PARP7 has been proven to play an important role in immunity. Substantial upregulation of PARP7 is observed in numerous cancerous cell types, consequently resulting in the inhibition of type Ⅰ interferon signaling pathways. Therefore, inhibiting the activity of PARP7 can enhance type Ⅰ interferon signaling to exert an anti-tumor immune response. In this study, we reported the identification of a newly found PARP7 inhibitor (XLY-1) with higher inhibitory activity (IC = 0.6 nM) than that of RBN-2397 (IC = 6.0 nM). Additionally, XYL-1 displayed weak inhibitory activity on PARP1 (IC > 1.0 μM). Mechanism studies showed that XYL-1 could enhance the type Ⅰ interferon signaling in vitro. Pharmacodynamic experiments showed that 50 mg/kg XYL-1 could significantly inhibit tumor growth (TGI: 76.5 %) and related experiments showed that XYL-1 could restore type Ⅰ interferon signaling and promote T cell infiltration in tumor tissues. Taken together, XYL-1 shows promise as a potential candidate for developing cancer immunotherapy agents.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.bioorg.2024.107469 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Inhibition of Abdominal Aortic Aneurysm Progression Through the CXCL12/CXCR4 Axis via MiR206-3p Sponge.
J Cell Mol Med
January 2025
Department of Vascular Surgery, The Second Hospital of Shanxi Medical University, Taiyuan, China.
Notably, the C-X-C Motif Chemokine Ligand 12/C-X-C Chemokine Receptor Type 4 (CXCL12/CXCR4) signalling pathway's activation is markedly increased in a mouse model of abdominal aortic aneurysms (AAA). Nonetheless, the precise contribution of this pathway to AAA development remains to be elucidated. The AAA mouse model was induced by local incubation with elastase and oral administration of β-aminopropionitrile.
View Article and Find Full Text PDFEfficient Production of Recombinant Human Brain-Derived Neurotrophic Factor in Through the Engineering of Its Pro-Region.
Int J Mol Sci
December 2024
Dompé Farmaceutici S.p.A., Via Campo di Pile, Nucleo Industriale Pile, 67100 L'Aquila, Italy.
Thus far, no manufacturing process able to support industrialization has been reported for the recombinant human brain-derived neurotrophic factor (rhBDNF). Here, we described the setup of a new protocol for its production in () and its purification to homogeneity. A synthetic gene, codifying for the neurotrophin precursor, was inserted into an expression vector and transformed into BL21 (DE3) strain.
View Article and Find Full Text PDFIntravenous injection of PCSK9 gain-of-function mutation in C57BL/6J background mice on Angiotensin II-induced AAA.
Biochim Biophys Acta Mol Basis Dis
January 2025
State Key Laboratory for Innovation and Transformation of Luobing Theory, Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese National Health Commission and Chinese Academy of Medical Sciences, Department of Cardiology, Qilu Hospital of Shandong University, Jinan, China. Electronic address:
Objective: This study was performed to compare the incidence of Angiotensin II (Ang II)-induced abdominal aortic aneurysms (AAA) between intravenous and intraperitoneal injection of AAV8.mPCSK9 in wild-type (WT) mice with C57BL/6J background and the pathological differences of above model in WT and ApoE mice.
Design: Male WT mice were injected intraperitoneally or intravenously with either a AAV8.
The outcome of late open conversion after endovascular abdominal aortic repair.
Asian Cardiovasc Thorac Ann
January 2025
Department of Cardiovascular Surgery, Chiba University Hospital, Chiba, Japan.
Background: Endovascular abdominal aneurysm repair (EVAR) offers a less invasive approach to treating abdominal aortic aneurysms (AAA) compared to open repair. However, EVAR is associated with higher rates of reintervention. This study investigates the early and mid-term outcomes of patients who underwent late open conversion including aneurysmorrhaphy after EVAR at our institution.
View Article and Find Full Text PDFTranscaval embolisation of type-II endoleaks - The Australian experience.
Vascular
January 2025
Department of Vascular and Endovascular Surgery, Townsville University Hospital, Townsville, QLD, Australia.
Objectives: Embolizing an abdominal aortic aneurysm sac through a transcaval approach is a novel approach to treat type-II endoleaks that occur following aortic endografting. This study reviews the outcomes of this treatment in one of the few centres in Australia that offers this procedure.
Methods: A retrospective cohort study was conducted, including patients who had received transcaval embolisation of type-II endoleak over a 9-year period.
Want AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!