Spleen tyrosine kinase (SYK) has emerged as a promising therapeutic target for cancer treatment. In this study, based on the lead compound Lanraplenib, a series of novel imidazo[1,2-a]pyrazine derivatives were designed and synthesized through structure-based optimization focusing on modifications at the solvent-exposed C-8 position. The synthesized compounds were evaluated for their in vitro SYK inhibitory activity, and most of them exhibited improved potency. Among them, compound B13 showed the highest activity with an IC₅₀ value of 10.9 nM, comparable to Lanraplenib. In vitro studies demonstrated that B13 displayed significant anti-proliferative effects against SKOV3, MDA-MB-231 and HepG2 cells, and effectively inhibited colony formation. Mechanistic studies revealed that B13 induced S phase cell cycle arrest and promoted apoptosis in a dose-dependent manner. Molecular docking suggested that the enhanced activity of B13 may be attributed to enhanced hydrophobic interactions and additional hydrogen bonding within the SYK binding pocket. Furthermore, B13 exhibited moderate metabolic stability in liver microsomes. In vivo studies using a SKOV3 xenograft model demonstrated that B13 significantly inhibited tumor growth in a dose-dependent manner, with tumor inhibition rates of 58.62% and 66.97% at 30 and 60 mg/kg, respectively, better than Lanraplenib, while showing no obvious toxicity. Collectively, these findings identify B13 as a promising SYK inhibitor and provide valuable insights for the further development of SYK targeted therapeutics for solid tumors.

2026-09-01·CYTOKINE

Efficacy and safety of IgG-pathway inhibitors in adult immune thrombocytopenia: A systematic review and meta-analysis with subgroup analyses of FcRn and SYK inhibitors

Review

作者: Alsalhen, Bashar Zahir ; Almosilhy, Nereen A ; Kandil, Ahmed Hamdy ; Chukr, Mawadda ; Almasalma, Mousa ; Maarouf, Mohamed Lotfy ; Soliman, Weaam A ; Mohamed, Ahmed S ; Altaamreh, Sara Mohammad ; Al-Qadi, Mahmoud Hashem ; Boshta, Ahmed

BACKGROUND:

Immune thrombocytopenia (ITP) is an autoimmune disorder characterized by platelet counts <100 × 10⁹/L and increased bleeding risk. Novel therapies, including spleen tyrosine kinase (SYK), neonatal Fc receptor (FcRn), and Bruton's tyrosine kinase (BTK) inhibitors, target the IgG pathway to improve platelet levels. Achieving ≥50 × 10⁹/L is associated with reduced bleeding risk.

OBJECTIVES:

To evaluate the efficacy and safety of SYK, FcRn, and BTK inhibitors in adult ITP.

METHODS:

A systematic review and meta-analysis was conducted according to PRISMA guidelines, including randomized controlled trials (RCTs) in adults with ITP. Primary outcomes were durable platelet response and overall response rate (ORR). Secondary outcomes included use of rescue therapy, adverse events (AEs), serious AEs, and discontinuation due to AEs.

RESULTS:

Ten RCTs from eight studies were included. SYK inhibitors showed the largest estimated effect (durable response RR = 10.26; overall response RR = 4.66). FcRn inhibitors provided moderate improvements in durable response but less consistent results for other outcomes. Only one RCT assessed BTK inhibitors, leaving their efficacy and safety uncertain. In an exploratory pooled analysis, IgG-pathway inhibitors were associated with significantly increased durable platelet responses (RR = 5.90) and ORR, and reduced rescue therapy use. Regarding safety, SYK inhibitors slightly increased any AEs but did not increase serious AEs or discontinuation rates, while FcRn inhibitors showed no significant safety concerns.

CONCLUSIONS:

SYK and FcRn inhibitors appear effective and generally safe, representing promising treatment options for ITP. However, more high-quality, longer-term RCTs with standardized platelet outcomes are needed, especially for BTK inhibitors, to better guide clinical decision-making.

2026-02-01·DRUG DEVELOPMENT RESEARCH

Recent Progress of Molecular Design and Activities of Spleen Tyrosine Kinase (SYK) Inhibitors

Review

作者: Yongdong Li ; Jiayi Shen ; Gonghui Li ; Sheng Chen ; Anzhi Li ; Yunyi Kong ; Jieman Lin

ABSTRACT:

Spleen tyrosine kinase (SYK), a non‐receptor tyrosine kinase, serves as a pivotal regulator in multiple intracellular signaling pathways, particularly those involved in immune responses. Dysregulated SYK activation has been strongly implicated in the pathogenesis of various hematological malignancies and autoimmune disorders, making it an attractive therapeutic target. Consequently, significant progress has been made in developing SYK inhibitors as a targeted treatment strategy. This article comprehensively reviews recent advances in SYK inhibitor research, focusing on their therapeutic potential in autoimmune diseases and hematologic cancers. Furthermore, we highlight representative SYK inhibitors, discuss their clinical applications, outline current challenges, and future directions in this evolving field.

项与 SYK inhibitors (Origenis) 相关的新闻（医药）

2023-12-28

·SYNAPSE

What are Syk inhibitors and how do you quickly get the latest development progress?

Syk (Spleen Tyrosine Kinase) is a crucial enzyme found in the human body that plays a significant role in immune cell signaling. It is primarily expressed in cells of the hematopoietic system, such as B cells, T cells, and mast cells. Syk acts as a key mediator in various immune responses, including B cell receptor signaling, Fc receptor signaling, and integrin signaling. By initiating downstream signaling cascades, Syk regulates immune cell activation, differentiation, and cytokine production. Due to its pivotal role in immune cell function, Syk has emerged as a potential therapeutic target for various immune-related disorders, including autoimmune diseases and certain cancers. The analysis of the current competitive landscape and future development of target Syk reveals that Rigel Pharmaceuticals, Inc., Novartis AG, HUTCHMED (China) Ltd., and TopiVert Ltd. are among the companies growing fastest under this target. These companies have made significant progress in the R&D of drugs targeting Syk, with drugs in the Approved and Phase 3 stages. Drugs targeting Syk have been approved for various indications, covering a wide range of diseases and conditions. Small molecule drugs are progressing most rapidly, indicating their potential as therapeutic options. The development of drugs targeting Syk is taking place in various countries/locations, with the United States, European Union, and China being prominent players. Further research and development are needed to fully explore the potential of drugs targeting Syk and address the inactive drugs in the pipeline. How do they work?Syk inhibitors are a type of medication that target and inhibit the activity of the spleen tyrosine kinase (Syk) enzyme. From a biomedical perspective, Syk is an enzyme involved in signaling pathways within immune cells, particularly B cells and mast cells. It plays a crucial role in the activation of these cells and the release of inflammatory mediators. Syk inhibitors work by binding to the Syk enzyme and blocking its activity. By inhibiting Syk, these medications can help regulate immune responses and reduce inflammation. They are primarily used in the treatment of certain autoimmune diseases, such as rheumatoid arthritis and immune thrombocytopenic purpura. These inhibitors are considered targeted therapies as they specifically target the Syk enzyme, minimizing potential side effects on other cellular processes. They can be administered orally or intravenously, depending on the specific medication. Syk inhibitors have shown promising results in clinical trials and are an active area of research in the field of biomedicine. List of Syk InhibitorsThe currently marketed Syk inhibitors include: Fostamatinib DisodiumMidostaurinSovleplenibIMG-016TOP-1630CerdulatinibEntospletinib DimesylateGusacitinibIC-265IC-270For more information, please click on the image below. What are Syk inhibitors used for?Syk inhibitors are primarily used in the treatment of certain autoimmune diseases, such as rheumatoid arthritis and immune thrombocytopenic purpura. For more information, please click on the image below to log in and search. How to obtain the latest development progress of Syk inhibitors?In the Synapse database, you can keep abreast of the latest research and development advances of Syk inhibitors anywhere and anytime, daily or weekly, through the "Set Alert" function. Click on the image below to embark on a brand new journey of drug discovery!

100 项与 SYK inhibitors (Origenis) 相关的药物交易

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