM) of immunosuppressive drugs is essential to maintain concentrations within narrow therapeutic windows and minimize toxicity. Automated liquid chromatography-tandem mass spectrometry (LC-MS/MS) platforms can combine the analytical specificity of mass spectrometry with workflow efficiency suitable for routine laboratories. To preliminarily evaluate the analytical performance of the Cobas i601 automated LC-MS/MS system for quantifying tacrolimus, cyclosporine, everolimus, and sirolimus and to compare results with routine immunoassays and an LC-MS/MS method for sirolimus. Imprecision, bias, and linearity were assessed according to the Clinical Laboratory Standards Institute (CLSI) EP10-A3 standard using quality-control materials. Method comparison and bias estimation versus the Dimension EXL 200 immunoassays and an LC-MS/MS technique for sirolimus followed the CLSI EP09-A3 standard. Regression analyses and predicted biases at therapeutic range concentrations were compared with allowable limits. The Cobas i601 showed good precision and linearity, meeting manufacturer specifications. The highest coefficients of variations for tacrolimus, everolimus, cyclosporine, and sirolimus were 4.0%, 4.7%, 3.6%, and 4.8%, and the maximum EP10-A3 biases were -7.4%, -3.9%, 4.7%, and 5.4%, respectively. In the method comparison, tacrolimus, everolimus, and cyclosporine showed substantial negative biases versus immunoassays (-22.7%, -38.9%, and -37.5%), exceeding allowable limits. Sirolimus exhibited smaller positive bias relative to the LC-MS/MS method (12.5%). Interchangeability between the methodologies cannot be assumed. The Cobas i601 provides reliable automated LC-MS/MS quantification of immunosuppressants, with good precision and linearity. Method-dependent biases highlight the need for careful interpretation during technology transitions. The Cobas i601 shows strong potential for routine LC-MS/MS implementation in TDM in clinical laboratories.

PMID 43011875
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PubMedBiological & pharmaceutical bulletin2026-11-11

Preclinical Evaluation of Effects of KP-001, a Selective Phosphatidylinositol 3-Kinase Alpha (PI3Kα) Inhibitor, on Human Immune Cell Function in Comparison with Existing Drugs for Refractory Vascular Malformations.

Kato Daiki D, Koyama Erika E

Vascular malformations (VMs) are morphogenesis defects of blood and lymphatic vessels, and excessive activation of the phosphatidylinositol 3-kinase (PI3K)/protein kinase B/mammalian target of rapamycin (mTOR) pathway via PI3Kα contributes to their pathogenesis. Sirolimus (an mTOR inhibitor used for the treatment of VMs in Japan) poses immunosuppression-related infection risks resulting from the blockade of signaling downstream of the PI3Kδ pathway. In this study, the human PI3K isoform inhibitory activity of KP-001 (a PI3Kα inhibitor currently in a Phase 3 trial for treating refractory VMs in Japan) was compared with that of alpelisib (a PI3Kα inhibitor for treating PIK3CA-related overgrowth spectrum in the United States). Additionally, we compared the inhibitory effects of KP-001 with those of sirolimus and alpelisib on human immune cells in vitro. KP-001 showed selective inhibitory activity against PI3Kα, including its mutant forms, and approximately 8-fold higher selectivity for PI3Kα over PI3Kδ than alpelisib. The IC50 of KP-001 for human T-cell proliferation and immunoglobulin G (IgG) production in human B cells was the highest among the test substances. Furthermore, compared with sirolimus and alpelisib, KP-001 demonstrated greater separation (IC50/Cmax ss, free ratio) between the IC50 for T-cell proliferation or B-cell IgG production and the effective plasma concentration in clinical settings (Cmax ss, free), estimated as the maximum plasma-free concentration of the test substance at steady state at the clinical dose. KP-001 may represent a beneficial treatment option for refractory VMs, with less immunological impact, owing to its superior PI3Kα selectivity and higher IC50/Cmax ss, free ratio than those of existing drugs.

PMID 43014707
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PubMedJournal of the American Academy of Dermatology2026-11-10

Topical sirolimus gel for hyperplastic rosacea: A randomized, double-blind, controlled study and exploration of two-dimensional to three-dimensional approximate protrusion volume (APV) assessment.

Xu Bingyang B, Chen Hao H, Chu Jiali J, Wang Yuanqin Y et al.

Hyperplastic rosacea is difficult to treat. Sirolimus may be a topical option. To evaluate topical sirolimus gel and explore two-dimensional-to-three-dimensional approximate protrusion volume (APV) assessment. In this randomized, double-blind, placebo-controlled trial, 65 patients applied 0.2% sirolimus gel (n = 29) or placebo (n = 36) twice daily. The primary endpoint was an Investigator's Global Assessment (IGA) score ≤1 after a 12-week cycle. Secondary and exploratory endpoints included Clinician's Erythema Assessment (CEA) success, artificial intelligence-estimated APV change, subgroup analyses, and correlations between APV and clinical scores. IGA success was 72.4% versus 33.3% (adjusted relative risk, 1.949; 95% confidence interval [CI], 1.153-3.294; P = .013), and CEA success was 69.0% versus 30.6% (adjusted relative risk, 2.778; 95% CI, 1.627-4.743; P < .001). APV reduction was greater with sirolimus (-61.556 units; P < .001). Baseline APV correlated with IGA (ρ = 0.386; P = .001) and CEA (ρ = 0.314; P = .011). No serious adverse events occurred. Single-center design, small sample, short follow-up, unvalidated algorithm, and no systemic absorption, quality-of-life, or satisfaction assessments. Topical sirolimus gel showed exploratory clinical and APV signals; confirmatory trials are needed.

PMID 43007256
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PubMedJournal of medical case reports2026-11-10

Delayed diagnosis of tuberous sclerosis complex in a young adult with long-term refractory epilepsy: a case report.

Zhao Dapeng D, Yu Ailing A, Chang Yanyan Y, Xu Linying L et al.

Tuberous sclerosis complex (TSC) is a rare autosomal dominant neurocutaneous hamartomatous disorder characterized by widespread multi-system hamartomatous lesions, with epilepsy occurring in the majority of affected patients. When refractory epilepsy serves as the sole long-standing clinical manifestation, subtle cutaneous and radiological hallmarks are easily overlooked, inevitably leading to diagnostic delay. We herein report a 23-year-old female patient presenting with a decade-long history of drug-refractory seizures. Physical examination revealed mild cognitive impairment with a Mini-Mental State Examination (MMSE) score of 22 (technical secondary school education) and no focal neurological deficits. A typical lumbosacral shagreen patch and a surgical scar from prior great toe periungual fibroma resection were identified on cutaneous inspection. Brain MRI demonstrated white matter migration lines on fluid-attenuated inversion recovery (FLAIR) sequences, while cranial CT detected subependymal calcified nodules. Sanger genetic sequencing confirmed a heterozygous pathogenic splice-site variant NM_000368.5:c.107-2A > G in the TSC1. Given her childbearing potential, valproate was gradually tapered and substituted with lamotrigine to minimize teratogenic risks. Sirolimus-mediated mTOR-targeted therapy was initiated alongside renoprotective agents and regular serial imaging surveillance. Optimized combination therapy yielded a remarkable reduction in seizure frequency during follow-up. TSC may manifest insidiously for years with refractory epilepsy as its only prominent clinical feature. Comprehensive screening consisting of thorough cutaneous examination, standardized cranial imaging and molecular genetic testing is mandatory for early identification of this disorder. Individualized antiseizure regimens combined with mechanistic target of rapamycin (mTOR) inhibitors can significantly improve seizure control and long-term clinical outcomes in TSC patients.

PMID 43004460
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PubMedOrphanet journal of rare diseases2026-11-06

Long-term treatment with sirolimus for pediatric vascular anomalies.

Park Jueun J, Kwon Hyunhee H, Kim Dae Yeon DY, Kim Seong Chul SC et al.

Although sirolimus has emerged as a safe and effective treatment modality for unresectable vascular anomalies, comprehensive long-term follow-up data remain scarce in the current literature. This study aims to evaluate the long-term clinical experience of pediatric patients with vascular anomalies who received sirolimus treatment over five years. We retrospectively analysed 17 pediatric patients with vascular anomalies treated with sirolimus over five years in Asan Medical Center. Lesion volumes were measured via 3D volumetric MRI and normalized to body surface area (BSA). Adverse drug effects and therapeutic responses were periodically assessed. Longitudinal response was modeled using generalized additive mixed-effects models (GAMM). Tapering protocols were initiated after 24 months of stability, and alpelisib switch was considered for sirolimus-refractory cases with documented PIK3CA mutations. With a median follow-up of 78 months, the overall response rate was 81.3%. GAMM analysis demonstrated a significant non-linear volume reduction (p < 0.0001), characterized by a rapid initial response within 12-24 months followed by a sustained plateau. Tapering was successful in 70.6% of patients without disease progression. Three patients with suboptimal responses transitioned to alpelisib; those with sufficient follow-up achieved additional volume reduction within 12 months. Long-term sirolimus use was well-tolerated, with no Grade ≥ 3 adverse events reported. Sirolimus provides sustained long-term efficacy and safety in pediatric vascular anomalies. The observed treatment plateau suggests that dose tapering is a viable strategy for sustained responders. Furthermore, genotype-guided transition to alpelisib offers an effective alternative for refractory PIK3CA-mutant cases.

PMID 42989251
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