sirolimus

P2, N=148, Recruiting, Odense University Hospital | Not yet recruiting --> Recruiting

Mechanistically, LGMN binds to integrin αvβ3 on the macrophage surface and restrains M1 polarization by inhibiting the mechanistic target of rapamycin complex 1 (mTORC1)/signal transducer and activator of transcription 1 (STAT1) pathway...These findings reveal the pivotal role of LGMN in restraining sarcoid granulomatous inflammation through suppression of mTORC1/STAT1-driven M1 macrophage polarization. Therefore, LGMN supplementation may be a promising therapeutic strategy for sarcoidosis.

Herein, through systematic screening of Jianwei Xiaoyan Granule (JWXYG)-derived compounds via molecular docking and surface plasmon resonance (SPR), we identified hederagenin as a potent and novel mechanistic target of rapamycin (mTOR) binder (Kd = 1.30 μM)...Importantly, mTOR knockdown abolished hederagenin-mediated LDHA suppression and compromised its therapeutic efficacy, validating mTOR as an essential target. Our findings demonstrated that hederagenin could inhibit inflammation-cancer transformation in CAG via regulation of glycolysis through the mTOR/HIF-1α pathway, which provided new candidate compounds for regulating the transformation of CAG into cancer.

This PROTAC nanoplatform is engineered by self-assembly of alkylated PROTAC prodrugs with human serum albumin (HSA) while simultaneously encapsulating the mTOR inhibitor rapamycin (RAPA) to inhibit extracellular PROTAC efflux...The efficacy of RAPA in overcoming PROTAC resistance was validated with multiple types of PROTACs, underscoring the generality of this approach. The coassembled nanoplatform integrating the alkylated PROTAC prodrug and RAPA highly efficiently suppressed tumor growth in a mouse model of PROTAC-resistant breast cancer.

We deployed our workflow to study schwannoma development and to test two clinically relevant drugs (rapamycin and brigatinib) head-to-head. Our results uncovered the very early onset of heterogeneity and macrophage recruitment to initiating schwannomas, and the unexpectedly distinct impacts of the two drugs on both, highlighting the value of the pipeline for rapid, innovative future drug-testing.

The discovery that the non-selective beta-blocker propranolol induces rapid regression of proliferating IHs established the first widely adopted systemic pharmacologic therapy in vascular anomaly care and provided a clinical proof-of-concept that targeting lesion-specific endothelial biology can alter disease course. In parallel, recurrent somatic variants affecting PI3K/AKT/mTOR (e.g., PIK3CA, TEK/TIE2, AKT1) and RAS/MAPK (e.g., KRAS, NRAS) signalling have reframed many malformations as mosaic disorders amenable to targeted inhibition with agents such as sirolimus, alpelisib, AKT inhibitors and MEK inhibitors. This review synthesizes translational mechanisms, clinical evidence and safety considerations for beta-blockers and emerging targeted therapies, emphasizing lesion phenotype, timing of intervention and molecular stratification as determinants of response. We highlight current limitations, including toxicity, durability and pathway escape, and outline future directions for precision therapy and genotype-guided trial design in vascular anomalies.

These processes suppressed mechanistic target of rapamycin kinase (mTOR) signaling, reduced OL-lineage cells, and caused hypomyelination. Restoring mTOR activity rescued OL maturation and improved social behavior in copper-deficient mice. These findings identify a copper-HIF1α-BNIP3-mTOR signaling axis that links trace element imbalance to glial dysfunction and ASD-relevant behavioral phenotypes, providing mechanistic insight into neurodevelopment.

GPR182+ PSCs could also predict the responses of colorectal cancer patients to certain drug treatments, such as rapamycin and midostaurin. Our findings map the epithelial heterogeneity in FAP and reveal that GPR182+ PSCs are crucial in driving heterogeneity and immune evasion. GPR182+ PSCs represent promising biomarkers for prognosis and drug responses, providing novel insights into FAP pathology and therapeutic development.

Mechanistic target of rapamycin (mTOR) signaling is mediated through mTORC1 and mTORC2...Manipulating mTORC1 and mTORC2 signaling produced both overlapping and distinct effects on neuronal structure - in some cases offsetting changes associated with epilepsy, but in most cases producing similar effects in healthy and epileptic animals. Findings provide new insights into the role of mTOR signaling in epilepsy, and guidance for predicting off target effects of mTOR antagonism.

The study demonstrated that COL11A1 exerts its oncogenic effects by suppressing autophagy via the AKT/Beclin 1 pathway, consequently inhibiting ferroptosis in pancreatic cancer cells. These findings reveal a novel molecular mechanism through which COL11A1 promotes tumor progression and provide a potential therapeutic target for pancreatic cancer treatment.

P2, N=59, Completed, City of Hope Medical Center | Active, not recruiting --> Completed | Trial completion date: Jan 2026 --> Oct 2025

P1/2, N=49, Recruiting, Fundacion Publica Andaluza Para La Gestion De La Investigacion En Salud De Sevilla | Not yet recruiting --> Recruiting