Chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) is a relatively inert B lymphocyte proliferative disease. In recent years with the launch of new drugs, chemotherapy has been gradually replaced by targeted therapy, which significantly prolongs the survival of patients and reduces the side effects of treatment. At present, BTK inhibitors, PI3K inhibitors, spleen tyrosine kinase (SYK) inhibitors and BCL-2 inhibitors are the most studied targeted therapeutic drugs for CLL/SLL. This article reviews the research progress of different types of targeted therapeutic drugs in the treatment of CLL/SLL.
UNASSIGNED: 慢性淋巴细胞白血病/小淋巴细胞淋巴瘤靶向治疗的最新研究进展.
UNASSIGNED: .慢性淋巴细胞白血病（CLL）/小淋巴细胞淋巴瘤（SLL）是一种相对惰性的B淋巴细胞增殖性疾病。近年来，随着新药的上市，化疗逐渐被靶向治疗所取代，明显延长了患者生存期并减低了治疗副作用。目前研究较多的CLL/SLL靶向治疗药物有BTK抑制剂、PI3K抑制剂、SYK抑制剂和BCL-2抑制剂。本文就不同种类靶向治疗药物在CLL/SLL治疗中的最新研究进展作一综述。.

OBJECTIVE: Hidradenitis suppurativa (HS) is a challenging skin disease with an underlying inflammatory process. Substantial progress has been made in our understanding of HS over the last few years, with the advancement of novel treatment approaches. The current systematic review aims to evaluate the safety and efficacy of Janus kinase (JAK) inhibitors and spleen tyrosine kinase (Syk) inhibitors in treating HS.
METHODS: A thorough systematic search was performed on PubMed/Medline, Web of Science, and Ovid Embase databases up to September 23th, 2023. Clinical studies published in English were included.
RESULTS: Our search yielded ten articles with a total of 165 patients treated with four types of JAK inhibitors (upadacitinib, povorcitinib, tofacitinib, and baricitinib) and one Syk inhibitor (fostamatinib). Upadacitinib, povorcitinib, and tofacitinib improved clinical outcomes, with a significant reduction in hidradenitis suppurativa clinical response (HiSCR) and abscess and inflammatory nodule count (AN count) during the treatment period. Also, these drugs are well tolerated in most HS patients with minimal adverse events (AEs). Moreover, baricitinib depicted an amelioration in signs and symptoms of HS in one case report. Also, fostamatinib exhibited favorable tolerability throughout a 12-week in moderate-to-severe HS patients. The remarkable clinical improvement, as assessed through HiSCR and hidradenitis suppurativa severity (IHS4), corresponded closely with serological indicators of inflammation following fostamatinib administration was achieved.
CONCLUSIONS: JAK and Syk inhibitors are potentially efficacious in managing moderate-to-severe HS since the proinflammatory cytokines are mediated by JAK and Syk signaling pathways. However, further research with a more rigorous examination is mandatory to evaluate such medication\'s long-term safety and efficacy.

Spleen tyrosine kinase (SYK) is a non-receptor tyrosine kinase. The dysregulation of SYK is closely related to the occurrence and development of allergic diseases, autoimmune diseases and cancer. SYK has become an attractive target for drug discovery due to its important biological functions. This article reviews the biological function of SYK, the relationship between SYK and disease, and therapies targeting SYK. In addition, inspired by new technologies such as proteolysis targeting chimeras (PROTACs) and phosphatase recruiting chimeras (PHORCs), we propose the development of new therapeutic approaches for targeting SYK, such as SYK PROTACs and SYK PHORCs, which may overcome deficiencies of existing methods.

Fostamatinib (Tavalisse®; Tavlesse®) is the first spleen tyrosine kinase (Syk) inhibitor approved for the treatment of chronic immune thrombocytopenia (ITP) in adult patients who have had an insufficient response to previous treatment. By inhibiting Syk activation in macrophages, fostamatinib blocks autoantibody-mediated platelet phagocytosis. In the placebo-controlled phase III FIT1 and FIT2 trials, 24 weeks of oral fostamatinib therapy increased platelet count in previously treated adults with ITP. A significantly higher proportion of patients achieved stable response with fostamatinib than with placebo in FIT1, but not in FIT2; however, pooled analyses of the two studies showed that fostamatinib produced significantly higher stable and overall response rates than placebo. Interim findings from the ongoing FIT3 open-label extension study suggested that the efficacy of fostamatinib was maintained with long-term treatment (up to 62 months; median duration 6 months), including in patients receiving fostamatinib as second- or later-line treatment. Fostamatinib had a generally manageable tolerability profile in all three FIT studies, with no serious safety risks. Fostamatinib therefore provides an alternative treatment option for chronic ITP in adult patients with an insufficient response to previous treatment.

BACKGROUND: The non-receptor tyrosine kinase, spleen tyrosine kinase (Syk), is primarily expressed in haematopoietic cells and appears to be particularly important in B cells. Syk is involved in signal transduction processes and appears to regulate allergic, inflammatory and autoimmune responses. It also appears to play a significant role in the development of haematological malignancies. Inhibitors of Syk are potentially useful in treating asthma, rheumatoid arthritis, lupus, chronic lymphocytic leukaemia and lymphomas.
METHODS: This article reviews the increasing number of patent filings between 2010 and 2013 claiming Syk inhibitors and focuses on the multiple structural classes of Syk inhibitors disclosed. It also comments on recent developments with Syk inhibitors, both clinical results and licensing deals.
CONCLUSIONS: The increased interest in the identification of Syk inhibitors has seen a sharp increase in patent filings claiming such compounds. However, the number of these is well below that of filings relating to other pro-inflammatory kinases (p38, JAK). These filings have also claimed an increasingly diverse range of chemical classes moving away from the 2,4-diaminopyrimidine motif present in drugs such as fostamatinib and PRT-06207. Many of the claimed compounds are Syk inhibitors with potencies considerably better than fostamatinib. However, good kinase selectivity is also likely to be essential if a Syk inhibitor is to prove useful enough to emulate the JAK inhibitor tofacitinib in gaining marketing authorisation. Recent clinical failures with Syk inhibitors are expected to result in a decrease in the rate of patent filings claiming Syk inhibitors.

Spleen tyrosine kinase (Syk), a member of Syk family of non-receptor protein tyrosine kinases plays a significant role in the immune cell signaling in B cells, mast cells, macrophages and neutrophils. Anomalous regulation of this kinase can lead to different allergic disorders and antibody-mediated autoimmune diseases such as rheumatoid arthritis, asthma, psoriasis and allergic rhinitis. Being involved in the growth and survive mechanism of B cells, its inhibition can be beneficial in B-cell lymphoma. Thus, Syk can be sited as a therapeutically relevant target for various allergic and autoimmune disorders. This review article describes the structure of Syk and its role in B-cell signaling. In addition to this, data regarding small molecule inhibitors of Syk has also been reviewed from different papers and patents published.

Platelet is activated through signal transduction, that mainly includes phospholipase-beta (PLCbeta) pathway, protein tyrosine kinases (PTK) pathway, phosphatidylinositol3-kinase (PI3-K) pathway, mitogen-activated protein kinases (MAPK) pathway, cyclic adenosine monophosphate-protein kinase A (cAMP-PKA) pathway and phospholipase A2 (PLA2) pathway. This article focuses on the relationship between signal transduction and platelet activation.