sirolimus / Generic mfg. - LARVOL DELTA

Physiological Hypoxia and Pharmacological HIF Stabilization Induce Distinct but Overlapping Responses in Retinal Pigment Epithelial Cells. (PubMed, Pharmaceuticals (Basel)) - "Rapamycin inhibited VEGFA production only under physiological hypoxia, further supporting mechanistic differences between the two models. Functionally, conditioned media from hypoxic ARPE-19 cells promoted endothelial tube formation, which was significantly reduced by pathway inhibition. Collectively, these findings show that HIF-PHIs reproduce many, but not all, aspects of the physiological hypoxic response in RPE cells."

Journal • Chronic Kidney Disease • Hematological Disorders • Nephrology • Ophthalmology • Renal Disease • Retinal Disorders

Calcineurin Inhibitor-Based Triple Immunosuppressive Therapy Induces Profibrotic Changes in the Jejunal Mucosa of Male Rats: A Digital Image Analysis of Collagen Fibers. (PubMed, Biomedicines) - " Animals were treated for six months with regimens containing either cyclosporine A (CyA) or tacrolimus (TAC) in combination with rapamycin and prednisone. These findings suggest that long-term administration of CNI-based triple immunosuppressive therapy may be associated with changes consistent with fibrotic remodeling of the jejunal mucosa. The present study provides novel data on the effects of clinically relevant multidrug immunosuppressive protocols, whereas most previous experimental studies investigating the effects of immunosuppressive agents have focused on single-drug exposure in animal models or in vitro systems."

Journal • Preclinical • Fibrosis • Gastrointestinal Disorder • Solid Organ Transplantation • Transplantation

REDD1 Silencing Aggravates Aortic Dissection and Promotes VSMC Apoptosis with Autophagy-Related Changes. (PubMed, Biomedicines) - "REDD1 silencing in VSMCs increased BAX, p62 and p-mTOR while reducing BCL-2 and LC3B, accompanied by increased apoptosis and loss of mitochondrial membrane potential, whereas rapamycin reduced apoptosis and alleviated mitochondrial injury...Loss of REDD1 activity promotes mitochondrial injury and VSMC apoptosis, thereby aggravating AD. Targeting REDD1 may therefore represent a potential therapeutic strategy for AD."

IO biomarker • Journal • Cardiovascular • BAX • BCL2

Beyond Translation Initiation: Translational Elongation, Decoding Fidelity, and Ribosome Surveillance During Branched-Chain Amino Acid Deprivation, with a Focus on Mammalian Systems. (PubMed, Biology (Basel)) - "In mammalian systems, translational responses to amino acid limitation are commonly framed as mechanistic target of rapamycin complex 1 (mTORC1) inhibition and activation of the general control nonderepressible 2 (GCN2)-eukaryotic initiation factor 2α (eIF2α) arm of the integrated stress response...We propose a two-layer kinetic framework separating (i) A-site competition among correct decoding, substitution, and abortive exit from (ii) collision formation set by ribosome influx and dwell time. It keeps protein quantity, sequence fidelity, retained function, and proteostasis cost separate, and defines a matched measurement roadmap from metabolite flux to protein function."

Journal • Review • Oncology

A Novel Regulatory System in Brain Development and Death Driven by a Bioactive Peptide Linked to a Specific Isoform of Acetylcholinesterase. (PubMed, Biomolecules) - "We conclude that in development, T14 and AChE-R are closely linked, that both are involved in a developmental mechanism most active in the embryonic brain, and that inappropriate reactivation of this mechanism in the mature brain could be the driver in the progression of AD."

Journal • Alzheimer's Disease • CNS Disorders • Pain • ACHE

Two-Year Clinical Outcomes of Contemporary Drug-Eluting Stents Grouped by Eluted Limus Agent: A Retrospective Cohort Study. (PubMed, J Clin Med) - "We compared outcomes among contemporary sirolimus-, zotarolimus-, and everolimus-eluting stents. Because drug type is closely intertwined with stent platform design, these findings should not be extrapolated to individual stent platforms. The exploratory complex-PCI subgroup finding requires confirmation in larger studies."

Clinical data • Journal • Retrospective data • Cardiovascular • Myocardial Infarction

CREB1 and GSK3 Isoforms as Potential Adaptive Signaling Nodes in PI3K/Akt/mTOR Inhibitor Treated Philadelphia Chromosome-Positive B-ALL. (PubMed, Int J Mol Sci) - "Experimentally, phospho-kinase arrays profiled 39 kinase phosphorylation sites in Ph+ B-ALL cells (SUPB-15) treated with PI3K/Akt/mTOR inhibitors (Rapamycin, GDC-0941, GSK690693, Perifosine). These findings position p-CREB and p-GSK-3α/β as candidate biomarkers, highlighting the value of phospho-proteomics over transcriptomics alone in capturing pathway activation. Multi-omics integration may prove essential for overcoming adaptive resistance in ALL patients."

Journal • Acute Lymphocytic Leukemia • B Acute Lymphoblastic Leukemia • Hematological Malignancies • Leukemia • Oncology • ABL1 • BCR • CREB1

Integrated Proteomic Screening Reveals Heme Enzyme Depletion Induces Cyst-like Vacuole Formation in Toxoplasma gondii. (PubMed, Int J Mol Sci) - "Continuous fluorescence signals highlighted the parasitophorous vacuole (PV) membrane surrounding tachyzoites during both early and late replication stages, particularly at 48 h post-rapamycin treatment, indicating a transformation of the cyst-like PV resembling that in Toxoplasma gondii...However, this morphological change did not significantly affect the acute virulence of the parasites in vivo, as determined by mouse survival assays. This study explored the functional roles of the three intermediate metabolic enzymes, offering a novel viewpoint on the gradual demise of Toxoplasma gondii as a potential target for drug development."

Journal • UROD

Molecular Signaling Pathways, Regulatory and Coactivator Networks, and Emerging Mechanisms in Hepatocellular Carcinoma. (PubMed, Biomedicines) - "Molecular profiling studies have identified key oncogenic pathways involved in HCC progression, including MAPK/ERK (mitogen-activated protein kinase/extracellular signal-regulated kinase), Wnt/β-catenin, PI3K/AKT/mTOR (Phosphoinositide 3-kinase/Protein Kinase B/mechanistic Target of Rapamycin), Hippo-YAP/TAZ, (Yes-associated protein/transcriptional co-activator with PDZ-binding motif) cell cycle regulators, and p53-mediated tumor suppression...Additionally, recent bioinformatic analyses suggest a potential role for progesterone-mediated oocyte maturation pathways in HCC, although their functional relevance remains unclear. A thorough understanding of these interconnected mechanisms could lead to novel therapeutic targets and the development of more effective, personalized treatment strategies for HCC. This review discusses key signaling pathways and emerging mechanisms in HCC and their roles in disease development and treatment."

Journal • Review • Hepatocellular Cancer • Liver Cancer • Oncology • Solid Tumor • CTNNB1

The Role of Branched-Chain Amino Acids in Nutrient Allocation of the Porcine Placenta: A Review. (PubMed, Animals (Basel)) - "Branched-chain amino acids (BCAAs)-leucine, isoleucine, and valine-are substrates for protein synthesis, precursors for glutamate and glutathione, and signaling molecules that activate the mechanistic target of rapamycin (mTOR) pathway...Critical knowledge gaps remain, including the reliance on rodent and in vitro models, the absence of standardized supplementation protocols and dose-response data, unaddressed confounders (parity, litter size, environment), and the lack of formal power analyses or meta-analytic synthesis. We propose precision dietary strategies to optimize BCAA supplementation during gestation for improved reproductive performance in swine."

Journal • Preclinical • Review

Imatinib Mesylate and Sirolimus Inhibit Vascular Fibroproliferative Remodeling in Pulmonary Vein Stenosis. (PubMed, Children (Basel)) - " Fibroproliferative ECs undergoing EndMT are likely the cellular substrate underlying PVS development and progression. A multimodal approach consisting of anatomically focused surgical repair with adjunctive imatinib mesylate and sirolimus therapy may attenuate fibroproliferative remodeling."

Journal • Cardiovascular • Fibrosis • Heart Failure • Immunology

Sarcopenia and Skeletal Muscle Dysfunction in Liver Cirrhosis: Clinical Perspectives of Myostatin Inhibition. (PubMed, Biomedicines) - "Myostatin, in concert with downstream effectors such as mechanistic target of rapamycin (mTOR), plays a central role not only in skeletal muscle homeostasis but also in systemic metabolic regulation, highlighting its relevance beyond muscle biology alone...We critically evaluate existing and emerging myostatin-targeting approaches, including pharmacological inhibition and gene-based therapies, as potential strategies to restore muscle mass and function. Finally, we outline future directions for translational research aimed at modulating myostatin signalling in cirrhosis-associated sarcopenia, emphasising the need to elucidate its systemic metabolic effects to identify novel therapeutic targets and improve clinical outcomes in this population."

Journal • Review • Fibrosis • Gastroenterology • Gene Therapies • Hepatology • Immunology • Inflammation • Liver Cirrhosis • Liver Failure • Metabolic Disorders • Obesity • Sarcopenia • mTOR

Sirolimus Discontinuation Strategies in Kaposiform Hemangioendothelioma (clinicaltrials.gov) - P2 | N=120 | Recruiting | Sponsor: West China Hospital | Not yet recruiting ➔ Recruiting

Enrollment open • Oncology

Rapamycin modulates disease-relevant processes in the central nervous system of patients with early Alzheimer's disease: data from PET, MRI and CSF with long-term follow-up (CTAD 2026) - No abstract available

Clinical • Alzheimer's Disease • CNS Disorders

Kuwanon E sensitizes hepatocellular carcinoma cells to disulfidptosis via MTOR-mediated autophagy blockade. (PubMed, Biochem Pharmacol) - "Importantly, co-treatment with the MTOR inhibitor/autophagy inhibitor activator rapamycin or exogenous GSH supplementation effectively rescued KE-mediated disulfidptosis sensitization, confirming the functional centrality of MTOR signaling and GSH metabolism. These findings establish KE as a functional disulfidptosis-sensitizing agent from a natural source and provide a compelling mechanistic rationale for targeting disulfidptosis to overcome metabolic and autophagic resistance in HCC."

Journal • Hepatocellular Cancer • Oncology • Solid Tumor

mTORC1-TFEB/TFE3 signaling is associated with bile acid diversification during hepatic metabolic adaptation. (PubMed, Sci Adv) - "The mechanistic target of rapamycin complex 1 (mTORC1) integrates nutrient and hormonal cues to regulate hepatic lipid metabolism with major implications for metabolic dysfunction-associated steatotic liver disease (MASLD)...Furthermore, protein restriction (which inhibits mTORC1) similarly reshaped the BA profile in mice and correlated with improved metabolic outcomes in MASLD patients. Together, these findings uncover BA homeostasis as an integral component of the metabolic adaptations orchestrated by mTORC1, underscoring a link between nutrient signaling and metabolic liver disease."

Journal • Hepatology • Metabolic Disorders • Metabolic Dysfunction-Associated Steatotic Liver Disease • CYP8B1 • TFE3 • TFEB

Kinase crosstalk coordinates stress adaptation and metabolic homeostasis in plants. (PubMed, Planta) - "Central to these networks are mitogen-activated protein kinases (MAPKs), calcium-dependent protein kinases (CDPKs), sucrose non-fermenting-1-related kinases (SnRKs), and the Target of Rapamycin (TOR) complex, which collectively coordinate stress perception, metabolic regulation, and growth adaptation...Collectively, these interconnected kinase networks orchestrate survival strategies, metabolic homeostasis, and resilience under adverse conditions. By integrating these signaling modules into a systems-level framework, this review provides mechanistic insights and emerging perspectives for engineering crops with enhanced stress tolerance, growth stability, and energy-use efficiency."

Journal • Review

Intravenous sirolimus (albumin-bound HB1901) in malignant perivascular epithelioid cell tumors (PEComas): a multicenter, open-label, phase Ib/III trial update (ESMO 2026) - No abstract available

Clinical • Oncology

Refractory Tacrolimus Induced Autoimmune Hemolytic Anemia Requiring Sirolimus Conversion in a Liver Transplant Recipient (ACG 2026) - "Despite prednisone 120 mg daily, the patient remained transfusion-dependent, requiring daily to alternate-day pRBC transfusions with persistent hemoglobin < 7 g/dL and worsening hyperbilirubinemia. Weekly rituximab produced minimal response...Persistent hemolysis prompted escalation to IV methylprednisolone 200 mg daily. The clinical course was complicated by genital HSV infection requiring IV acyclovir...Danazol was added as adjunctive RBC maturation agent...In refractory cases, conversion from tacrolimus to sirolimus may restore immune balance through suppression of autoreactive B-cell and Th17 activity while maintaining graft function. This case highlights the importance of recognizing tacrolimus-associated warm AIHA and supports early consideration of sirolimus conversion in patients with refractory disease."

Clinical • Anemia • Autoimmune Hemolytic Anemia • Epstein-Barr Virus Infections • Fibrosis • Hematological Disorders • Hepatology • Herpes Simplex • Immunology • Infectious Disease • Inflammation • Metabolic Dysfunction-Associated Steatohepatitis • Respiratory Diseases • Transplant Rejection • Transplantation • HP

Single Doses of VTP-1000 Demonstrate Favorable Safety and Expected Pharmacokinetic and Pharmacodynamic Responses in Adults With Treated Celiac Disease (ACG 2026) - "The SAD portion of AVALON completed in September 2025 and MAD enrollment is ongoing. No treatment-related serious adverse events (AEs) occurred at any dose, and no treatment-related AEs greater than grade 2 were observed. Pharmacokinetic analyses indicate therapeutic rapamycin concentrations during antigen exposure and expected clearance."

Clinical • PK/PD data • Celiac Disease • Immunology • Inflammation • IL2

Late Acute Cellular Rejection Masquerading as Drug-Induced Liver Injury in a Liver Transplant Recipient With Recurrent Hepatocellular Carcinoma on the Graft (ACG 2026) - "Case Description/ A 74-year-old man with hepatitis C cirrhosis who achieved sustained virologic response in 2004, complicated by multifocal HCC, status post OLT in August 2023, with recurrent multifocal HCC within the graft treated with drug-eluting bead transarterial chemoembolization and cabozantinib while immunosuppression was transitioned from tacrolimus to sirolimus, presented to Hematology/Oncology (H/O) clinic with progressive weakness, poor oral intake, metallic taste, and refractory non-bloody diarrhea...Therefore, liver biopsy was crucial to establish a prompt diagnosis and provide appropriate treatment to preserve graft function and guide safe oncologic management. Figure: Figure 1: Liver biopsy (A) showing early changes of bile duct damage (yellow circles) and distortion of vein in the portal triad due to inflammation (red star); (B) showing endotheliitis favoring acute rejection (yellow arrow)."

Clinical • Acute Kidney Injury • Fibrosis • Hematological Disorders • Hepatitis C • Hepatocellular Cancer • Hepatology • Immunology • Infectious Disease • Liver Failure • Oncology • Solid Tumor • Transplant Rejection • Transplantation

An Uncommon Late Complication of Liver Transplantation: De Novo Metastatic Hepatic Malignancy (ACG 2026) - "He remains on chronic immunosuppressive therapy with oral sirolimus 1 mg daily...This case highlights that de novo primary liver malignancy can occur in long-term transplant recipients even without prior cirrhosis and may present with advanced metastatic disease requiring a high index of suspicion. Figure: H&E-stained image of sheets of neoplastic cells with polygonal eosinophilic cytoplasm, prominent nuclei, and surrounding liver parenchyma from the liver biopsy (10x) Figure: Positive CK7 immunohistochemical staining from the liver biopsy"

Metastases • Cardiovascular • Fibrosis • Hepatitis C • Hepatocellular Cancer • Hepatology • Immunology • Infectious Disease • Liver Cancer • Oncology • Pulmonary Embolism • Respiratory Diseases • Solid Tumor • Transplantation • CDX2 • GATA3 • NKX2-1

A Complicated Case of Granulomatous Hepatitis (ACG 2026) - "Ursodiol 500 mg BID was started in addition to her post-transplant immunosuppressive regimen of sirolimus, tacrolimus, and prednisone with subsequent LFT improvement. This case highlights the complexity of granulomatous hepatitis and underscores the critical role of liver biopsy in diagnosis, management, and identification of underlying etiologies. Figure: Figure 2: Representative trichrome stain showing stage 3-4 fibrosis"

Clinical • CNS Disorders • Fibrosis • Hepatitis C • Hepatology • Idiopathic Arthritis • Immunology • Inflammation • Inflammatory Arthritis • Liver Cirrhosis • Liver Failure • Primary Biliary Cholangitis • Primary Immunodeficiency • Pulmonary Disease • Respiratory Diseases • Rheumatoid Arthritis • Sarcoidosis

Intestinal Lymphangiectasia as a Cause of Acute Overt Gastrointestinal Bleeding: A Case Report (ACG 2026) - "Case Description/ A 70-year-old male with congenital protein-losing enteropathy, IL, prior jejunal resection (160 cm) for bleeding IL, chronic chylothorax (status post thoracic duct surgery and pleurodesis), and pulmonary emboli on apixaban presented with weakness, dyspnea, and near-syncope...Spironolactone was added for fluid retention...Additional therapeutic options include sirolimus, surgical resection, and lymphatic embolization. Dietary optimization and long-term iron supplementation remain cornerstones of care in IL with protein-losing enteropathy. Figure: Figure 1 and 2 Figure: Figure 3 and 4"

Case report • Clinical • Cardiovascular • Gastroenterology • Gastrointestinal Disorder • Pulmonary Disease • Pulmonary Embolism • Respiratory Diseases

Blue Rubber Bleb Nevus Syndrome Manifesting as Occult Gastrointestinal Bleeding (ACG 2026) - "Sirolimus is a potential treatment option that may reduce lesion size and risk of bleeding. Although rare, BRBNS is likely underrecognized and should be considered a differential for bleeding in both pediatric and adult populations. Figure: Capsule endoscopy images of small bowel"

Barrett Esophagus • Cardiovascular • Colorectal Cancer • Coronary Artery Disease • Gastroenterology • Gastroesophageal Reflux Disease • Gastrointestinal Disorder • Hematological Disorders • Rare Diseases • TEK