IR (Insulin receptor)

In this study, we investigated the effects of simvastatin, atorvastatin and rosuvastatin in BC cells stimulated by insulin. Consistent with these findings, survival analyses of large cohorts of patients revealed that high levels of NUPR1 are associated with poor BC prognosis. Overall, our results provide novel mechanistic evidence supporting the repositioning of statins in BC, particularly in tumors characterized by elevated IR expression and activity.

Additionally, we developed a practical all-protein mutIGF-II LYTAC by genetically encoding mutIGF-II into a mammalian expression vector and transfecting it into cancer-relevant cell lines. The secreted mutIGF-II-based PD-L1 degrader effectively induced PD-L1 degradation.

P3, N=315, Active, not recruiting, Amgen | Recruiting --> Active, not recruiting | N=927 --> 315

Conversely, pharmacological inhibition of mTORC1 or genetic ablation of Irtks ameliorates hepatic steatosis, inflammation, and metabolic dysfunction in mouse models. Our study establishes IRTKS as a central regulator of mTORC1-dependent metabolic reprogramming during hepatocarcinogenesis, providing potential therapeutic targets for MASLD-associated liver cancer.

Protective filters for the skin, such as those used for UVR radiation, are not available for IR and visible light. The use of creams containing antioxidants or iron oxide pigments could offer some protection in these spectral ranges.

Additionally, DMB reduced levels of AD-related biomarkers, including BACE-1 (β-secretase 1), amyloid-β, and acetylcholinesterase, indicating its capacity to mitigate oxidative stress and amyloidogenesis. This multidisciplinary approach, integrating in vivo and in-silico methodologies, provides a comprehensive understanding of DMB's neuroprotective effects and underscores its potential as a therapeutic agent for both AD and diabetes.

To our knowledge, this is the first demonstration of IR-A protein expression. Thus, IR-A mRNA and protein expression demonstrate a potential role for this insulin receptor isoform in breast cancer biology.

However, there were no differences in PTC characteristics between groups with varying degrees of IR. Mechanisms linking severe IR with PTC development require further investigation.

Additionally, suppressing AKT1 expression diminished the impact of INSR on promoting AML cells proliferation, invasion, and migration. This study indicates that INSR expression is elevated in AML cells after treating with chidamide and that INSR promotes AML cells proliferation and migration by upregulating AKT1 expression.

This disruption results in enhanced accumulation of protein aggregates, increased protein polyubiquitination, endoplasmic reticulum stress, and activation of apoptotic pathways. Collectively, our findings support the repurposing of ceritinib in combination with carfilzomib as a translationally relevant and safe strategy to circumvent PI resistance in MM, warranting further clinical investigation in the relapsed/refractory disease setting.

A newly identified bioactive compound gymnemantoside A, isolated from Gymnema inodorum, was structurally characterized and showed efficacy in Dex-induced muscle atrophy models. Gymnemantoside A produces anti-muscle atrophy effects by a hitherto unreported mechanism: modulation of the insulin receptor kinase domain and activation of downstream signalling, alongside competitive inhibition of the glucocorticoid receptor, which has been implicated in multiple forms of skeletal muscle wasting.

Here, we applied our recently developed single-cell lineage tracing method ReSisTrace to identify cells that are intrinsically resistant or sensitive to the FLT3 inhibitors midostaurin and quizartinib in AML with FLT3-ITD mutations...In addition, in an FLT3-ITD-positive AML patient-derived xenograft (PDX) mouse model, the CC-90009 and quizartinib combination showed significantly higher anti-tumor efficacy and prolonged overall survival compared to either treatment alone...Vistusertib (mTOR inhibitor), linsitinib (IGF1R and insulin receptor inhibitor), and meisoindigo (IGF1R and Src family kinase inhibitor), all inhibiting pathways parallel to or downstream of oncogenic FLT3 signaling, were predicted and validated to sensitize FLT3-mutated cell lines and primary cells to FLT3 inhibitors. Collectively, these findings demonstrate the ability of ReSisTrace to unveil pre-existing transcriptional features of treatment vulnerability in hematological cancers and elucidate strategies for enhancing FLT3 inhibitor treatment efficacy in FLT3-ITD-mutated AML.