Development of KLA-RGD integrated lipopeptide with the effect of penetrating membrane which target the αvβ3 receptor and the application of combined antitumor

Article

作者: Ma, Linhao ; Yan, Miaomiao ; Gu, XiuLian ; Wei, Guangcheng ; Niu, Mingcong ; Luo, Junlin ; Ji, Yiping ; Liu, Lu

Herein, an amphiphilic cationic anticancer lipopeptide P17 with α-helical structure was synthesized based on the integration of KLA and RGD peptide which could bind with the receptor of integrin α_vβ₃. P17 could self assemble into stable spherical aggregates in aqueous solution, and which could encapsulate the anticancer drugs (Such as Dox) to form P17 @ Anticancer drug nanomedicine (P17 @ Dox nanomedicine) which could play the combined therapy of P17 and anticancer drugs (Dox). The encapsulation efficiency of P17 aggregates to Dox was 80.4 ± 3.2 %, and the release behavior of P17 @ Dox nanomedicine in vitro had the characteristics of slow-release and pH responsiveness. The experiments in vitro showed that P17 lipopeptide had low cytotoxicity, high serum stability, low hemolysis and strong penetrating membrane ability. The release of Dox from P17 @ Dox in cells was time-dependment, and the P17 @ Dox nanomedicine had a good anticancer effect. The experiments in vivo showed that P17 and P17 @ Dox nanomedicine both had low hemolysis, and P17 @ Dox nanomedicine could effectively inhibit tumor growth and significantly reduce the toxic and side effects of Dox. Molecular docking experiments showed that P17 could effectively interact with the receptor of integrin α_vβ₃. In conclusion, P17 lipopeptide could be used as an excellent drug carrier and play the combined anticancer effect of P17 and anticancer drugs.

2021-06-01·Journal of Chromatography B3区 · 医学

UPLC-Q-Exactive-MS analysis for hepatotoxicity components of Evodiae Fructus based on spectrum-toxicity relationship

3区 · 医学

Article

作者: Pan, Yingni ; Lv, Shuang ; Wang, Dongmei ; Zhang, Wei ; Ren, Kun ; Morikawa, Toshio ; Liu, Xiaoqiu ; Ren, Shumeng

Evodiae Fructus (EF) is generally divided into three categories: small flower EF (SEF), medium flower EF (MEF) and big flower EF (BEF) in commodity circulation according to the size of the fruit. It is a well-known and frequently used herbal medicine for treating gastrointestinal disorder-related stomachache and headache, which has aroused wide attention for its hepatotoxicity. However, reports about hepatotoxicity is controversial and hepatotoxic components are inconclusive. The study aimed to explain the controversial hepatotoxicity of EF and screen the components associated with hepatotoxicity of EF based on the spectrum-toxicity relationship. UPLC fingerprints of 39 batches of EF collected from different regions were established. Combined with the results of L02 cell viability assays, the spectrum-toxicity relationship was investigated on the basic of orthogonal partial least squares (OPLS). The results of the research demonstrated that the toxicity of EF was obviously various among the different categories, in particularly, SEF was with less toxicity, MEF except for adulterants and BEF had mild toxicity and adulterants of MEF (A-MEF) produced more damage to L02 cell and no regions specificity in hepatotoxicity of EF. Thereinto, samples, the contents of which do not meet the requirements of Chinese Pharmacopoeia, were adulterants. It was worth noting that P11, P17, P20 and P25 were closely related to hepatotoxicity of EF and they were respectively identified as limonin (LIM), evodiamine (EVO), 1-methyl-2-nonyl-4(1H)-quinolone (MNQ), and 1-methyl-2-undecyl-4(1H)-quinolone (MUQ) by UPLC-Q-Exactive-MS. The hepatoprotection of P11 and hepatotoxicity of P17 were consistent with the results of spectrum-toxicity relationship. In summary, A-MEF was more toxic than other categories and SEF was less toxic than the others. It was noteworthy that EVO was the main hepatotoxic component of EF and LIM was the main hepatoprotective component of EF. The results provided worthy evidence for better utilization and development of EF.

2021-05-01·Cell Research

Structure-based development of three- and four-antibody cocktails against SARS-CoV-2 via multiple mechanisms

Letter

作者: Wang, Lei ; Wang, Yuxi ; Li, Weimin ; Zhu, Dandan ; Wang, Xiangxi ; Feng, Rui ; Zhang, Yanjun ; Sun, Yao ; Wang, Nan ; Yang, Peng ; Xing, Xiaorui

The ongoing COVID-19 pandemic caused by SARS-CoV-2 has resulted in an unprecedented public health crisis, galvanizing a global effort for rapidly developing new therapeutic strategies effective against COVID-19.To explore the possibility of the formulation of a cocktail containing three or four NAbs and test its effectiveness against SARS-CoV-2, we firstly examined the simultaneous binding of the three RBD-targeting NAbs to S trimer by competitive surface plasmon resonance.Full saturation of HB27 was revealed to occlude the attachment of P17 to the SARS-CoV-2 S trimer and vice versa.Interestingly, full occupancy of HB27 blocked the binding of H014 to the SARS-CoV-2 S trimer, whereas HB27 could still attach to the S trimer in the presence of excessive H014 which is line with structural observations of 0-3 bindings of H014 to the S trimer.By contrast, H014 and P17 were demonstrated to simultaneously bind to the SARS-CoV-2 S trimer.As expected, the binding of the NTD-targeting FC05 does not affect the interactions between any of the three RBD-specific NAbs and the SARS-CoV-2 S trimer.Not surprisingly, competitive binding assays verified a rational three-antibody cocktail consisting of FC05, H014 and P17 that simultaneously target three distinct regions.In most cases, binding of one NAb causes no notable changes in the binding affinities for other NAbs.These results highlight the potential of these antibodies in formulating three- and four-antibody cocktails where the antibodies work cooperatively.

项与 P-17 相关的新闻（医药）

2023-06-07

·PRNewswire

Sanyou's STAL helps researchers to explore the forefront of Life Sciences with high-impact literature publication

SHANGHAI, June 7, 2023 /PRNewswire/ -- Since the establishment of Super-Trillion Innovative Antibody Library (STAL), Sanyou has collaborated with or assisted scientists in publishing dozens of articles, of which 41 have a cumulative impact factor of 412.32, 14 papers have an impact factor greater than 10 and the highest impact factor is 47.728. ( Get complete literature information: ) We have made an inventory of some high-quality papers to demonstrate how the STAL help researchers to conduct in-depth studies and explore the forefront of life sciences. Representative Paper No.1 Title: Defining variant-resistant epitopes targeted by SARS-CoV-2 antibodies: A global consortium study Journal: Science IF: 47.728 PMID: 34554826 Publication Date: 2021.1 Conclusion and Significance: Based on different epitopes, the authors divided 186 monoclonal antibodies that bind the receptor-binding domain (RBD) of SARS-CoV-2 from global sources into 7 categories, and analyzed the binding conformation and blocking neutralization effects of monoclonal antibodies from different categories. Contribution or Participation: The Collaborative institutions include the Centrer for Infectious Diseases and Vaccine Research in La Jolla Institute for Immunology, the Duke Human Vaccine Institute at Duke University, etc. Sanyou Biopharma is the joint signature party. Sanyou obtained antibodies targeting the Spike protein of different mutant strains through the screening of its super trillion antibody libraries and selected antibody molecules with the best in vitro performance for structural analysis and was selected as a typical type of antibody. No.2 Title: Rational development of a human antibody cocktail that deploys multiple functions to confer Pan-SARS-CoVs protection Journal: Cell research IF: 25.617 PMID: 33262452 Publication Date: 2021.9 Conclusion and Significance: The authors obtained the antibody P17 with high blocking activity that specifically targets the RDB region and does not compete with the H014 antibody by screening the Sanyou Super-Trillion series Innovative Antibody Library. The preventive and therapeutic efficacy of the combined use of P17 and H014 was further verified by in vitro experiments. Additionally, in terms of structure, through Cryo-EM, the authors analyzed the tertiary complex structure of the SARS-CoV-2 S trimer, P17 and H014, elucidating the synergy caused by the different epitopes between the two effects. Contribution or Participation: The collaborative institutions include National Clinical Research Center for Infectious Diseases, Key Laboratory of Infection and Immunity at the Chinese Academy of Sciences, and the Institute of Microbiology and Epidemiology at the Academy of Military Medical Sciences, etc. Sanyou is the co-first author and co-corresponding author. The P17 antibody was screened through Sanyou's Super-Trillion series Innovative Antibody Library (Fully human naïve antibody library, ST-ST-HuNAL, Fab format). The neutralizing effect of its high affinity and high-blocking effect was determined through Sanyou's in vitro efficacy platform, which assisted the discovery and identification of COVID-19 antibodies. No.3 Title: An Engineered IgG–VHH Bispecific Antibody against SARS-CoV-2 and Its Variants Journal: Small Method IF: 14.188 PMID: 36300882 Publication Date: 2022.12 Conclusion and Significance: The authors initially screened a fully human antibody R15-F7, and a humanized nanobody P14-F8-35, as the raw materials of the bispecific antibody. In vitro functional experiments confirmed the strong affinity and blocking activity of the two, and verified the epitope differences between the two through epitope competition. Subsequently, the configuration of the bispecific antibody, SYZJ001, was determined by design, and the in vitro affinity and blocking activity were verified to be superior to those of the two monoclonal antibodies. The pharmacokinetic studies in mice also indicated a good half-life of the bispecific antibody. Affinity experiments on different mutant strains showed a broad-spectrum blocking effect of the bispecific antibody. Animal experiments further demonstrated the excellent therapeutic efficacy of the bispecific antibody. Contribution or Participation: The collaborative institutions include the Institute of Microbiology and Epidemiology at the Academy of Military Medical Sciences, etc. Sanyou is the co-first author and co-corresponding author. Both the humanized nanobody, P14-F8-35 and the fully human antibody R15-F7, are neutralizing antibodies screened from Sanyou's Super-Trillion series Innovative Antibody Library (Fully human naïve antibody library and alpaca trillion antibody library). Furthermore, the configuration design and functional validation of the bispecific antibody were also completed by Sanyou's platform, which provided sufficient raw materials for the structure analysis of the complex. You can get more information here: About SANYOU Sanyou Biopharmaceuticals Co., Ltd. is a world-leading high-tech biotechnology enterprise focusing on R&D and services of innovative biological drugs. Sanyou is committed to bridge drug R&D and all-life-cycle manufacture supply chain, and has built the 4C business patterns that integrate "differentiated CRO, integrated CDO, innovative CPO and characteristic CRS", to accomplish the mission "to make it easy to discover innovative biological drugs anywhere". Since its establishment 8 years ago, Sanyou has maintained rapid growth. As of June 2023, the company has a professional team of nearly 300 employees, and most of them have a Ph.D. or master degree. Sanyou's team possesses rich experience in innovative drug development and industrialization. Sanyou has established an integrated innovative biological drug R&D laboratory of twenty thousand square meters with advanced facilities in Shanghai Caohejing Hi-Tech Park. Sanyou has built three industry-leading innovative technology platforms featured by "super-trillion, integration, and intelligence" , and has built more than 50 sub-platforms with the core innovative technologies represented by super-trillion phage display platform, and supported by platforms of material preparation, antibody discovery, molecule optimization, in vitro and in vivo efficacy, production cell line construction, upstream and downstream process development, preclinical R&D, industrialization development, etc. Sanyou keeps launching new technologies, new products, new services, and new scenarios based on principles of innovation, outstanding and reliability. The company has established friendly business collaboration with more than 1000 pharmaceutical companies, drug R&D institutions and diagnostics companies worldwide. Excellence and innovation, pursuit of dreams, striving and evolving, for the benefit of patients. Sanyou looks forward to jointly building a long-term collaborative growth ecosystem and a healthy community with our clients and partners. SOURCE Sanyoubio

疫苗免疫疗法

100 项与 P-17 相关的药物交易

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