Evaluation of Phoxilium® to Prevent HypoPHOSPHATEmia compared to Hemosol B0® or Prismocol B22 during Citrate-based Continuous Renal Replacement Therapy (CRRT) in the Intensive Care Unit (ICU)

开始日期2023-12-05

申办/合作机构

Austin Health

100 项与 B-022 相关的临床结果

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100 项与 B-022 相关的转化医学

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100 项与 B-022 相关的专利（医药）

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项与 B-022 相关的文献（医药）

2024-12-01·European Journal of Medicinal Chemistry

Identification of novel indolinone derivatives as CTSC inhibitors to treat inflammatory bowel disease by modulating inflammatory factors

Article

作者: Tao, Fangbiao ; Shi, Daxing ; Lou, Yan ; Liu, Xinhua ; Zhou, Feilong ; Chen, Xing

Novel inflammatory bowel disease (IBD) therapeutic drugs, mainly biologics that neutralize pro-inflammatory factors and janus kinase inhibitors that inhibit cytokine-mediated signal transduction, face problems including low efficacy rates, limited therapeutic benefits, and infection risks. It is an important task to find proteins that broadly regulate a variety of cytokines and to develop corresponding drugs. Cathepsin C (CTSC) mediates neutrophil-related inflammatory, participates in the recruitment and activation of inflammatory cells, and regulates cytokines levels, and is considered an ideal target for IBD treatment. In this study, starting from the in-house molecule, through medicinal chemistry and target-based design, a novel CTSC inhibitor B22 with IBD therapeutic efficacy was discovered. In vitro target verification and mechanism study indicated that B22 inhibit CTSC activity by binding to S2 pocket and S1 site, further inhibiting downstream serine protease activity. In addition, B22 exhibited anti-inflammatory activity and regulated various cytokines levels. In vivo studies highlighted B22 bears acceptable toxicity and suitable pharmacokinetic properties, and displays anti-inflammatory activity in IBD model. In conclusion, B22 is a potential anti-inflammatory molecule for IBD by targeting CTSC and deserves further research.

2024-11-01·Liver International

Lymphotoxin beta‐activated LTBR/NIK/RELB axis drives proliferation in cholangiocarcinoma

Article

作者: Sobol, Benjamin ; Korell, Felix ; Nader, Luisa ; Isele, Hanna ; Schmitt, Nathalie ; Köhler, Bruno C. ; Ramadori, Pierluigi ; Nichetti, Federico ; Gärtner, Ulrike ; Xu, Kaiyu ; Mock, Andreas ; Volk, Julia ; Jäger, Dirk ; Fröhling, Stefan ; Vaquero‐Siguero, Nuria ; Springfeld, Christoph ; Scherr, Anna‐Lena ; Jackstadt, Rene ; Albrecht, Thomas ; Kessler, Annika ; Roessler, Stephanie ; Dill, Michael T. ; Lenoir, Bénédicte ; Nieto, Osama Azzam ; García‐Beccaria, María ; Hoffmeister‐Wittmann, Paula ; Heikenwälder, Mathias ; Schwab, Maximilian ; Kelmendi, Eblina ; Hüllein, Jennifer ; Heide, Danijela ; Goeppert, Benjamin

AbstractBackground and AimsCholangiocarcinoma (CCA) is an aggressive malignancy arising from the intrahepatic (iCCA) or extrahepatic (eCCA) bile ducts with poor prognosis and limited treatment options. Prior evidence highlighted a significant contribution of the non‐canonical NF‐κB signalling pathway in initiation and aggressiveness of different tumour types. Lymphotoxin‐β (LTβ) stimulates the NF‐κB‐inducing kinase (NIK), resulting in the activation of the transcription factor RelB. However, the functional contribution of the non‐canonical NF‐κB signalling pathway via the LTβ/NIK/RelB axis in CCA carcinogenesis and progression has not been established.MethodsHuman CCA‐derived cell lines and organoids were examined to determine the expression of NF‐κB pathway components upon activation or inhibition. Proliferation and cell death were analysed using real‐time impedance measurement and flow cytometry. Immunoblot, qRT‐PCR, RNA sequencing and in situ hybridization were employed to analyse gene and protein expression. Four in vivo models of iCCA were used to probe the activation and regulation of the non‐canonical NF‐κB pathway.ResultsExposure to LTα1/β2 activates the LTβ/NIK/RelB axis and promotes proliferation in CCA. Inhibition of NIK with the small molecule inhibitor B022 efficiently suppresses RelB expression in patient‐derived CCA organoids and nuclear co‐translocation of RelB and p52 stimulated by LTα1/β2 in CCA cell lines. In murine CCA, RelB expression is significantly increased and LTβ is the predominant ligand of the non‐canonical NF‐κB signalling pathway.ConclusionsOur study confirms that the non‐canonical NF‐κB axis LTβ/NIK/RelB drives cholangiocarcinogenesis and represents a candidate therapeutic target.

2024-11-01·Brain Research

Inhibiting NF-κB inducing kinase improved the motor performance of ALS animal model

Article

作者: Guo, Moran ; Yi, Le ; Liu, Yakun ; Duan, Weisong ; Li, Chunyan ; Li, Zhongyao ; Cao, Mengjie ; Li, Yuanyuan ; Tian, Yunyun ; Bi, Yue ; Xu, Xiangyang ; Sun, Jiaquan ; Xu, Yuyan

BACKGROUNDAmyotrophic lateral sclerosis (ALS) is a typical neurodegenerative disorder typically characterized by inflammation activation. However, the relationship between non-canonical NF-κB (ncNF-κB) pathway activation and ALS progression is not clear.METHODSWe tested the ncNF-κB pathway in the ALS animal model including hSOD1-G93A transgenic mice and TBK1 deletion mice.We treated age-matched SOD1-G93A mice with B022 (a NIK inhibitor) to investigate the role of NIK in the ALS animal model. We also established a new mice model by crossing SOD1-G93A mice with NIK^+/- mice to further evaluate the interrelationship between the NIK and the disease progression in ALS animal model.RESULTSIn this study, we found the ncNF-κB pathway was activated in SOD1-G93A animal model and TBK1 deletion model. Inhibition of NIK activity by small molecule B022 significantly improved the motor performance of the ALS animal model. However, NIK deletion enhanced the mutant SOD1 toxicity by inflammatory infiltration.CONCLUSIONTBK1 deletion and mutant SOD1 shared the common pathological feature possibly via effects on NIK activation and inhibitor of NIK could be a novel strategy for treating ALS.

100 项与 B-022 相关的药物交易

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研发状态

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适应症	最高研发状态	国家/地区	公司	日期
炎症	临床前	中国	中国药科大学	2024-04-02
肝炎	临床前	中国	东北师范大学	2016-11-08
肝损伤	临床前	中国	东北师范大学	2016-11-08