Tag: Enzyme Kinetics and Mechanisms
[ASAP] Photocatalytic Substrate Oxidation Catalyzed by a Ruthenium(II) Complex with a Phenazine Moiety as the Active Site Using Dioxygen as a Terminal Oxidant
YAP enhances mitochondrial OXPHOS in tumor-infiltrating Treg through upregulating Lars2 on stiff matrix
Background Tumor-infiltrating regulatory T cells (TI-Tregs) are well-adapted to thrive in the challenging tumor microenvironment (TME) by undergoing metabolic reprogramming, notably shifting from glycolysis to mitochondrial oxidative phosphorylation (OXPHOS) for energy production. The extracellular matrix is an important component of the TME, contributing to the regulation of both tumor and immune cell metabolism patterns by… Continue reading YAP enhances mitochondrial OXPHOS in tumor-infiltrating Treg through upregulating Lars2 on stiff matrix
[ASAP] Disappearance of Odd–Even Effects at the Substrate Interface of n-Alkanes
PD-L1 Expression for Tailoring Treatment in Advanced Melanoma—It Is Never That Easy—Reply
In Reply We appreciate the thoughtful comments to this Viewpoint by Karahan et al that emphasize the importance of considering additional predictive parameters when determining immunotherapy treatment strategies for patients with advanced melanoma. In patients with treatment-naive unresectable or metastatic melanoma and no central nervous system metastases, various clinical and molecular biomarkers, including programmed cell… Continue reading PD-L1 Expression for Tailoring Treatment in Advanced Melanoma—It Is Never That Easy—Reply
3-Thio-3,4,5-Trisubstituted-1,2,4-Triazoles: High Affinity Somatostatin Receptor-4 Agonist Synthesis and Structure-Activity Relationships
Somatostatin receptor-4 (SST4) is a therapeutic target for several conditions, including Alzheimer’s disease, seizures, neuropsychiatric disorders, and pain. Our previous work on 1,2,4-triazole derivatives led to enhanced SST4 binding affinity, selectivity, and functional activity. Herein we report the discovery of 3-thio-1,2,4-triazole series as selective and high affinity SST4 agonists. Thirty-three compounds show 300-fold selectivity over… Continue reading 3-Thio-3,4,5-Trisubstituted-1,2,4-Triazoles: High Affinity Somatostatin Receptor-4 Agonist Synthesis and Structure-Activity Relationships
1504 Primary analysis of the registration-intended cohort of patients with anti-PD-1-failed melanoma from the IGNYTE trial of RP1 plus nivolumab, including clinical subgroup and initial biomarker data
Background Patients with advanced melanoma progressing on anti–PD-1 therapy have limited and toxic treatment options. RP1 (vusolimogene oderparepvec) is an HSV-1–based oncolytic immunotherapy expressing GM-CSF and a fusogenic glycoprotein (GALV-GP-R–). The registration-intended cohort from the IGNYTE trial tested RP1 combined with nivolumab in melanoma patients with confirmed progression while being treated with anti–PD-1 mono- or… Continue reading 1504 Primary analysis of the registration-intended cohort of patients with anti-PD-1-failed melanoma from the IGNYTE trial of RP1 plus nivolumab, including clinical subgroup and initial biomarker data
1452 Livmoniplamab dose selection for dose optimization in patients with solid tumors to address project optimus: application of translational approach and pharmacokinetic-pharmacodynamic modeling
Background Livmoniplimab is an IgG4 that targets the glycoprotein-A repetitions predominant-transforming growth factor (GARP-TGF)-β complex, blocking release of active TGF-β1 and facilitating anti-tumor immune response. It is being investigated in combination with budigalimab (anti-PD-1) in patients with solid tumors. To address Project Optimus, we characterized the pharmacokinetics and preclinical and clinical PK/PD relationships to identify… Continue reading 1452 Livmoniplamab dose selection for dose optimization in patients with solid tumors to address project optimus: application of translational approach and pharmacokinetic-pharmacodynamic modeling
1355 AGEN1721, a first-in-class Fc-enhanced bifunctional antibody targeting FAP and TGF{beta}, remodels the tumor microenvironment to overcome cancer-associated fibroblast-mediated immune suppression
Background Cancer associated fibroblasts (CAFs) are a critical pro-tumorigenic and immunosuppressive cell subset within the tumor microenvironment (TME) that promotes resistance to immune checkpoint inhibitors. Enrichment of fibroblast activation protein (FAP)-expressing CAFs correlates with poor immunotherapy response across multiple cancer types, identifying these cells as potential drivers of resistance. TGFβ, produced by both tumor and… Continue reading 1355 AGEN1721, a first-in-class Fc-enhanced bifunctional antibody targeting FAP and TGF{beta}, remodels the tumor microenvironment to overcome cancer-associated fibroblast-mediated immune suppression
1426 The anti-tumor activity of a novel anti-Her2/anti-Trop2 bispecific VHH antibody-drug conjugate (ADC)
Background Her2 and Trop2, two tumor-associated antigens (TAAs), are well-established cancer targets validated by the approval of several anti-Her2 ADCs and an anti-Trop2 ADC. Her2 and Trop2 are expressed separately or co-expressed in cancer cells within tumors, reflecting the heterogeneity of tumor TAA expression. Currently, there is no approved bispecific ADC that targets both Her2… Continue reading 1426 The anti-tumor activity of a novel anti-Her2/anti-Trop2 bispecific VHH antibody-drug conjugate (ADC)