AbstractThe Duffy‐binding protein (DBP) is a promising antigen for a malaria vaccine that would protect against clinical symptoms caused by Plasmodium vivax infection. Region II of DBP (DBP‐II) contains the receptor‐binding domain that engages host red blood cells, but DBP‐II vaccines elicit many non‐neutralizing antibodies that bind distal to the receptor‐binding surface. Here, we engineered a truncated DBP‐II immunogen that focuses the immune response to the receptor‐binding surface. This immunogen contains the receptor‐binding subdomain S1S2 and lacks the immunodominant subdomain S3. Structure‐based computational design of S1S2 identified combinatorial amino acid changes that stabilized the isolated S1S2 without perturbing neutralizing epitopes. This immunogen elicited DBP‐II‐specific antibodies in immunized mice that were significantly enriched for blocking activity compared to the native DBP‐II antigen. This generalizable design process successfully stabilized an integral core fragment of a protein and focused the immune response to desired epitopes to create a promising new antigen for malaria vaccine development.

01 Feb 2024·Phytotherapy Research

Icariside II prevents kidney fibrosis development in chronic kidney disease by promoting fatty acid oxidation

Article

Author: Qian, Yiling ; Wang, Meng ; Wang, Lingchen ; Feng, Xiaoxuan ; Ye, Chaoyang ; Wang, Jing ; Wang, Chen

AbstractRenal interstitial fibrosis (RIF) is the main pathological basis for the progression of chronic kidney disease (CKD), however, effective interventions are limited. Here, we investigated the effect of Icariside II (ICA‐II) on RIF and explored the underlying mechanisms. Rats receiving 5/6 ablation and infarction (A/I) surgery were gavaged with ICA‐II (5 or 10 mg/kg) for 8 weeks. In vitro, TGF‐β1‐stimulated NRK‐52E cells were treated with ICA‐II and (or) oleic acid, etomoxir, ranolazine, fenofibrate, and GW6471. The effects of ICA‐II on RIF, fatty acid oxidation, lipid deposition, and mitochondrial function were determined by immunoblotting, Oil red O staining, colorimetric, and fluorometric assays. Using adeno‐associated virus injection and co‐culture methods, we further determined mechanisms of ICA‐II anti‐RIF. ICA‐II ameliorated the fibrotic responses in vivo and in vitro. RNA‐seq analysis indicated that ICA‐II regulated fatty acid degradation and PPAR pathway in 5/6 (A/I) kidneys. ICA‐II attenuated lipid accumulation and up‐regulated expression of PPARα, CPT‐1α, Acaa2, and Acadsb proteins in vivo and in vitro. Compared to ICA‐II treatment, ICA‐II combined with Etomoxir exacerbated mitochondrial dysfunction and fibrotic responses in TGF‐β‐treated NRK‐52E cells. Importantly, we determined that ICA‐II improved lipid metabolism, fatty acid oxidation, mitochondrial function, and RIF by restoring PPARα. Co‐culture revealed that ICA‐II decreased the expression of Fibronectin, Collagen‐I, α‐SMA, and PCNA proteins in NRK‐49F cells by restoring PPARα of renal tubular cells. ICA‐II may serve as a promising therapeutic agent for RIF in 5/6 (A/I) rats, which may be important for the prevention and treatment of CKD.

15 Sep 2023·European journal of pharmacology

Network pharmacology analysis of Icariside II against bladder cancer.

Article

Author: Li, Yawei ; Wang, Jinhua ; Zhou, Yihong ; Hu, Huating ; Tang, Yuxin ; He, Kancheng ; He, Yuanqiao ; Xie, Nengqing ; Huang, Zihao ; Chen, ZhaoYin

As a global health threat, bladder cancer (BC) is a common urological disease characterized by a high risk of progression and recurrence. Icariside II (ICA-II), a flavonol glycoside, exhibits antitumor ability in various tumors. However, there is no systematic study exploring the pharmacological mechanism of ICA-II in BC. We used public databases to obtain potential targets of ICA-II and related genes in BC. Bioinformatics analysis and molecular docking were used to identify potential targets and signaling pathways. Then, MTT, cell cycle assays and western blot (WB) were used to validate the predicted pathways in bladder cell lines, and in situ bladder cancer models were also established to verify the effect of ICA-II. Our research demonstrated that these ICA-II hub genes were related to the cell cycle. Then, our molecular docking analysis confirmed the interaction between ICA-II and CCNB1. In addition, our in vitro experiment demonstrated that ICA-II restrained the proliferation of BC cells mainly by blocking the cell cycle. WB also verified that ICA-II decreased the expression levels of CCNB1. In situ BC models showed that ICA-II had no hepatotoxicity or nephrotoxicity and could suppress the growth of in situ BC. In summary, during this study, we found that ICA-II had low toxicity in the kidney and liver. Network pharmacology was used, and both cell and animal experiments verified that ICA-II has a good therapeutic effect on bladder cancer, which may inhibit the proliferation and progression of bladder cancer by blocking the cell cycle of BC cells.

100 Deals associated with TBP-II

R&D Status

10 top R&D records.

to view more data

Indication	Highest Phase	Country/Location	Organization	Date
Malaria	Preclinical	IL	Yeda Pharma	-
Shock, Septic	Preclinical	IL	Yeda Pharma	-
Shock, Septic	Preclinical	CH	Merck Serono SA	-

Clinical Result

Indication

Phase

Evaluation

View All Results

Translational Medicine

Boost your research with our translational medicine data.

view full example data

Deal

Boost your decision using our deal data.

view full example data

Core Patent

Boost your research with our Core Patent data.

view full example data

Clinical Trial

Identify the latest clinical trials across global registries.

view full example data

Approval

Accelerate your research with the latest regulatory approval information.

view full example data

Regulation

Understand key drug designations in just a few clicks with Synapse.

view full example data

Chat with Hiro

Get started for free today!

Accelerate Strategic R&D decision making with Synapse, PatSnap’s AI-powered Connected Innovation Intelligence Platform Built for Life Sciences Professionals.

Start your data trial now!

Synapse data is also accessible to external entities via APIs or data packages. Empower better decisions with the latest in pharmaceutical intelligence.

Bio

Bio Sequences Search & Analysis

Chemical

Chemical Structures Search & Analysis


No Data

TBP-II

Overview

Basic Info

Related

R&D Status

Clinical Result

Translational Medicine

Deal

Core Patent

Clinical Trial

Approval

Regulation