This phase II trial tests how well ziftomenib works in treating patients with NPM1 mutated or KMT2A rearranged acute myeloid leukemia (AML) and are not eligible to receive standard therapy. AML is often due to genetic changes in the cancer cells, including mutations in the NPM1 gene and rearrangements involving the KMT2A gene. These mutations result in activation of the menin pathway. Menin is a type of protein in the body that helps to regulate some of the naturally occurring processes in the body, but can also be involved in some types of cancers. Ziftomenib blocks this menin pathway and may prevent the cancer cells from continuing to grow. Giving ziftomenib may kill more cancer cells in patients with NPM1 mutated or KMT2A rearranged AML that are not eligible to receive standard therapy.

开始日期2026-01-10

申办/合作机构

Ohio State University Comprehensive Cancer Center

[+1]

NCT07214064

/ Not yet recruiting临床2期IIT

Safety and Feasibility of a Venetoclax- Augmented Treosulfan-Based Reduced Intensity Conditioning Before Allogeneic Stem Cell Transplantation in AML, MDS/AML and Higher Risk MDS

开始日期2026-01-01

申办/合作机构-

NCT07170592

/ Not yet recruiting临床1期

A Phase 1 Study of OTS-412 (Recombinant Oncolytic Vaccinia Virus) in Combination With Hydroxyurea or Hydroxyurea/Atezolizumab in Treatment-refractory Solid Tumor Patients

This clinical trial aims to determine whether the administration of the investigational drug OTS-412, OTS-412 in combination with hydroxyurea or hydroxyurea/atezolizumab is safe and effective for patients with various types of cancer.

开始日期2025-12-01

申办/合作机构

Bionoxx, Inc.

100 项与羟基脲相关的临床结果

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100 项与羟基脲相关的转化医学

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100 项与羟基脲相关的专利（医药）

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13,380

项与羟基脲相关的文献（医药）

2025-12-01·Toxicology reports

The Caenorhabditis elegans worm Development and Activity Test (wDAT) can be used to differentiate between reversible and irreversible developmental effects

Article

作者: Olejnik, Nicholas ; Yourick, Jeffrey ; Hunt, Piper Reid ; Sprando, Robert L

Developmental delay and spontaneous locomotor activity changes, as well as the reversibility of these adverse effects are apical endpoints used in chemical safety evaluations. These endpoints were assessed at sublethal concentrations in C. elegans using 5-fluorouracil (5FU), hydroxyurea (HU), or ribavirin (RV), teratogens that are associated with reduced fetal growth in mammals. C. elegans develop from egg to egg-laying adult in about three days. Synchronized cohorts were exposed either continuously, or for 24 h (early-only) from first-feeding after hatching. Developmental delays were dose-responsive for all three chemicals in both exposure schemes. For 5FU and HU, developmental delays and hypoactivity levels were similar in continuous and early-only exposure groups, consistent with irreversible developmental effects. The observed hypoactivity in developing C. elegans may be related to reported 5FU-induced muscle impairment and HU-induced post-exposure effects on locomotion parameters in mammals. In contrast to 5FU- and HU-induced hypoactivity, RV was associated with a non-significant trend to slight hyperactivity in both exposure schemes. Continuous RV exposures induced delays to sequential developmental milestones that increased with exposure duration. RV-induced delays were significantly reduced but not eliminated in early-only exposure cohorts, consistent with cumulative RV effects on developmental progress. These findings suggest that C. elegans may be a useful model for detecting chemicals with irreversible, reversible, and/or cumulative effects on organismal development.

2025-12-01·Current Hematologic Malignancy Reports

Contemporary CMML Risk Stratification and Management

Review

作者: Syal, Arjun ; Tremblay, Douglas ; Sastow, Dahniel

PURPOSE OF REVIEW:

Chronic myelomonocytic leukemia (CMML), a rare myelodysplastic/myeloproliferative neoplasm (MDS/MPN) overlap syndrome, poses diagnostic and therapeutic challenges due to its heterogeneity and rarity. This review highlights updates to CMML diagnostic criteria, examines risk stratification models and their clinical implications, and outlines both established and emerging therapies for this rare and likely underrecognized hematologic malignancy.

RECENT FINDINGS:

Updated diagnostic criteria from 2022 reduce the monocyte threshold to 0.5 × 10⁹/L for CMML diagnosis, which will reclassify many cases previously diagnosed as MDS. Risk stratification models continue to be refined allowing for improved prediction and may help select appropriate patients for allogeneic stem cell transplantation, the only curative therapeutic modality in CMML. Although trials in CMML were long relegated to subpopulation of MDS studies, there has recently been a flourishing of novel therapies being tested specifically in CMML. These include lenzilumab (anti-GM-CSF) and IO-202 (anti-LILRB4), which have demonstrated promising early efficacy signals but require further study. Established treatments, which include hypomethylating agents and hydroxyurea as well as the JAK1/2 inhibitor ruxolitinib, provide limited survival benefits in CMML, underscoring the urgent need for novel therapeutic development. Coordinated dedicated research efforts have started to evaluate new agents in CMML. Along with further diagnostic and prognostic refinement, these advances are welcomed for this rare and heterogenous disease.

2025-12-01·MICRON

Optimized protocol for intracellular labeling of red blood cells with anti-hemoglobin F for confocal microscopy analysis

Article

作者: Isola, Ignacio ; Rey-Barroso, Laura ; Vilaseca, Meritxell ; Roldán, Mònica ; Burgos-Fernández, Francisco J ; Sarrate, Edurne ; Llobet, Anna Ruiz ; Frías, Marcos

The combined use of immunolabeling and confocal microscopy offers a robust tool for the comprehensive examination of red blood cells, allowing clear visualization of specific proteins and their roles in the cell. While immunolabeling is a widely employed technique, it presents specific challenges in the study of red blood cells, including difficulties with membrane permeabilization, the appearance of background fluorescence, detection of very faint signals, interference from other blood components, and, notably, poor preservation resulting from an incorrect choice of fixation components. Adding to this, fresh blood samples are very labile and need to be preserved as soon as possible, ideally immediately after extraction. Addressing these challenges requires careful experimental design to ensure assay specificity and sensitivity, often complicated by incomplete or unclear information in the literature. In this study, we have compiled available bibliographic data regarding key aspects of red blood cell immunolabeling and devised a detailed immunostaining protocol to investigate the presence of Hemoglobin F in patients with sickle cell anemia treated with hydroxyurea. This protocol ensures proper preservation of red blood cell characteristics and may find application in immunolabeling with other intracellular antibodies.

266

项与羟基脲相关的新闻（医药）

2025-10-03

·药明康德

致敬时代 | 五年生存率跃升6倍，多款新型抗癌药为这类患者点亮希望

编者按：2025年，药明康德迎来创立25周年的重要里程碑。值此契机，我们向所有与我们共同书写产业变革篇章的科学家、医药人和投资者致以衷心感谢与诚挚敬意，也特别推出“致敬时代”系列，回顾全球同仁如何借助科学与合作的力量，不断拓展治疗边界、改善患者命运。四分之一个世纪的坚守，只为加速每一款新药的诞生。下一个25年，我们将继续心怀感恩与敬畏，依托独特的CRDMO模式，与全球伙伴携手同行，共赴健康未来。急性髓系白血病（AML）是成年人中最常见的白血病类型之一，多发于60岁及以上的人群，但也可能累及年轻人和儿童。据流行病学统计，2021年全球新发AML病例数超14万例。AML病情发展迅猛，如果不及时接受治疗，患者可能在几周到几个月内就发展为重症并死亡。面对这一高危疾病，AML的治疗策略近年来取得显著进展。除传统化疗、放疗及造血干细胞移植外，靶向药物、免疫疗法、细胞治疗及抗体偶联药物（ADC）等新型治疗方式逐步应用于临床，推动疗效不断提升。数据显示，过去几十年间，AML患者的5年生存率已从1975年的5.4%提升至2017年的33.7%，增长近6倍。在推动AML治疗革新的进程中，药明康德依托25年的行业深耕，不仅见证了AML治疗药物从实验室走向临床转化应用的突破历程，同时凭借其独特的CRDMO业务模式，助力全球合作伙伴加速包括AML在内的多种疾病创新疗法的研发进程，为全球患者带来更多治愈希望。从“脓血”疑云到解密白血病细胞的200年之路 AML的认知经历了两个世纪的探索。19世纪初，医学文献中已零星记载了一类血液异常病例：患者常伴发热、虚弱、肝脾肿大，血液外观呈乳糜状或脓血样。当时虽未精准归类，但这些现象已提示存在一种独特血液疾病。 1845年，显微镜技术带来了关键突破。英国医生约翰·休斯·贝内特（John Hughes Bennett）报道了首例白血病病例：一名28岁男性患者脾肝显著肿大，血管内充斥乳白色脓液样物质。显微镜下，他观察到患者血液中布满无色球体（白细胞），与凝固的纤维蛋白丝交织，并由此提出“白血球增多症（leucocythemia）”的概念，首次明确该病为原发性全身性血液疾病，而非感染引发的继发表现。 ▲贝内特所绘制的白血病患者血液中的无色球体（图片来源：参考资料[7]）贝内特的研究迅速引发学界关注。同年，德国病理学家鲁道夫·菲尔绍（Rudolf Virchow）也报道了类似病例。他通过系统分析发现，患者体内白细胞异常增殖会抑制红细胞生成，进而指出：白细胞增多是疾病的本质特征，而非脓液形成所致。1847年，菲尔绍正式将这类疾病命名为“白血病（leukämie）”，并尝试将其分为脾源性和淋巴性两大类——虽然这一分类尚不精确，却为现代白血病分型奠定了基础。 19世纪下半叶，随着病例积累，白血病逐渐被确认为独立疾病实体，临床与病理学研究的深入，也为探索其本质创造了条件。 1870年代，德国医学家保罗·埃利希（Paul Ehrlich）改进了血细胞染色技术，使血细胞结构清晰可见，进而首次识别出“原始细胞”——即未成熟的血细胞前体（现代医学中的造血干细胞）。埃利希还提出根据病程快慢和细胞成熟度，将白血病分为急性、慢性两大类：急性白血病以未成熟原始细胞大量增殖、病情进展迅速为特征；慢性白血病则由相对成熟但功能异常的细胞增殖主导，进展缓慢。这一分类框架逐步演化为现代白血病四大亚型：AML、急性淋巴细胞白血病（ALL）、慢性髓系白血病（CML）和慢性淋巴细胞白血病（CLL）。从19世纪对“脓血”现象的误解，到埃利希时代对白血病细胞分化特征的精准界定，人类对AML的认识已从宏观深入微观。这些历史积累不仅奠定了现代血液学的基础，更为后续AML分子机制研究与靶向治疗的开发提供了不可或缺的科学前提。化疗筑基，靶向疗法为特殊患者群体破局数十年来，AML的治疗策略经历了从传统化疗到精准靶向治疗的演进。以阿糖胞苷联合蒽环类药物（如柔红霉素或去甲氧柔红霉素、伊达比星）的“7+3方案”为代表的强化诱导化疗，曾长期作为年轻、体健且携带良好风险特征AML患者的基础治疗方案，使部分患者获得长期缓解。然而，AML多发于老年人群，多数患者年龄超过65岁，常因合并症、高危遗传学异常及对强化化疗耐受差等因素，临床预后不佳。针对不适合强化化疗的患者，去甲基化药物如阿扎胞苷的应用显著改善了患者的生存结局。时至今日，传统化疗药物仍构成AML治疗的重要支撑，除“7+3”方案常用药物外，还包括克拉屈滨、氟达拉滨、米托蒽醌、依托泊苷、羟基脲、皮质类固醇（如泼尼松或地塞米松）、甲氨蝶呤、6-巯基嘌呤（6-MP）、地西他滨。随着脂质体递送系统的进步，复方制剂如Vyxeos（柔红霉素/阿糖胞苷脂质体）也进一步优化了传统AML治疗药物的治疗指数。图片来源：123RF 近年来，针对癌细胞特定分子组分的靶向药物迅速发展，显著改变了AML的治疗格局。靶向药物通过特异性抑制白血病细胞的异常信号通路或分子标志，不仅为复发/难治性AML提供了新选择，也逐渐进入一线治疗，为老年及不耐受化疗的脆弱患者群体带来了希望。从4000个化合物中筛出的希望，开启AML靶向治疗新篇在众多分子靶点中，FLT3基因突变尤为关键。FLT3是一种受体酪氨酸激酶，调控造血干细胞的增殖、分化与存活。其突变可促进白血病细胞无限增殖并抑制凋亡，特别是FLT3-ITD突变，与AML预后不良密切相关。随着机制研究的深入，FLT3被确立为AML治疗的重要靶点。 FLT3抑制剂的研发起步于约翰斯·霍普金斯大学唐纳德·斯莫尔（Donald Small）博士团队。上世纪90年代，斯莫尔博士克隆出了首个人类FLT3基因并揭示了其在AML中的致病作用。由于当时缺乏高通量筛选工具，研究团队利用96孔板手动筛选了4000余种化合物，最终发现CEP-701（lestaurtinib）为潜在FLT3抑制剂。随后，通过实验室和动物模型验证，并构建FLT3活性检测方法，研究人员进一步明确了其作用机制。临床研究显示，CEP-701可清除AML患者外周血中的白血病细胞，在部分患者体内甚至还能清除白血病细胞的发源地——骨髓中的白血病细胞。但这种疗效是暂时的，且存在药物与血浆蛋白结合过强等缺陷，最终限制了其应用。基于斯莫尔博士团队的发现以及其他研究成果，新一代的FLT3抑制剂逐步克服了这些局限性。数年后，研究者意外发现多激酶抑制剂Rydapt（midostaurin，米哚妥林）竟是一种强效FLT3抑制剂。该药物最初作为PKC抑制剂开发，在实体瘤模型中展现出抗增殖活性。体外实验表明，米哚妥林可在极低浓度下抑制FLT3-ITD阳性小鼠原B细胞株增殖，并通过诱导凋亡和阻滞细胞周期发挥作用。在动物模型中，其口服治疗显著改善了移植FLT3-ITD骨髓小鼠（模拟AML模型）的生存。由于该药物的安全剂量已在其他疾病患者中确立，研究人员迅速将其应用于AML临床试验。在早期单药研究中，米哚妥林虽能降低外周血原始细胞计数，但完全缓解率有限，引发了对其疗效的质疑。然而，联合治疗方案改变了这一局面：米哚妥林与标准化疗联合使用，显著提高了AML患者的治疗结局。最终，2017年，美国FDA批准米哚妥林联合标准阿糖胞苷+柔红霉素诱导治疗及阿糖胞苷巩固治疗，用于FLT3突变阳性的成人AML患者。图片来源：123RF 米哚妥林的成功标志着AML靶向治疗的开端，也推动了更多高效、选择性更强的FLT3抑制剂相继问世。其中，Xospata（gilteritinib，吉瑞替尼）于2018年获FDA批准，用于复发/难治性FLT3突变AML；2023年，Vanflyta（quizartinib）也获得FDA批准，可联合化疗用于新确诊FLT3-ITD阳性AML成人患者，并在巩固化疗后可作为维持治疗单药使用。不杀死癌细胞也能治病的抗癌药在AML研究的另一条路径上，科学家的目光逐渐转向了癌细胞代谢。2009年，基因测序揭示了一个意外的发现：异柠檬酸脱氢酶（IDH）基因在部分AML患者中发生突变。最初，这一结果让研究者颇感困惑，毕竟，IDH是糖代谢和三羧酸循环中的关键酶，长期以来并未被视为典型的癌基因。然而，深入研究揭示了谜底。IDH突变改变了细胞代谢的走向：原本应生成α-酮戊二酸（a-KG）的反应被打断，反而触发了其“逆向反应”，产生异常代谢物2-羟基戊二酸（2-HG）。2-HG的大量积累抑制了a-KG依赖性酶的活性，导致DNA甲基化紊乱和基因表达失调，由此使癌基因被激活、抑癌基因沉默。更为重要的是，这一代谢异常阻碍了造血细胞的正常分化，迫使其停留在“幼稚”的状态，从而推动白血病的发生与进展。研究者同时发现，在星形细胞瘤、胶质母细胞瘤等多种肿瘤中也存在IDH1/2突变，凸显了其在肿瘤发生中的普遍性作用，高水平的2-HG更是与AML的不良预后相关。由此，一个全新的治疗设想浮现：如果能够抑制突变IDH的功能，让分化阻滞解除，使白血病细胞重新分化为成熟血细胞，疾病或许就能被逆转。这一理念不同于“直接杀死癌细胞”的传统模式，而是采用了“诱导分化”的全新思路。带着这一希望，医药界纷纷针对IDH靶点开展研发工作。经过多年探索，IDH2抑制剂Idhifa（enasidenib）率先问世，并于2017年获得FDA批准，用于治疗IDH2突变的复发/难治性AML。随后，IDH1抑制剂Tibsovo（ivosidenib，艾伏尼布）在2018年被FDA批准用于IDH1突变的复发/难治性AML；2019年，其适应症扩展至一线治疗——适用于≥75岁或因合并症无法耐受强化化疗的AML患者。2022年，FDA进一步批准艾伏尼布联合阿扎胞苷用于高龄（≥75岁）或其他不适合强化治疗的新确诊AML患者，显著拓宽了受益人群。同年，Rezlidhia（olutasidenib）也获FDA批准用于治疗IDH1突变的复发/难治性AML，为患者提供了更多选择。与依赖强烈细胞毒性的传统化疗不同，IDH抑制剂的作用机理别具一格：它们并不是直接摧毁癌细胞，而是通过解除分化阻滞，让“迷途”的白血病细胞回归正常发育轨迹，重新成为成熟的血细胞。这种“以分化代替杀伤”的新理念，为更多AML患者带来了与癌症长期共存甚至逆转疾病的希望。多靶点突破，AML治疗百花齐放随着靶向治疗的不断进展，AML治疗领域中多个关键靶点逐渐被开发，CD33、BCL-2、Hedgehog信号通路以及menin等靶点相继迎来突破性药物，持续推动AML治疗模式的革新。在CD33靶向药物方面，目前已获批的药物包括Mylotarg（gemtuzumab ozogamicin），其于2017年获美国FDA批准，用于新确诊的CD33阳性AML成人患者，以及2岁及以上的复发/难治性CD33阳性AML儿童和成人患者。 BCL-2抑制剂中，已有Venclexta（venetoclax，维奈克拉）获批上市。该药物于2018年获美国FDA加速批准，与阿扎胞苷/地西他滨或低剂量阿糖胞苷联合，用于≥75岁或因合并症无法接受强化化疗的AML患者一线治疗。在Hedgehog信号通路抑制剂方面，Daurismo（glasdegib）于2018年获FDA批准，可联合低剂量阿糖胞苷用于≥75岁或因合并症不适合强化化疗的新确诊AML成人患者，进一步拓宽了化疗不耐受人群的治疗选择。图片来源：123RF Menin抑制剂及DNA去甲基化药物组合也取得重要进展：2024年11月，美国FDA批准menin抑制剂Revuforj（revumenib）上市，用于治疗成人及≥1岁儿童中携带KMT2A易位的复发/难治性急性白血病患者；2023年，欧盟委员会批准Inaqovi（地西他滨 + cedazuridine），用于新确诊且不适合标准诱导化疗的AML成人患者，目前美国FDA已受理该药物与维奈克拉联合治疗同类患者的申请，预计将于2026年2月做出决定。在生物制品领域，已有多款药物用于AML辅助治疗：重组人粒细胞集落刺激因子Neutrogin（lenograstim）、Neupogen（filgrastim）在日本获批，用于缩短AML患者化疗后中性粒细胞恢复时间及发热持续时间；氨肽酶N（APN）抑制剂Bestatin（ubenimex，乌苯美司）上世纪80年代在日本获批用于AML维持治疗；硫鸟嘌呤（tabloid/tioguanine）早在上世纪60年代就获美国FDA批准，用于AML缓解诱导及巩固治疗；Ceplene（histamine dihydrochloride）在2008年获EMA批准，与IL-2联合用于首次缓解期AML成人患者的维持治疗。一体化CRDMO为AML患者带来曙光过去25年间，靶向疗法、免疫疗法和细胞疗法等创新治疗模式的不断涌现，持续重塑着血液癌症的治疗格局，让越来越多患者在延长生命的同时获得更好的生活质量。而这些疗法突破的背后，离不开科研人员对医学前沿的执着探索，以及产业伙伴间高效协同的支撑。长期以来，药明康德始终凭借“一体化、端到端”的CRDMO平台，持续赋能合作伙伴在血液癌症新药研发中不断突破，加速创新成果落地，惠及全球患者。在AML治疗领域，过去25年间，全球监管机构已先后批准了数十款AML创新疗法，为长期面临治疗困境的AML患者带来了新的治疗希望。作为创新的赋能者，药明康德很高兴能为其中多款疗法提供赋能，助力合作伙伴将这些创新疗法带到全球患者身边。在25年发展历程中，药明康德始终致力于支持全球合作伙伴从药物研究发现（R）、开发（D）到商业化生产（M）各个阶段的需求，助力突破性疗法加速研发进程。以血液肿瘤的小分子药物为例，药明康德化学服务平台能支持各种化学药物的分子形式及类别，满足从药物发现到商业化生产各个阶段、各个规模的各种物料需求。药明康德生物学业务平台作为综合性的早期发现和转化生物学赋能平台，能为包括血液肿瘤在内的多个疾病领域的新药研发提供从早期发现到临床研究阶段的生物学解决方案。药明康德测试业务平台可为包括血液肿瘤在内多个疾病领域的药物提供全生命周期的一体化研发测试服务及全方位的临床研究服务，助力合作伙伴的药物成功申报IND、NDA以及通过核查上市。随着对血液肿瘤发病机制理解的持续深化和治疗技术的不断创新，全球血液肿瘤药物研发正迈向更加精准、高效的新阶段。展望未来，药明康德将继续秉承“让天下没有难做的药，难治的病”的愿景，助力合作伙伴加速更多好药新药问世。参考资料： [1] Acute myelogenous leukemia，Retrieved september 9, 2025 from https://www.mayoclinic.org/diseases-conditions/acute-myelogenous-leukemia/symptoms-causes/syc-20369109 [2] Acute Myeloid Leukemia 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Retrieved september 9, 2025 from https://www.cancer.org/cancer/types/acute-myeloid-leukemia/about/key-statistics.html#:~:text=About%2022%2C010%20people%20will%20be,is%20about%20%C2%BD%20of%201%25. [6] Thomas X. First contributors in the history of leukemia. World J Hematol 2013; 2(3): 62-70 [DOI: 10.5315/wjh.v2.i3.62] [7] Kampen, Kim R. “The discovery and early understanding of leukemia.” Leukemia research vol. 36,1 (2012): 6-13. doi:10.1016/j.leukres.2011.09.028 [8] Strebhardt, K., Ullrich, A. Paul Ehrlich's magic bullet concept: 100 years of progress. Nat Rev Cancer 8, 473–480 (2008). https://doi-org.libproxy1.nus.edu.sg/10.1038/nrc2394 [9] The History of Leukemia. Retrieved september 9, 2025 from https://bloodcancerunited.org/resources/blog/history-leukemia#early-leukemia-discoveries [10] Blum S, Bacher U, Pabst T. 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[13] Stone, Richard M et al. “Midostaurin: its odyssey from discovery to approval for treating acute myeloid leukemia and advanced systemic mastocytosis.” Blood advances vol. 2,4 (2018): 444-453. doi:10.1182/bloodadvances.2017011080 [14] Acharya, Baku et al. “FLT3 inhibitors for acute myeloid leukemia: successes, defeats, and emerging paradigms.” RSC medicinal chemistry vol. 13,7 798-816. 23 May. 2022, doi:10.1039/d2md00067a [15] Daver, N., Schlenk, R.F., Russell, N.H. et al. Targeting FLT3 mutations in AML: review of current knowledge and evidence. Leukemia 33, 299–312 (2019). https://doi-org.libproxy1.nus.edu.sg/10.1038/s41375-018-0357-9 [16] Chowdhury, Rasheduzzaman et al. “The oncometabolite 2-hydroxyglutarate inhibits histone lysine demethylases.” EMBO reports vol. 12,5 (2011): 463-9. doi:10.1038/embor.2011.43 [17] Sun, X.-J.; Chen, Z.; Chen, S.-J. Mutations in DNA Methyltransferases and Demethylases. In Encyclopedia of Cancer, 3rd ed.; Boffetta, P., Hainaut, P., Eds.; Academic Press: Cambridge, MA, USA, 2019; pp. 528–537. [18] Mardis, Elaine R et al. “Recurring mutations found by sequencing an acute myeloid leukemia genome.” The New England journal of medicine vol. 361,11 (2009): 1058-66. doi:10.1056/NEJMoa0903840 [19] Issa, Ghayas C, and Courtney D DiNardo. “Acute myeloid leukemia with IDH1 and IDH2 mutations: 2021 treatment algorithm.” Blood cancer journal vol. 11,6 107. 3 Jun. 2021, doi:10.1038/s41408-021-00497-1 [20] Yun, Zhangjun, et al. "Global, Regional and National Burden of Leukemia, 1990-2021: Analysis of Data from the Global Burden of Disease Study 2021." Blood 144 (2024): 7907. 免责声明：本文仅作信息交流之目的，文中观点不代表药明康德立场，亦不代表药明康德支持或反对文中观点。本文也不是治疗方案推荐。如需获得治疗方案指导，请前往正规医院就诊。版权说明：欢迎个人转发至朋友圈，谢绝媒体或机构未经授权以任何形式转载至其他平台。转载授权请在「药明康德」微信公众号回复“转载”，获取转载须知。分享，点赞，在看，聚焦全球生物医药健康创新

免疫疗法细胞疗法抗体药物偶联物临床研究

2025-09-06

·梅斯医学

咳嗽、气喘半年以为是哮喘，结果血里“白细胞狂飙”，差点心脏衰竭！

35岁的王先生，半年多来一直咳嗽、气喘，还伴有反复皮疹。因为症状酷似哮喘，他在当地医院被诊断为“过敏性哮喘”，长期使用吸入药物和抗过敏药物。起初症状稍有缓解，但很快又反复发作。近两个月，王先生的病情急转直下：轻微活动就胸闷气短，晚上睡觉时还常常心悸出冷汗。家人以为是哮喘加重，催他再去复查。没想到，血常规结果让医生大吃一惊——嗜酸细胞数量高得离谱，是正常值的十几倍！进一步的骨髓活检和基因检测揭开了真相：王先生并不是单纯的哮喘，而是罕见的嗜酸细胞增多综合征（HES）。过量的嗜酸细胞像“不受控的白细胞军队”，已经大量浸润他的心脏和肺部，若不及时治疗，随时可能导致心衰甚至猝死。什么是高嗜酸粒细胞增多综合征（HES）高嗜酸粒细胞增多综合征（HES）又称特发性嗜酸粒细胞增多综合征（IHES）是一种病因不明的罕见疾病，其临床特征是嗜酸性粒细胞计数持续升高和嗜酸性粒细胞介导的器官损伤。最常见的症状是皮肤和呼吸道表现。HES可进一步引起胃肠道、心血管系统、神经系统和血液系统受累。目前估计患病率为每十万0.3到6.3之间。临床表现HES的临床表现复杂而缺乏特异性，几乎任何脏器均可受累，其中以心脏、皮肤、肺和神经系统最为常见。约一半患者在发病时即伴有心脏损害，主要表现为附壁血栓形成、纤维增生性心内膜炎以及左心室游离壁和室间隔的增厚，严重时可进展为充血性心力衰竭、心肌梗死，甚至出现广泛性心肌细胞坏死和凋亡，并伴随心律失常。心脏受累的程度往往与疾病的预后密切相关。皮肤受累可为首发表现，常见症状包括荨麻疹、瘙痒性红斑以及血管神经性水肿。肺部受累则以慢性干咳和呼吸困难为主，即便肺功能检查可能正常，影像学上也常见不典型浸润影。神经系统损害多累及周围神经系统，中枢神经系统受累较少见。胃肠道受累时，患者常表现为腹痛、腹泻、恶心和呕吐，主要波及胃、小肠及结肠，若病变累及肌层或浆膜层，可导致消化道梗阻或腹腔积液。血液系统方面可出现贫血、血小板减少和肝脾肿大。泌尿系统损害时，患者多有尿频、尿急、尿痛等尿路刺激症状，超声可提示膀胱壁增厚。除脏器受累外，患者还常有发热、乏力、消瘦和盗汗等全身症状，进一步增加了临床表现的多样性和复杂性。诊断HES诊断标准（WHO 2016）：①除外以下情况：反应性嗜酸粒细胞增多症；淋巴细胞变异型嗜酸粒细胞增多症（产生细胞因子，免疫表型异常的T细胞亚群）；CEL-NOS；WHO标准可确诊的髓系肿瘤（如MDS、MPN、MDS/MPN、AML）伴嗜酸粒细胞增多；伴有PDGFRA、PDGFRB、FGFR1重排或PCM1-JAK2嗜酸性粒细胞增多相关的MPN或AML/ALL。②嗜酸粒细胞绝对计数>1.5×109/L持续≥6个月，且必须有组织受损。如果没有组织受损，则诊断高嗜酸粒细胞增多症。治疗HES的治疗目标是降低嗜酸性粒细胞计数、预防或减轻器官损害。是否需要治疗、何时开始及如何选择方案取决于嗜酸性粒细胞水平、器官受累程度、病理机制及药物耐受性。皮质类固醇是首选药物，可快速降低嗜酸性粒细胞。羟基脲常作二线药物，适合与类固醇或干扰素-α联合应用。干扰素-α对部分难治病例有效，但副作用较多。酪氨酸激酶抑制剂（尤其是伊马替尼）是FIP1L1-PDGFRA阳性HES患者的首选一线方案，其余新型抑制剂仍在研究中。免疫调节剂如美泊利单抗、瑞斯珠单抗和阿仑珠单抗在部分患者中显示潜力，但应用仍有限。细胞毒性药物（如环磷酰胺、环孢素等）仅在难治病例中尝试。对常规治疗无效的重症患者，可考虑同种异体造血干细胞移植。总体而言，治疗需个体化，根据病因分型和器官受累情况选择合适方案，并权衡疗效与副作用。参考资料：Curtis C, Ogbogu P. Hypereosinophilic Syndrome. Clin Rev Allergy Immunol. 2016 Apr;50(2):240-51. doi: 10.1007/s12016-015-8506-7. PMID: 26475367.来源 | 梅斯医学编辑 | wanny神经系统罕见病交流群↓点击下方“阅读原文”，下载梅斯医学APP吧！

2025-09-03

·GlobeNewswire-Health Care

Step Pharma announces first participant dosed in a phase 1b clinical trial of dencatistat for essential thrombocythaemia

Start of the phase 1b trial in a new indication expands Step Pharma’s clinical programme, building on the development of dencatistat in lymphoma and solid tumours This milestone marks the third indication for dencatistat, a first-in-class, highly selective, orally available CTPS1 inhibitor, demonstrating its versatility as a "pipeline in a product" 2 September 2025 – Step Pharma (“the Company”), the global leader in CTPS1 inhibition for targeted cancer treatment, today announced that the first participant has been dosed with its lead asset dencatistat in a phase 1b clinical trial for essential thrombocythaemia (ET). ET is a rare clonal blood disorder in which the bone marrow produces too many platelets, increasing the risk of blood clots that can lead to serious thrombotic complications such as stroke or heart attack. Current treatments aim to lower platelet counts in order to reduce the risk of complications, but they can be associated with side effects or may not be suitable for all individuals, highlighting the need for more targeted therapies with improved safety profiles. Clinical trials of dencatistat in lymphoma have demonstrated that continual administration of dencatistat results in a dose dependent and reversible lowering of the platelet count. This finding (which has been mitigated by intermittent dosing for patients with lymphoma or solid tumours), along with the excellent tolerability profile of the drug, provides a strong rationale for investigating dencatistat as a treatment for ET. Andrew Parker, Chief Executive Officer of Step Pharma, commented: “Initiating the clinical evaluation of dencatistat in essential thrombocythaemia represents a significant milestone in our 'pipeline in a product' strategy. We believe we can harness selective CTPS1 inhibition to provide a safer, targeted approach to the treatment of ET. This expansion into a new indication, alongside our ongoing trials in lymphoma and solid tumours, further demonstrates the potential versatility of dencatistat as a targeted therapy. We look forward to collaborating with clinical investigators and those living with ET to advance this important programme.” The phase 1b open-label trial will evaluate the safety, tolerability, and preliminary activity of dencatistat in approximately 20 adult participants with high-risk ET who are resistant to, or intolerant of, hydroxycarbamide (hydroxyurea) therapy. The trial is being conducted at 12 sites across France and the UK. Andrew Parker, Chief Executive Officer of Step Pharma, commented: “Initiating the clinical evaluation of dencatistat in essential thrombocythaemia represents a significant milestone in our 'pipeline in a product' strategy. We believe we can harness selective CTPS1 inhibition to provide a safer, targeted approach to the treatment of ET. This expansion into a new indication, alongside our ongoing trials in lymphoma and solid tumours, further demonstrates the potential versatility of dencatistat as a targeted therapy. We look forward to collaborating with clinical investigators and those living with ET to advance this important programme.” Dencatistat (STP938) is a first-in-class, highly selective, orally bioavailable inhibitor of CTP synthase 1 (CTPS1), a key component of the pyrimidine synthesis pathway. CTPS1 inhibition blocks the proliferation of cancer cells and results in cell death. All cancers appear to be addicted to CTPS1 for DNA synthesis. Dencatistat entered clinical development in October 2022 for the treatment of T cell and B cell lymphoma and in September 2024 for the treatment of solid tumours. Dencatistat has the potential to become the backbone of treatment regimens for a broad range of haematological and solid tumours, as well as being a potent monotherapy for hard-to-treat blood cancers. Step Pharma’s goal is to bring about a step change in how cancer is treated with targeted therapies that kill cancer cells and leave healthy cells unharmed. The Company is the world leader in CTPS1 inhibition, a new approach with the potential to yield highly selective, safe and effective treatments for both blood cancers and solid tumours. Step Pharma was founded in 2014 by Kurma Partners, the Imagine Institute and Sygnature Discovery, based on the scientific discoveries of Prof. Alain Fischer and Dr Sylvain Latour. Step Pharma is based in Saint-Genis-Pouilly, France, and is supported by a strong syndicate of investors led by Kurma Partners and including Bpifrance (Fonds Biothérapies Innovantes et Maladies Rares and InnoBio2 Fund), Pontifax, Hadean Ventures, Sunstone Life Science Ventures, Inserm Transfert Initiative, Idinvest, Sygnature Discovery and the Imagine Institute. The content above comes from the network. if any infringement, please contact us to modify.

临床研究

100 项与羟基脲相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
D00341	羟基脲	L01XX05	DB01005

研发状态

批准上市

10 条最早获批的记录,

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适应症	国家/地区	公司	日期
真性红细胞增多症	日本	Clinigen KK	2013-03-25
真性红细胞增多症	日本	Bristol-Myers Squibb KK	2013-03-25
血管闭塞危机	欧盟	Theravia SAS	2007-06-29
血管闭塞危机	冰岛	Theravia SAS	2007-06-29
血管闭塞危机	列支敦士登	Theravia SAS	2007-06-29
血管闭塞危机	挪威	Theravia SAS	2007-06-29
慢性粒细胞性白血病	日本	CHEPLAPHARM Arzneimittel GmbH	1992-07-03
难治性慢性粒细胞白血病	日本	Clinigen KK	1992-07-03
原发性血小板增多症	日本	Clinigen KK	1992-07-03
头颈部肿瘤	中国	国药控股股份有限公司	1981-01-01
肾肿瘤	中国	国药控股股份有限公司	1981-01-01
黑色素瘤	中国	国药控股股份有限公司	1981-01-01
费城染色体阳性慢性粒细胞白血病	中国	国药控股股份有限公司	1981-01-01
头颈部鳞状细胞癌	中国	国药控股股份有限公司	1981-01-01
镰状细胞血症	美国	Waylis Therapeutics LLC	1967-12-07
疼痛	美国	Waylis Therapeutics LLC	1967-12-07

未上市

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
白蛋白尿	临床2期	科特迪瓦	Theravia SAS	2019-05-28
白蛋白尿	临床2期	法国	Theravia SAS	2019-05-28
白蛋白尿	临床2期	瓜德罗普	Theravia SAS	2019-05-28
白蛋白尿	临床2期	马里	Theravia SAS	2019-05-28
白蛋白尿	临床2期	马提尼克	Theravia SAS	2019-05-28
白蛋白尿	临床2期	塞内加尔	Theravia SAS	2019-05-28
β地中海贫血	临床2期	牙买加	Nova Laboratories Ltd.	2019-01-03
β地中海贫血	临床2期	英国	Nova Laboratories Ltd.	2019-01-03
血红蛋白SC疾病	临床2期	牙买加	Nova Laboratories Ltd.	2019-01-03
血红蛋白SC疾病	临床2期	英国	Nova Laboratories Ltd.	2019-01-03

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临床结果

适应症

分期

评价

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


ASCO2025	N/A	慢性粒单核细胞白血病一线	457	Hydroxyurea	艱鹽顧製構選襯鏇鹽繭(窪鹽齋鏇獵醖艱憲淵構) = 獵鹹遞繭製遞壓蓋獵衊蓋願淵鏇鏇鹹齋獵顧獵 (淵艱醖遞鹽壓膚衊選繭 ) 更多	积极	2025-05-30
				Hypomethylating agents (Azacitidine)	艱鹽顧製構選襯鏇鹽繭(窪鹽齋鏇獵醖艱憲淵構) = 淵顧選獵顧簾淵鏇網積蓋願淵鏇鏇鹹齋獵顧獵 (淵艱醖遞鹽壓膚衊選繭 )
NCT03806452 (SIKAMIC, CTgov)	临床2期	白蛋白尿 \| 镰状细胞血症	86	Hydroxycarbamide (Hydroxycarbamide)	膚壓選壓選選觸繭顧衊 = 簾鬱鹽築鑰艱願鹹遞構糧夢艱餘廠簾顧範願遞 (鹽觸壓夢觸鏇鬱構築構, 憲壓襯選鹹鏇憲衊艱獵 ~ 觸糧願壓繭構膚獵顧鏇) 更多	-	2025-05-14
				Placebo Oral Tablet (Placebo)	膚壓選壓選選觸繭顧衊 = 壓襯鏇襯積網鑰築繭襯糧夢艱餘廠簾顧範願遞 (鹽觸壓夢觸鏇鬱構築構, 製願鏇積鬱襯廠憲構鏇 ~ 選鏇顧糧窪構衊遞鏇繭) 更多
NCT03944915 (DEPEND, CTgov)	临床2期	乳头状瘤病毒感染 \| HPV相关鳞状细胞癌 \| 局部晚期头颈部鳞状细胞癌	35	Nivolumab+Carboplatin+Paclitaxel (Standard Chemotherapy)	淵鏇餘構積鏇築選憲蓋 = 餘餘襯築選鬱襯齋獵鏇築淵願構壓齋窪壓簾壓 (夢醖醖範繭窪製襯膚蓋, 製網繭選齋鏇蓋壓襯夢 ~ 憲艱壓鏇構壓顧壓鏇繭) 更多	-	2025-05-11
				Radiation+Filgrastim Injection+Paclitaxel+Hydroxyurea Pill+cisplatin+5-fluorouracil (De-escalated Chemotherapy)	淵鏇餘構積鏇築選憲蓋 = 膚構簾蓋膚餘廠夢選艱築淵願構壓齋窪壓簾壓 (夢醖醖範繭窪製襯膚蓋, 糧選網壓顧願繭鹹製築 ~ 衊糧憲構蓋憲積鬱簾齋) 更多
NCT03107182 (OPTIMA II \| OPTIMA-II, CTgov)	临床2期	头颈部鳞状细胞癌 \| HPV阳性的口咽鳞状细胞癌 \| HPV相关鳞状细胞癌 ... 更多	72	Adjuvant RT+Nivolumab (Single Modality De-escalation Arm (SDA))	淵艱齋齋淵積網壓積膚 = 觸鹽築範顧製簾壓鹽範築網遞衊遞壓網觸憲願 (繭壓鏇糧鬱製齋壓夢鑰, 繭醖憲鹹鹹醖餘窪鹹膚 ~ 範築淵鑰憲範積衊觸艱) 更多	-	2025-05-06
				Chemoradiotherapy+Nivolumab+Dexamethasone+Paclitaxel+hydroxyurea+cisplatin+Famotidine+Diphenhydramine+5-FU (Intermediate De-escalation Arm (IDA))	淵艱齋齋淵積網壓積膚 = 醖鏇廠鹹積顧廠齋繭範築網遞衊遞壓網觸憲願 (繭壓鏇糧鬱製齋壓夢鑰, 遞蓋壓餘構襯窪築鏇製 ~ 壓顧衊網衊齋構繭鏇鹹) 更多
NCT01966731 (REACH, ASH2024)	临床1/2期	镰状细胞血症	606	Hydroxyurea at MTD	築顧廠艱願築網顧鹹淵(艱繭範膚遞遞顧淵蓋構) = Two children contracted transfusion-acquired HIV, both of whom have continued hydroxyurea at MTD while concurrently receiving highly active antiretroviral treatment. 衊製顧襯範夢簾網製憲 (鹹網夢窪餘膚餘蓋顧壓 ) 更多	积极	2024-12-08
				Fixed-Dose Hydroxyurea
ASH2024	N/A	镰状细胞血症	-	Hydroxyurea	餘餘鹽淵構範鑰齋觸鑰(鏇鑰廠願蓋鑰襯糧願顧) = 繭膚廠壓製遞淵繭鹹顧簾膚繭範獵構餘餘窪壓 (範選範膚構鏇壓積願膚 ) 更多	-	2024-12-08
				Hydroxyurea (Control group)	餘餘鹽淵構範鑰齋觸鑰(鏇鑰廠願蓋鑰襯糧願顧) = 壓觸夢願襯憲齋簾積獵簾膚繭範獵構餘餘窪壓 (範選範膚構鏇壓積願膚 ) 更多
ASH2024	N/A	镰状细胞血症	-	Hydroxyurea	製繭鹽範衊膚齋範獵艱(範齋膚膚鹹鏇糧夢蓋壓) = forgetting to take medication (56.9%), cost (40.1%), non-availability due to stock issues (24%), problems with compounding medication (13.8%), medication fatigue (12%), feeling of wellness (12%), side effects (2.4%), and doubts about efficacy (1.2%) 鹽鏇壓繭膚壓廠構夢廠 (獵選觸醖艱選艱構餘顧 ) 更多	-	2024-12-08
NCT05662098 (ADAPT, ASH2024)	临床1期	镰状细胞血症	106	羟基脲	窪繭壓廠網壓壓鑰壓窪(遞鹹選襯壓選獵齋襯窪) = 艱鏇製築糧製壓夢餘憲醖築鹹簾簾鹽憲繭廠蓋 (範窪壓選艱鬱夢獵廠構 )	积极	2024-12-08
NCT03789591 (ASH2024)	临床3期	镰状细胞血症	-	Hydroxyurea (PK-guided dosing)	襯夢獵遞衊蓋鏇餘壓構(鹽簾膚遞築積廠簾築淵) = 網餘糧壓鬱願鏇糧夢鑰壓餘廠製鏇鬱觸餘觸鹽 (衊窪壓淵憲繭艱醖鑰簾 ) 更多	-	2024-12-07
				Hydroxyurea (Weight-based dosing)	構積衊鹽鏇衊壓膚製鹽(鹹獵簾壓築觸繭鬱鹽淵) = 選觸築鹽製淵淵簾蓋醖觸齋獵夢艱積獵憲廠構 (觸淵膚鹹範製廠鬱衊醖 ) 更多
ASH2024	N/A	镰状细胞血症	-	Hydroxyurea (Observation Arm)	製鹹衊憲艱獵蓋憲廠壓(蓋鏇齋醖膚鏇鹽選願積) = 齋襯淵醖鏇夢選鏇鑰願鬱醖艱衊襯廠觸淵鏇糧 (齋蓋鬱繭夢繭餘廠壓選 ) 更多	-	2024-12-07
				PK-guided hydroxyurea treatment	糧觸糧鹹鏇醖製衊衊構(積鹹襯願餘襯遞廠襯膚) = 願願壓艱顧製鏇餘願鏇積製網衊鬱簾憲憲獵積 (觸願鏇製鹽鹹獵蓋齋獵, 8.8) 更多