Phase Ib, Two-centre, Randomised, Observer-blind, Placebo- and Comparator Controlled Trial to Evaluate the Safety, Tolerability and Antipsoriatic Efficacy of Three Strengths of a Topical SPS4251 Formulation in a Psoriasis Plaque Test

The current most important topical treatments for psoriasis are vitamin D3 analogues and/or corticosteroids. The possibility of another effective treatment for psoriasis could be based on the immunosuppressive efficacy of selective blockers of a lymphocyte potassium channel.
The aim of the clinical trial is to evaluate the safety, tolerability and anti-psoriatic efficacy of topical SPS4251 formulations in comparison to placebo and to a marketed topical Vitamin-D analogue ointment in a psoriasis plaque test.

开始日期2013-03-01

申办/合作机构

Circassia Ltd.

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100 项与 SPS-4251 相关的临床结果

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100 项与 SPS-4251 相关的转化医学

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100 项与 SPS-4251 相关的专利（医药）

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项与 SPS-4251 相关的文献（医药）

2025-12-31·Drug Delivery

Reliable high-PAP-1-loaded polymeric micelles for cancer therapy: preparation, characterization, and evaluation of anti-tumor efficacy

Article

作者: Liao, Naikai ; Ye, Fang ; Huang, Longping ; Li, Qi

The mitochondrial potassium channel Kv1.3 is a critical therapeutic target, as its blockade induces cancer cell apoptosis, highlighting its therapeutic potential. PAP-1, a potent and selective membrane-permeant Kv1.3 inhibitor, faces solubility challenges affecting its bioavailability and antitumor efficacy. To circumvent these challenges, we developed a tumor-targeting drug delivery system by encapsulating PAP-1 within pH-responsive mPEG-PAE polymeric micelles. These self-assembled micelles exhibited high entrapment efficiency (91.35%) and drug loading level (8.30%). As pH decreased, the micelles exhibited a significant increase in particle size and zeta potential, accompanied by a surge in PAP-1 release. Molecular simulations revealed that PAE's tertiary amine protonation affected the self-assembly process, modifying hydrophobicity and resulting in larger, loosely packed particles. Furthermore, compared to free PAP-1 or PAP-1 combined with MDR inhibitors, PAP-1-loaded micelles significantly enhanced cytotoxicity and apoptosis induction in Jurkat and B16F10 cells, through mechanisms involving decreased mitochondrial membrane potential and elevated caspase-3 activity. In vivo, while free PAP-1 failed to reduce tumor size in a B16F10 melanoma mouse model, PAP-1-loaded micelles substantially suppressed tumors, reducing volume by up to 94.26%. Fluorescent-marked micelles effectively accumulated in mouse tumors, confirming their targeting efficiency. This strategy holds promise for significantly improving PAP-1's antitumor efficacy in tumor therapy.

2025-06-01·Brain Research Bulletin

Pharmacological inhibition of Kv1.3 channel reduces sevoflurane-induced cognitive impairment through NLRP3-dependent microglial modulation

Article

作者: Zhang, Yang ; Yu, Li ; Ling, Yunzhi ; Li, Bowen ; Han, Huiyue ; Gao, Ying ; Wang, Zhu

Sevoflurane anesthesia is frequently linked to cognitive dysfunction in elderly individuals, with neuroinflammation, particularly microglial activation, playing a critical role in this pathology. Although the potassium channel Kv1.3 has been shown to regulate microglial activation, its involvement in sevoflurane-induced cognitive dysfunction remains poorly understood. In this study, cognitive dysfunction was induced in 17-month-old C57BL/6J mice by exposing them to 3 % sevoflurane for 5 h. Kv1.3 expression and cellular distribution were analyzed using RT-qPCR, Western blot, and immunofluorescence. To investigate the mechanisms underlying this process, mice were pretreated with the selective Kv1.3 inhibitor 5-(4-phenoxybutoxy)psoralen (PAP-1) or the NLRP3 inflammasome inhibitor MCC950 prior to sevoflurane exposure. Behavioral tests, hematoxylin-eosin (H&E) staining, nissl staining, immunohistochemistry, immunofluorescence, Western blot and enzyme-linked immunosorbent assay (ELISA) were performed for further assessment. Sevoflurane exposure led to a significant increase in Kv1.3 expression, which was strongly correlated with cognitive impairments and neuronal damage. Pharmacological inhibition of Kv1.3 with PAP-1 alleviated learning and memory deficits, reduced neuronal damage, and inhibited microglial activation. PAP-1 treatment also promoted the transition of microglia from a pro-inflammatory M1 phenotype to an anti-inflammatory M2 phenotype and suppressed NLRP3 inflammasome activation. Furthermore, the NLRP3 inflammasome inhibitor MCC950 also reduced microglial activation and phenotypic shift following sevoflurane exposure. These results suggest that Kv1.3 channel play a critical role in sevoflurane-induced cognitive dysfunction in aged mice through NLRP3-dependent microglial modulation. Targeting Kv1.3 could provide a potential therapeutic strategy for alleviating postoperative cognitive dysfunction associated with sevoflurane anesthesia.

2025-05-01·Translational Research

Kv1.3 expression on CD4 (+) T cells promotes interleukin-17A-associated airway inflammation and airway remodeling in asthma

Article

作者: Sun, Bingqing ; Lin, Jiangtao

BACKGROUNDDifferent types of T helper cells play an important role in disease severity and treatment response in patients with asthma. The potassium channel Kv1.3 is a type of potentially therapeutic target in T-cell-mediated inflammatory diseases.OBJECTIVEThis study aimed to explore the potential of Kv1.3 as a therapeutic target for asthma and to assess the efficacy of the Kv1.3 inhibitor PAP-1 in the treatment of asthma.METHODSKv1.3 expression on CD4⁺T cells was determined using data from public databases. CD4⁺T cells were isolated from peripheral blood samples obtained from healthy individuals and patients with asthma. The mouse models of OVA-induced asthma and Kv1.3 knockout were established. The underlying mechanism was investigated using mouse splenic CD4⁺T cells and BEAS-2B cells. OVA-induced asthmatic mice were treated with the Kv1.3 selective blocker PAP-1.RESULTSBased on public data, we determined the distribution of Kv1.3 on CD4⁺T cells, its up-regulation in asthma, and its correlation with Th17/Treg balance. Upregulation of Kv1.3 in CD4⁺T cells was associated with enhanced activation of these cells and airway inflammation in patients and mice with asthma, accompanied by increased IL-17A levels in alveolar lavage fluid. Conversely, Kv1.3 deficiency significantly attenuated airway inflammation, lowered IL-17A levels in bronchoalveolar lavage fluid, and inhibited airway epithelial-mesenchymal transition in asthmatic mice. Furthermore, treatment with the Kv1.3 selective blocker PAP-1 attenuated inflammation in lung tissues and prevented airway remodeling in OVA-induced asthmatic mice.CONCLUSIONSKv1.3 expression on CD4⁺ T cells was correlated with IL-17A-associated airway inflammation and remodeling in asthma, which may be regarded as a potential diagnostic marker and therapeutic target for asthma.TRANSLATIONAL SIGNIFICANCEBased on our study, Kv1.3 expression on CD4⁺T cells was correlated with IL-17A-associated airway inflammation and remodeling in asthma, which may be regarded as a potential diagnostic marker and therapeutic target for asthma. The treatment with the Kv1.3 selective blocker PAP-1 attenuated inflammation in lung tissues and prevented airway remodeling in OVA-induced asthmatic mice. Our discoveries offer novel perspectives for a better understanding of IL-17A-associated airway remodeling in asthma. The development of drugs targeting Kv1.3 holds application value for IL-17A-associated asthma.

项与 SPS-4251 相关的新闻（医药）

2023-12-19

·佰傲谷BioValley

核心管线挫折引发的两次大裁员

拥有全球首款的同种异体T细胞疗法的Atara Biotherapeutics公司如今同样面临现金流的困境。近日（2023年12月18日），Atara将于今年年底裁员近100人，这是上个月公司的一款领先同种异体T细胞疗法Ⅱ期临床失败后，公司进行战略重组的一部分（30%）。截止2023第三季度，Atara净亏损6980万美元，现金流约1.02亿美元，公司预计裁员后其现金流（加上未来其他收入）将支撑公司运营到2025年第三季度。首款上市产品的低期待值Atara成立于2012年，总部位于加州旧金山，由安进与风投机构凯鹏华盈(KPCB)共同出资创建，主要致力于开发肿瘤、自身免疫性疾病和病毒性疾病的同种异体T细胞疗法。Atara的“off-the-shelf”T细胞疗法旨在利用健康人群的PBMCs(人外周血单个核细胞)，经基因改造变为具有精确靶向、适用各类人群的通用型的“off-the-shelf”细胞毒性T细胞。相比较于传统的CAR-T细胞疗法，其具有无需个体化制备、扩增快速等优点。2022年12月19日，Atara的首款T细胞疗法Ebvallo（tabelecleucel）获得了欧盟委员会（EC）批准上市，作为既往接受过至少一种治疗的复发性/难治性EB病毒（EBV）相关的移植后淋巴细胞组织增生性疾病（EBV+PTLD）患者（≥2岁）的单药疗法。这也是全球首款获得监管机构批准的同种异体T细胞疗法。2023年5月，Ebvallo在英国也获得了批准。不过，作为公司的首款上市产品，Ebvallo似乎并没有支撑外界对Atara太多期待。Ebvallo针对的适应症PTLD非常罕见，其发病率约为1%-30%，在美国仅有几百名患者。在一些分析师看来，仅凭目前的适应症，Ebvallo的销售峰值最多可能也就1.4亿美元。Atara自己也坦言，Ebvallo并不会很快成为公司的收入来源，事实上，自获批半年多以来，Ebvallo的销售表现并未掀起太大波澜。由于商业化经验方面不足等问题，Ebvallo在欧洲市场其他选定市场的商业化被Atara移交给了其合作伙伴Pierre Fabre。ATA188引发的两次裁员公司希望寄于在其另一款ATA1在研管线ATA188身上，这也是公司临床进展最快的管线。ATA188是一种同种异体(EBV) T细胞疗法，靶向EBV感染的B细胞和浆细胞，包括中枢神经系统内的细胞和浆细胞。在先前公司报告的临床I期试验中，接受ATA188治疗的进行性多发性硬化症（PMS）患者病情改善了33%。然而推进到II期临床后ATA188就开始变脸。2022年7月13日，一项名为EMBOLD的Ⅱ期临床试验中期分析结果表明，其六个月的数据不足以得出关于ATA188是否会在12个月内带来益处的结论。独立数据和安全监测委员会认为六个月的中期终点可能是对这种干预措施在这种情况下的潜力的不准确衡量。之后不久Atara就做出了裁员20%的决定，裁员总数77人。2023年11月8日，Atara公布了EMBOLD临床最终分析结果，ATA188组患者的残疾改善率为6%，而安慰剂组的改善率为16%，未达到扩展残疾状况量表 (EDSS) 确认残疾改善 (CDI)的临床主要终点目标，试验宣告失败。市场对此反应更为剧烈，Atara股价暴跌80%。Atara总裁兼首席执行官Pascal Touchon表示公司对结果感到惊讶和深感失望。一天后（11月10日），Atara就宣布进行了重组，并表示大幅削减对ATA188的研发支出，将集中资源到其他同种异体CAR-T管线开发上。伴随重组的是30%的裁员计划。参考出处：Atara：明年二季度在美提交首款“现货”T细胞疗法BLAhttps://www.fiercebiotech.com/biotech/atara-stock-plummets-3x-afterhours-following-mystifying-phase-2-data-reviewhttps://www.biospace.com/article/promised-cuts-begin-at-atara-as-77-jobs-on-the-block-/sponse本周好文推荐如需转载请联系佰傲谷并在醒目位置注明出处﹀ ········

细胞疗法财报免疫疗法临床2期临床1期

100 项与 SPS-4251 相关的药物交易

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研发状态

10 条进展最快的记录,

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适应症	最高研发状态	国家/地区	公司	日期
银屑病	临床1期	-	Airmid Healthgroup	-
斑块状银屑病	药物发现	德国	Circassia Ltd.	2013-03-01
寻常性银屑病	药物发现	德国	Circassia Ltd.	2013-03-01
特应性皮炎	药物发现	英国	Circassia Ltd.	-