A Phase 1, Open Label, Dose Escalation Study Evaluating the Safety and Pharmacokinetics of Enteric Coated D-3263 Hydrochloride in Subjects With Advanced Solid Tumors

This is a Phase 1, dose escalation study evaluating safety and pharmacokinetics of enteric coated D-3263 HCl in subjects with advanced solid tumors

开始日期2009-03-01

申办/合作机构

Dendreon Corp.

100 项与 D-3263 相关的临床结果

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100 项与 D-3263 相关的转化医学

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100 项与 D-3263 相关的专利（医药）

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项与 D-3263 相关的文献（医药）

2024-11-01·LUTS-Lower Urinary Tract Symptoms

Transient Receptor Potential Melastatin 8 Contributes to Cystitis‐Induced Neuronal Sprouting and Pain Hypersensitivity Through AKT/mTOR Signaling Pathway in Interstitial Cystitis/Bladder Pain Syndrome

Article

作者: Zhang, Peng ; Chang, Ran ; Wu, Liyang

ABSTRACT:

Objectives:

The aim of this study was to investigate the mechanism of TRPM8 in neuroproliferation and pain, as well as the relevance of the Akt/mTOR signaling pathway in mice with IC/BPS.

Methods:

The model of IC/BPS was established in wild and TRPM8−/− mice. The mechanical sensitivity was measured. The number of neurite segments, length of neurites, and density of neurites were all counted. IL‐6 and norepinephrine levels were detected by ELISA, Western blot was used to detect protein levels of TRPM8, Akt, p‐Akt, mTOR, p‐mTOR. Immunofluorescence was used to detect TRPM8 expression and distribution in neurites, neurons, and sensory nerves in mouse bladder tissue.

Results:

Pain threshold in the IC/BPS group was decreased, and neurite segments, length, and density were all significantly enhanced when compared to the control group. The parameters in the IC/BPS model + Menthol group were more statistically significant. Neurite number and density were lower in TRPM8 knockout‐model mice than in IC/BPS model mice. The expression of TRPM8 and the ratios of p‐Akt/Akt and p‐mTOR/mTOR rose in the IC/BPS model group. In TRPM8 knockout‐model mice, the ratios of p‐Akt/Akt and p‐mTOR/mTOR were not substantially different from those in the control group. TRPM8 knockout‐model mice had considerably lower levels of serum IL‐6 and urine norepinephrine than IC/BPS model mice.

Conclusions:

TRPM8 can induce pain hypersensitivity and sensory nerve proliferation by activating Akt/mTOR pathway and raising the expression of IL‐6 and norepinephrine in IC/BPS models. These findings offer new perspectives on IC/BPS treatment.

Biomolecules3区 · 生物学

Trpm8 Expression in Human and Mouse Castration Resistant Prostate Adenocarcinoma Paves the Way for the Preclinical Development of TRPM8-Based Targeted Therapies

3区 · 生物学

ArticleOA

作者: Carbone, Francesco Giuseppe ; Lunardi, Andrea ; Alaimo, Alessandro ; Montironi, Rodolfo ; Genovesi, Sacha ; Vignoli, Beatrice ; De Felice, Dario ; Moro, Riccardo ; Barbareschi, Mattia ; Canossa, Marco

Metastatic prostate cancer (mPCa) is one of the leading causes of cancer-related mortality in both the US and Europe. Androgen deprivation is the first-line therapy for mPCa; however, resistance to therapy inevitably occurs and the disease progresses to the castration resistant stage, which is uncurable. A definition of novel targeted therapies is necessary for the establishment of innovative and more effective protocols of personalized oncology. We employed genetically engineered mouse models of PCa and human samples to characterize the expression of the TRPM8 cation channel in both hormone naïve and castration resistant tumors. We show that Trpm8 expression marks both indolent (Pten-null) and aggressive (Pten/Trp53 double-null and TRAMP) mouse prostate adenocarcinomas. Importantly, both mouse and human castration-resistant PCa preserve TRPM8 protein expression. Finally, we tested the effect of TRPM8 agonist D-3263 administration in combination with enzalutamide or docetaxel on the viability of aggressive mouse PCa cell lines. Our data demonstrate that D-3263 substantially enhances the pro-apoptotic activity of enzalutamide and docetaxel in TRAMP-C1 e TRAMP-C2 PCa cell lines. To conclude, this study provides the basis for pre-clinical in vivo testing of TRPM8 targeting as a novel strategy to implement the efficacy of standard-of-care treatments for advanced PCa.

BMC MICROBIOLOGY

Antibacterial activity and mechanisms of D-3263 against Staphylococcus aureus

Article

作者: Chen, Zhong ; Liu, Xiaoju ; Peng, Renhai ; Cai, Shuyu ; Wen, Zewen ; Xiong, Yanpeng ; Deng, Qiwen ; Yu, Zhijian ; Zhang, Yufang ; Hou, Tieying

Abstract:

Multi-drug-resistant Staphylococcus aureus infections necessitate novel antibiotic development. D-3263, a transient receptor potential melastatin member 8 (TRPM8) agonist, has potential antineoplastic properties. Here, we reported the antibacterial and antibiofilm activities of D-3263. Minimum inhibitory concentrations (MICs) against S. aureus, Enterococcus faecalis and E. faecium were ≤ 50 µM. D-3263 exhibited bactericidal effects against clinical methicillin-resistant S. aureus (MRSA) and E. faecalis strains at 4× MIC. Subinhibitory D-3263 concentrations effectively inhibited S. aureus and E. faecalis biofilms, with higher concentrations also clearing mature biofilms. Proteomic analysis revealed differential expression of 29 proteins under 1/2 × MIC D-3263, influencing amino acid biosynthesis and carbohydrate metabolism. Additionally, D-3263 enhanced membrane permeability of S. aureus and E. faecalis. Bacterial membrane phospholipids phosphatidylethanolamine (PE), phosphatidylglycerol (PG), and cardiolipin (CL) dose-dependently increased D-3263 MICs. Overall, our data suggested that D-3263 exhibited potent antibacterial and antibiofilm activities against S. aureus by targeting the cell membrane.

项与 D-3263 相关的新闻（医药）

2026-06-04

·BioSpace

Kallyope Presents New Data on Novel TRPM8 Channel Blocker Elismetrep for the Acute Treatment for Migraine at the American Headache Society 68th Annual Scientific Meeting

Results contribute to growing body of evidence in support of elismetrep, a TRPM8 migraine-associated channel blocker (MACB), to help address the debilitating impact of migraine Novel liquid-filled softgel capsule (LSGC) formulation results in earlier and more rapid absorption compared to the formulation used in Phase 2b Preclinical studies demonstrate additive efficacy with other migraine therapeutics including gepants and triptans Phase 3 studies anticipated to initiate in mid-2026 NEW YORK--(BUSINESS WIRE)--Kallyope is a late-stage biotechnology company focused on developing innovative migraine and metabolic disease therapies for health challenges faced by hundreds of millions of people globally. Today, the Company presented results from several clinical and preclinical studies that support the initiation of Phase 3 studies of elismetrep, a novel TRPM8 channel blocker. Elismetrep is a potentially new approach for migraine and the only agent known to be in late-stage development for the acute treatment of migraine. The data will be presented at the American Headache Society 68th Annual Scientific Meeting currently being held in Orlando, FL. Phase 3 studies of elismetrep for the acute treatment of migraine are anticipated to initiate mid-2026. “The opportunity to provide a new treatment for millions of people who suffer the debilitating effects of migraine is unique and important,” said Jay Galeota, CEO and President, Kallyope. “As the only late-stage therapeutic in development for the acute treatment of migraine, Kallyope has the responsibility of advancing elismetrep quickly and carefully to potentially bring a new opportunity for pain and symptom relief to the millions of people struggling with migraine symptoms, many of whom are forced to put their lives on hold at a moment’s notice.” Liquid-Filled Softgel Capsule Formulation Results in More Rapid Absorption which is Predicted to Improve Efficacy and Result in Earlier Onset of Pain Relief A Phase 1 biocomparison study compared the pharmacokinetics (PK) and safety/tolerability of a novel liquid-filled softgel capsule (LSGC) formulation of elismetrep to those of the dry-filled capsule (DFC) formulation used in the Phase 2b study. Elismetrep absorption was rapid and accelerated with the LSGC formulation (median time to maximum concentration [Tmax] = 1-h) compared to the DFC formulation (median Tmax = 2.5-h). While absorption was more rapid with the LSGC formulation, the overall extent of absorption was similar and there was no meaningful difference in tolerability between the two formulations. Exposure-response modeling and clinical trial simulations were used to estimate the impact of the new formulation on pain freedom and freedom from the most bothersome migraine-associated symptom. Model-based simulations with the PK data from the biocomparison study predicted ~50% and ~40% improvements in placebo-corrected response rates for 2-h pain freedom and 2-h freedom from the most bothersome symptom, respectively, as well as earlier onset of efficacy with the LSGC vs the DFC. “TRPM8 is a unique therapeutic target highly associated with migraine and currently not targeted by approved migraine treatments," said Peter J. Goadsby, MD, PhD, FRS, King Abdullah University of Science and Technology, Saudi Arabia. “With a unique mechanism of action and rapid absorption demonstrated by the liquid-filled softgel capsule formulation, elismetrep may provide much needed symptom relief to migraine patients who often have a narrow window to manage symptoms before debilitating symptoms take hold and force many to seek acute care.” Pre-Clinical Pro Elismetrep Supports Additive Efficacy in Combination with Other Mechanisms Single cell sequencing studies of human and rat trigeminal ganglia neurons show that TRPM8 is expressed in a distinct type of neuron from those expressing targets of other migraine therapeutics such as CALCA (CGRP), HRT1B/D , or HRT1F (serotonin receptor subtypes targeted by triptans and ditans). Elismetrep efficacy as monotherapy and in combination with gepants and triptans was evaluated in the well-established nitric oxide donor-induced facial allodynia rat model of migraine. The study demonstrated that the combination of sub-efficacious doses of elismetrep + olcegepant or elismetrep + sumatriptan showed additive efficacy whereas the combination of sub-efficacious doses of sumatriptan + olcegepant did not show additive efficacy. These findings suggest elismetrep has the potential to work in combination therapy with gepants or triptans. The company also presented results from the Phase 2b dose-ranging and proof of concept study of elismetrep (NCT06848075) previously shared at the 2026 American Academy of Neurology in an encore poster presentation. Elismetrep Profile “The five abstracts we are presenting at the 2026 American Headache Society meeting, including an encore of clinical data first presented at the 2026 American Academy of Neurology, collectively reinforce the differentiated potential of elismetrep as an investigational therapy for the acute treatment of migraine. Elismetrep's pro a highly selective TRPM8 blocker with favorable pharmacokinetics and promising efficacy support its potential as a novel migraine therapy,” said Brett Lauring, MD, PhD, Chief Medical Officer, Kallyope. Results from several Phase 1 studies (single- and multiple-ascending dose studies, a formulation biocomparison study, and a statin drug-drug interaction study) and in vitro profiling suggest that elismetrep has a good pro a novel migraine therapeutic. Elismetrep is a potent and selective inhibitor of TRPM8 with sub-nanomolar potency, is highly selective for TRPM8 vs other TRP channels, and had no meaningful off-target activities in standard screens against 81 receptors, enzymes, and ion channels. Elismetrep has been safe and well tolerated in 13 completed clinical studies with 1,055 people exposed to at least one dose and with single doses up to 900 mg and multiple doses up to 400 mg QD evaluated. In humans, absorption is rapid with the new LSGC formulation (median Tmax = 1-h). The pharmacokinetics are dose proportional up to 900 mg, and food has no meaningful impact on absorption, meaning elismetrep can be taken without regard to food. The half-life is long and ranged from 11-21-h following single doses. Multiple doses of elismetrep 150 mg had no clinically meaningful effect on the PK of rosuvastatin and simvastatin (CYP3A4 and OATP1B1 substrates) which together with in vitro profiling against other CYP isoforms and transporters all suggest a low risk of elismetrep perpetrating drug-drug interactions. Because elismetrep is metabolized by multiple pathways, there is a low risk for drug-drug interactions. About Transient Receptor Potential Melastatin 8 (TRPM8) Migraine is increasingly understood as a disorder of trigeminal sensory neuron hyperexcitability, in which trigeminal sensory pathways become sensitized, leading to sensory hypersensitivity and amplified pain signaling. TRPM8 is a polymodal gated ion channel expressed on a distinct subset of trigeminal neurons relevant to migraine pain signaling. In the context of migraine, TRPM8 activity is associated with trigeminal sensory neuron pathway activation, contributing to pain onset and heightened, sustained pain signaling. TRPM8 is a mechanistically distinct therapeutic target from current migraine treatments, including calcitonin gene-related peptide (CGRP) receptor antagonists and serotonin receptor-based agents, and is the only TRP channel with an established genetic association to migraine in genome-wide association studies. About Elismetrep Elismetrep (K-304) is an investigational, novel, oral, TRPM8 migraine-associated channel blocker (MACB) that is highly selective for TRPM8 migraine-associated channels vs. other TRP channels. Specifically designed to block TRPM8 activity, elismetrep has been shown to reduce migraine pain and associated symptoms. The Phase 2b dose-ranging and proof of concept trial for elismetrep for the acute treatment of migraine in adults demonstrated clinically meaningful efficacy that was competitive with current leading marketed therapies. No safety signals were observed. Elismetrep was well tolerated, and the large majority of reported adverse events were mild. Phase 3 trials for elismetrep for the acute treatment of migraine are planned to initiate in mid-2026. Elismetrep is an investigational product and has not been approved by the FDA or any other regulatory agency. About Kallyope Kallyope is a late-stage biotechnology company focused on developing innovative migraine and metabolic therapies for health challenges faced by hundreds of millions of people globally. Kallyope’s lead programs target previously unknown drivers of disease in neural signaling pathways. The Company’s most advanced candidate, elismetrep (K-304), is poised to begin Phase 3 trials for the acute treatment of migraine in mid-2026. The metabolism pipeline includes agents that target a novel target identified and validated by the Company’s Klarity™ platform, as well as oral small molecule approaches to the highly validated amylin pathway for the treatment of obesity. Kallyope was founded by world-leading neuroscientists and continues to explore the role of neural circuits in driving disease. For more information, visit . Contacts Media Contact: Ten Bridge Communications Michael Galfetti TBCKallyope@tenbridgecommunications.com Investor Contact: Kallyope ir@kallyope.com

2026-05-20

·药学进展

独家原创 | 交泰丸调控胰腺5-羟色胺系统改善胰岛β细胞功能的机制研究

“ 点击蓝字关注我们交泰丸调控胰腺5-羟色胺系统改善胰岛β细胞功能的机制研究 PPS 曹雯1#，赵一璟1，2#，陈煜2，杨昱1，王苏1，陈堃1，王昆1* （1. 南京医科大学附属江宁医院内分泌科，江苏南京211100；2. 南京中医药大学附属中西医结合医院内分泌实验室，江苏南京210028） [摘要] 背景胰岛β细胞功能损伤是2型糖尿病（type2 diabetes mellitus ，T2DM）的主要病理机制之一。胰岛β细胞自身分泌的血清素[5-羟色胺（5-hydroxytryptamine ，5-HT）]在葡萄糖刺激下能够增加胰岛β细胞数量并促进胰岛素分泌。交泰丸（Jiao-Tai-Wan， JTW）是一种具有降糖功效的传统中药方剂。然而，JTW是否通过调控胰腺5-HT系统改善胰岛β细胞功能损伤，目前尚不明确。目的探究JTW在db/db小鼠中的降糖作用及其具体分子机制。方法制备JTW溶液，采用高效液相色谱法鉴定其主要活性成分。将所有db/db小鼠随机分为5组，每组8只，分别为：糖尿病模型组（Mod组，灌胃等体积蒸馏水）、二甲双胍组（Met组，灌胃剂量0.25g·kg-1·d-1）、交泰丸低剂量组（JTWL组，灌胃剂量2.1g·kg-1·d-1）、交泰丸中剂量组（JTWM组，灌胃剂量4.2g·kg-1·d-1）和交泰丸高剂量组（JTWH组，灌胃剂量8.4g·kg-1·d-1）。实验周期为6周，每周测量小鼠体重和空腹血糖（fasting plasma glucose ，FPG），6周后内眦取血后脱颈处死小鼠。通过苏木素-伊红染色评估胰腺组织形态，采用酶联免疫吸附分析（enzyme-linked immunosorbent assay ，ELISA）检测各组小鼠血清胰岛素表达水平，采用定量逆转录聚合酶链反应（quantitative reverse transcription polymerase chain reaction ，qRT-PCR）检测胰腺组织中Ins1和Ins2的信使核糖核酸（messenger RNA ，mRNA）表达水平。采用ELISA、qRT-PCR、免疫荧光或免疫组化方法，评估胰腺5-HT系统相关指标的表达情况，包括5-HT、5-羟色胺受体2B（5-hydroxytryptamine receptor 2B， 5-HTR2B ）和瞬时受体电位锚蛋白1（transient receptor potential ankyrin 1 ，TRPA 1）。结果 JTW可降低db/db小鼠的FPG水平，但对其体重无显著影响。同时，JTW可改善db/db小鼠的胰岛细胞形态结构，升高血清胰岛素浓度，上调胰腺组织中Ins1和Ins2的mRNA表达水平。此外，JTW还可上调db/db小鼠胰腺组织中5-HT、5-HTR2B和TRPA1的表达。结论 JTW可通过调控胰腺5-HT系统改善胰岛β细胞功能，为阐明JTW治疗T2DM的具体分子机制提供了新的研究思路。 2型糖尿病（type 2 diabetes mellitus ，T2DM）是一种慢性代谢性疾病，发病机制复杂，胰岛β细胞功能障碍是其主要病理机制之一。胰岛β细胞功能障碍可导致胰岛素分泌不足，进而引发血糖升高，但其具体调控机制目前尚不完全明确。5-羟色胺（5-hydroxytryptamine ，5-HT）作为一种单胺类物质，具有多种生物学活性，需通过与不同亚型的5-羟色胺受体（5-hydroxytryptamine receptors ，5-HTRs）结合发挥生物学作用[1]。传统研究中，5-HT主要作为神经递质，在中枢神经系统疾病领域被广泛探讨。最近研究表明[2]，5-HT可诱导α细胞向β细胞转化。在葡萄糖刺激条件下，胰岛β细胞也可自主合成并分泌5-HT[3]，且该过程可进一步促进胰岛β细胞增殖和胰岛素分泌。基于上述研究推测，促进胰岛β细胞分泌5-HT并上调胰岛β细胞表面5-HTRs表达，可能是促进胰岛β细胞增殖、增加胰岛素分泌和改善血糖代谢的重要途径。交泰丸（Jiao-Tai-Wan ，JTW）是一味经典中药方剂，由黄连和肉桂配伍组成，首载于中医典籍《韩氏医通》。其传统治则为交通心肾，临床常用于治疗心火亢盛证和心肾不交证。传统应用中，JTW多用于治疗失眠、认知障碍和抑郁[4-5]；近期研究发现，JTW可通过上调中枢神经系统内5-HT水平发挥镇静催眠作用，从而改善失眠症状[6]。与此同时，大量临床研究证实，JTW具有显著降糖效应，其作用机制与改善胰岛β细胞功能和降低胰岛素抵抗密切相关[7-8]。然而，JTW是否通过调控胰腺5-HT系统，进而改善胰岛β细胞功能，目前尚未明确。本研究采用db/db小鼠进行体内实验，探究JTW是否通过促进胰岛β细胞产生5-HT、上调胰岛β细胞5-HTRs表达来改善胰岛β细胞功能，为阐明JTW治疗T2DM的具体分子机制提供实验依据与理论支撑。 1 材料和方法 1.1 药材与试剂黄连（亳州市万珍中药饮片厂，产地：重庆石柱，规格：统货）和肉桂（贵州同德药业股份有限公司，产地：广西，规格：选丝）均购自江苏省中西医结合医院。所有药材均依据《中华人民共和国药典》（2020版）进行形态学鉴定。中药单体对照品包括表小檗碱、盐酸黄连碱、盐酸小檗碱、盐酸药根碱、4-羟基-3-甲氧基肉桂醛、松柏醛、肉桂醛和肉桂醇，购自拓普科学有限公司（中国）。二甲双胍片（中美上海施贵宝制药有限公司，国药准字H20023370，规格：500mg/片）购自江苏省中西医结合医院。胰岛素、5-HT、5-羟色胺受体2B（5-hydroxytryptamine receptor 2B ，5-HTR2B）和瞬时受体电位锚蛋白1（transient receptor potential ankyrin 1，TRPA 1）相关抗体均购自CST公司（德国）。5-HT和胰岛素酶联免疫吸附分析（enzyme-linked immu- nosorbent assay ，ELISA）试剂盒均购自R&D系统公司（美国）。cDNA逆转录试剂盒和SYBR Green Master Mix试剂购自应用生物系统公司（美国）。TRIzol试剂购自Invitrogen公司（美国）。 1.2 JTW制备取黄连30g、肉桂3g，溶于80mL双蒸馏水中，制成质量浓度为0.42g·mL-1的药液，置于4℃冰箱冷藏保存，备用。 1.3 JTW化合物检测采用高效液相色谱法（high performance liquid chromatography ， HPLC）对JTW溶液进行成分分析，明确方剂中的主要化学成分。使用的对照品包括：盐酸黄连碱、表小檗碱、盐酸小檗碱、盐酸药根碱、4-羟基-3-甲氧基肉桂醛、松柏醛、肉桂醛和肉桂醇。HPLC分析采用UPLC BEH C18柱（2.1mm×100mm，1.7μm，Waters公司，美国）；流动相由0.1%甲酸水溶液（A）和0.1%甲酸乙腈溶液（B）组成。洗脱梯度采用多级线性洗脱程序，具体如下：0~11min，85%~25%A；11~12min，25%~2%A；12~14min，2%A；14~14.1min，2%~85%A；14.1~16min，85%A。样品进样量设定为5μL，流速设定为0.5mL·min-1。 1.4 动物喂养和分组 5周龄雄性db/db小鼠40只（体重26~30g）购自江苏集萃药康生物科技有限公司（中国），饲养于江苏省中西医结合医院实验动物中心，研究时间为2023年6月至12月。小鼠分笼饲养，研究期间所有小鼠均不限制饮水和食物，室温（25±2）℃,相对湿度为50%~70%，通风性良好，12h交替照明。动物实验方案经江苏省中西医结合医院实验动物伦理委员会审查批准（伦理编号：AEWC-20230608-313），并遵循实验动物相关管理与保护准则。所有db/db小鼠均喂养普通饲料（脂肪提供10%热量），喂养3周后，采用随机数字表法分为5组（每组8只），分别为糖尿病模型组（Mod组）、二甲双胍组（Met组）、交泰丸低剂量组（JTWL组）、交泰丸中剂量组（JTWM组）和交泰丸高剂量组（JTWH组）。各组小鼠每日灌胃干预1次，Mod组给予同体积蒸馏水，Met组给予二甲双胍（0.25g·kg-1·d-1），JTWL组、JTWM组、JTWH组分别给予低、中、高剂量JTW（剂量分别为2.1、4.2、8.4g·kg-1·d-1），灌胃干预持续6周。 1.5 体重和空腹血糖（fasting plasma glucose， FPG）的测定实验期间每2周测量1次体重，同时通过尾静脉采血检测FPG水平。 1.6 血液及组织标本的留取灌胃干预6周后，对所有小鼠采用内眦取血法采血，采血完毕后脱颈处死。所取血液于4℃条件下以3 000r·min-1转速离心10min，收集血清上清，置于－80℃冰箱保存待测。小鼠处死后，迅速剖开腹腔，摘取胰腺组织，用4℃生理盐水润洗。取部分胰腺组织置于标本冻存管中，－80℃冰箱保存待用；剩余胰腺组织用4%多聚甲醛溶液固定，用于病理形态学检测。 1.7 血清学指标检测血清胰岛素和5-HT水平均采用ELISA法测定。 1.8 胰腺组织苏木素-伊红（hematoxylin-eosin， HE）染色胰腺组织用4%多聚甲醛溶液固定，石蜡包埋后切成4μm厚切片；二甲苯脱蜡，梯度乙醇脱水，HE染色；染色完成后，梯度乙醇脱水，封片，于显微镜下观察胰腺组织形态并拍照留存。 1.9 免疫组化和免疫荧光检测取石蜡包埋的胰腺组织，连续切成4μm厚切片，分别用于免疫荧光和免疫组化染色。免疫荧光染色使用5-HT抗体（大鼠来源，ImmunoStar公司，稀释比例1∶500）和胰岛素抗体（兔来源，Dako公司，稀释比例1∶500）。免疫组化染色使用5-HTR2B抗体（兔来源，Alomone公司，稀释比例1∶1 000）和TRPA1抗体（豚鼠来源，Abcam公司，稀释比例1∶500）。 1.10 胰腺组织相关基因表达检测使用TRIzol试剂提取胰腺组织总RNA，测定RNA浓度和纯度并进行逆转录反应。定量逆转录聚合酶链反应（quantitative reverse transcription poly- merase chain reaction ，qRT-PCR）的反应程序设置如下：95℃预变性10min；随后进行40个循环的扩增反应（95℃变性10s，60℃退火与延伸60s）；循环结束后进行熔解曲线分析（95℃保温15s，60℃缓慢升温至95℃)。使用相对定量2-ΔΔCt法计算各目标基因信使核糖核酸（messenger RNA，mRNA）的相对表达水平。使用的基因引物序列如表1所示。 1.11 统计分析所有实验数据均以均值±标准差表示。2组比较采用t检验；多组比较采用单因素方差分析；多组组间比较时，方差齐性采用LSD检验，方差不齐采用Tamhane,s检验；小鼠FPG水平及体重同时采用重复测量方差分析进行比较。分析使用GraphPad Prism 7软件完成。P＜0.05被视为差异具有统计学意义，分别用*P＜0.05和**P＜0.01表示。 2 结果 2.1 HPLC法鉴定JTW中的化合物《中华人民共和国药典》（2020年版）中界定JTW组成的对照品包括以下化合物：盐酸黄连碱、盐酸小檗碱、表小檗碱、盐酸药根碱、4-羟基-3-甲氧基肉桂醛、松柏醛、肉桂醛和肉桂醇。采用HPLC法对JTW药液进行成分鉴定，通过与对照品比较，鉴定出JTW溶液中含有的上述8种化合物（见图1），该结果与既往相关研究结果基本一致[9]。 2.2 JTW对db/db小JTW对db/db小鼠体重和FPG水平的影响本研究观察了JTW对db/db小鼠体重的影响，结果显示，JTW各剂量组对db/db小鼠体重无显著影响（见图2A）。对4个时间点的小鼠体重数据进行重复测量方差分析，结果显示：时间主效应显著（F=12.295，P=0.001），提示不同测量时间点小鼠体重的总体均值存在统计学差异；时间与分组的交互作用不显著（F=0.816，P=0.535），表明各组小鼠体重随时间的变化趋势一致。此外，主体间效应检验显示，不同分组间小鼠体重的平均值无显著差异（F=0.545，P=0.704）。与体重变化不同，JTW能够显著降低db/db小鼠的FPG水平，且该降糖作用呈剂量依赖性，其中JTWH组的降糖效果最为显著（见图2B）。对4个时间点的小鼠FPG数据进行重复测量方差分析，结果显示：时间主效应不显著（F=0.605，P=0.574），提示不同时间点小鼠FPG测量值无统计学差异；时间与分组的交互作用不显著（F=1.142，P=0.352）。此外，主体间效应检验显示，不同分组间小鼠FPG的平均值存在显著差异（F=2.957，P=0.043）。 2.3 JTW对db/db小JTW对db/db小鼠体重和FPG水平的影响胰腺组织HE染色结果显示，Mod组db/db小鼠胰腺组织中，胰岛体积缩小、边界模糊、形状不规则，胰岛内细胞数量显著减少，细胞形态异常且排列稀疏。与Mod组相比，JTW各剂量组和Met组小鼠的胰岛数量增多、体积增大，且胰岛内细胞排列更规整，胞质含量更丰富，胰腺组织病理损伤得到明显改善（见图3）。血清学检测结果显示，与Mod组相比，JTWL组、JTWM组、JTWH组db/db小鼠的血清胰岛素水平显著升高（均P＜0.05），而Met组对血清胰岛素水平的影响较小，差异无统计学意义（P＞0.05），具体数据见表2。同时，JTWL组、JTWM组、JTWH组胰腺组织中Ins1和Ins2的mRNA相对表达水平均显著高于Mod组（P＜0.05或P＜0.01），具体数据见表2。 2.4 血清5-HT质量浓度的变化血清ELISA检测结果显示，JTWM组、JTWH组db/db小鼠血清5-HT质量浓度显著高于Mod组（P＜0.05或P＜0.01），而Met组和JTWL组小鼠血清5-HT质量浓度与Mod组相比，差异无统计学意义（P＞0.05），具体数据见表2。 2.5 胰腺组织中5-HT表达的变化免疫荧光染色结果显示，与Mod组和Met组相比，JTW各剂量组胰腺组织中5-HT阳性染色面积占比增加（见图4）。该结果表提示，JTW可上调胰腺组织中5-HT的表达水平。 2.6 胰腺组织中5-HTR2B表达的变化免疫组化染色结果显示，与Mod组和Met组相比，JTW各剂量组胰腺组织中5-HTR2B阳性染色面积占比明显增加（见图5）。qRT-PCR检测结果进一步证实，JTWL组、JTWM组、JTWH组胰腺组织中Htr2b的mRNA相对表达水平显著高于Mod组（P＜0.05），具体数据见表2。 2.7 胰腺组织中TRPA1表达的变化免疫组化染色结果显示，与Mod组和Met组相比，JTW各剂量组胰腺组织中TRPA1阳性染色面积占比增加（见图6）。qRT-PCR检测结果与之相符，JTWL组、JTWM组、JTWH组胰腺组织中Trpa1的mRNA相对表达水平显著高于Mod组（均P＜0.05），具体数据见表2。 3 讨论目前，T2DM的主要治疗手段是口服降糖药物和胰岛素注射治疗，但此类治疗方案仍存在肝功能异常、低血糖和胃肠道不适等潜在不良反应，临床应用存在一定局限性。传统中医药在T2DM的预防和治疗中展现出独特的潜在优势。近年来临床和动物实验研究均证实，JTW具有显著降糖作用[7-8]，与本研究结果一致。本研究中JTW以剂量依赖方式降低db/db小鼠FPG水平，并能明显改善糖尿病小鼠胰岛细胞的形态结构。而二甲双胍仅有降糖效果，不能促进胰岛素分泌及改善胰岛形态，这是由二甲双胍作用机制决定的，其通过改善胰岛素敏感性、减少肝糖输出来降低血糖，并抑制胰岛素分泌。此外，本研究未发现JTW和二甲双胍对db/db小鼠体重产生显著影响，提示2种药物具有较好的用药安全性。已有研究报道，JTW可改善胰岛β细胞功能并降低胰岛素抵抗[7]，其组方中的黄连、肉桂及从中提取的中药单体均具有促进胰岛β细胞功能完善和增殖的作用[10-11]，本研究结果进一步佐证了这一结论：经JTW治疗后，糖尿病小鼠血清胰岛素浓度显著升高，胰腺组织中Ins1和Ins2的mRNA相对表达水平明显上调，提示JTW可通过促进胰岛素合成与分泌，改善胰岛β细胞功能。既往研究证实，胰岛β细胞在葡萄糖刺激下可合成并分泌5-HT，而5-HT通过与5-HTRs结合后能够促进胰岛素分泌，这也为进一步探究中医药通过调控胰腺5-HT系统治疗T2DM提供了重要研究思路。已有报道显示，JTW可调节中枢神经系统中的5-HT水平[6]，但该方剂是否能调控胰腺组织中5-HT的产生与分泌，目前尚未明确。本研究发现，JTW干预可显著改善糖尿病小鼠的胰岛素分泌功能，同时能促进胰腺组织中5-HT的表达，并提高血清5-HT质量浓度，提示JTW改善胰岛β细胞功能的作用，可能与上调胰腺5-HT的产生及分泌密切相关。 5-HTRs多属于G蛋白偶联受体家族，5-HT通过与不同亚型的5-HTRs结合发挥不同作用[12]。在5-HTRs中，5-HTR2B被证实与5-HT介导的胰岛β细胞增殖和胰岛素分泌改善相关。一项研究表明，哺乳期间，胰岛β细胞中Htr2b的表达水平显著升高，且与胰岛β细胞数量增加、功能改善呈正相关[3]。黄连作为JTW的主要组方药材，已被证实可促进胰岛β细胞产生胰岛素，但其具体机制尚未完全明确[13]。另有研究显示，黄连提取物中的小檗碱能够激活神经元突触前5-HTR1A并抑制突触后5-HTR1A和5-HTR2的表达，提示小檗碱能够特异性调控不同细胞中5-HTRs的表达[14]。然而，目前尚未有研究探讨黄连对胰岛β细胞中5-HTRs的调控作用。本研究发现，JTW干预能够上调胰腺组织中5-HTR2B的蛋白及mRNA表达水平，并同步促进胰岛素分泌，提示Htr2b可能参与JTW改善胰岛β细胞功能的调控过程，但具体机制尚不清楚。 TRPA1是一种非选择性阳离子通道，可通过介导钙离子内流促进细胞内相关物质的释放。TRPA1广泛分布于胃肠道组织，同时也在胰岛β细胞中表达[15]。已有研究证实，TRPA1通道的激活剂可导致胰岛β细胞膜去极化并产生动作电位，从而促进胰岛素分泌，且该效应可被选择性TRPA1抑制剂阻断[16]。此外，肉桂醛作为一种特异性TRPA1激动剂，可通过激活TRPA1通道，以剂量依赖方式促进细胞释放5-HT[17]。另有研究发现，低剂量肉桂醛可上调血清胰岛素水平[18]。肉桂作为JTW的另一重要组方药材，其主要有效成分肉桂醛可能通过调控TRPA1通道发挥作用。本研究结果显示，JTW干预后，胰腺组织中TRPA1的蛋白及mRNA表达水平显著升高，初步证实JTW可通过激活胰腺组织中的TRPA1，促进5-HT产生，进而介导胰岛素释放，这为阐明JTW调控胰腺5-HT系统的具体通路提供了重要线索。然而，5-HT如何进一步促进胰岛β细胞增殖和胰岛素分泌，其详细分子机制仍需后续研究深入探究。本研究初步证实，JTW可通过激活胰腺组织TRPA1促进5-HT的产生与分泌，并上调胰腺组织中5-HTR2B的表达，进而促进胰岛素合成与分泌，最终改善胰岛β细胞功能。但本研究仍存在一定局限性：首先，本研究仅开展了体内动物实验，上述调控机制的具体细节仍需通过体外细胞实验进一步验证；其次，胰腺细胞中还表达其他亚型的5-HTRs，这些受体是否参与JTW介导的胰岛β细胞功能改善，其作用及调控关系仍需进一步探究。 4 结论本研究初步证实，JTW可通过调控胰腺5-HT系统改善db/db小鼠胰岛β细胞功能、促进胰岛素分泌、降低FPG水平，为阐明JTW治疗T2DM的具体分子机制提供了新的见解。参考文献： [1] Wang H, Gu Y, Khalid R, et al. Herbal medicines for insomnia through regulating 5-hydroxytryptamine receptors: a syste- matic review[J]. Chin J Nat Med, 2023, 21(7): 483-498. [2] Liu N, Liu T, Alim N, et al. 5-HT promotes pancreatic α-to-β cell transdifferentiation[J]. Biochim Biophys Acta Mol Cell Res, 2025, 1872(5): 119958. [3] Goyvaerts L, Schraenen A, Lemaire K,et al. Normal pregnancy-induced islet beta cell proliferation in mouse models that are deficient in serotonin-signaling[J]. Int J Mol Sci, 2022, 23(24): 15816. [4] Xia N, Jiang C, Zhou Y, et al. A double-blind, randomized, placebo-controlled, single-center clinical trial of jiaotaiwan for the treatment of insomnia symptoms caused by disharmony of the heart and kidney[J]. Front Pharmacol, 2022, 13: 1011003. [5] 王妍, 阮毓卿, 崔璨, 等 . 交泰丸通过激活 PI3K/AKT 信号通路改善阿尔茨海默病模型小鼠大脑的葡萄糖代谢[J]. 南方医科大学学报, 2024, 44(5): 894-903. [6] 石晓雨, 陈丽萍, 李文斌, 等 . 经典名方防治失眠的研究进展[J]. 中南大学学报(医学版), 2023, 48(10): 1494-1505. [7] Chen X, Yang Z, Du L, et al. Study on the active ingredients and mechanism of action of Jiaotai Pill in the treatment of type 2 diabetes based on network pharmacology: a review[J]. Medicine, 2023, 102(13): e33317. [8] Tang Y, Su H, Wang H, et al. The effect and mechanism of Jiao-Tai-Wan in the treatment of diabetes mellitus with depression based on network pharmacology and experimental analysis[J]. Mol Med, 2021, 27(1): 154. [9] 陈佩瑶 , 戴国梁 , 王艳军 , 等 . 交泰丸入脑成分通过 PTEN/ AKT/NF-κB通路抑制 LPS 诱导 BV2 细胞炎症的机制研究[J]. 中国医院药学杂志, 2025, 45(6): 614-621. [10] Yu C, Qiu Y, Yan D, et al. Berberine treatment inhibits ferroptosis in NIT-1 murine pancreatic cell line via inhibiting OGT expression levels[J]. Sci Rep, 2025, 15(1): 18504. [11] Li W, Qiao J, Lin K, et al. Ethyl-acetate fraction from a cinnamon-cortex extract protects pancreatic β -cells from oxi- dative stress damage[J]. Front Pharmacol, 2023, 14: 1111860. [12] Cummins B R, Billac G B, Nichols D E, et al. 5-HT2A receptors: pharmacology and functional selectivity[J]. Pharmacol Rev, 2025, 77(4): 100059. [13] 陈可, 张效科 . 中药黄连治疗 2 型糖尿病药理机制研究进展[J]. 辽宁中医药大学学报, 2025, 27(2): 94-98. [14] Vaishnav V A D, Patel R, Maturkar V, et al. Berberine-induced behavioral effects on tail suspension test, BDNF, and CREB levels in the prefrontal cortex, hippocampus, and amygdala: modulation by central serotonergic transmission[J]. Synapse, 2025, 79(5): e70028. [15] KudsiSQ, Piccoli B C, Ardisson-AraújoD,et al. Transcriptional landscape of TRPV 1, TRPA 1, TRPV4, and TRPM8 channels throughout human tissues[J]. Life Sci, 2022, 308: 120977. [16] Islam M S. Molecular regulations and functions of the transient receptor potential channels of the islets of Langerhans and insulinoma cells[J]. Cells, 2020, 9(3): 685. [17] Lieder B, Hoi J, Burian N, et al. Structure-dependent effects of cinnamaldehyde derivativeson TRPA 1-inducedserotonin release in human intestinal cell models[J]. JAgric Food Chem, 2020, 68(13): 3924-3932. [18] 褚鹿鹿, 郭智慧, 侯婧悦, 等 . 肉桂醛防治糖尿病的药理作用研究进展[J]. 现代药物与临床, 2023, 38(2): 483-487. 本文引文格式：曹雯, 赵一璟, 陈煜, 等. 交泰丸调控胰腺5-羟色胺系统改善胰岛β细胞功能的机制研究[J]. 药学进展, 2026, 50(01): 35-41. 美编排版：杨书惠感谢您阅读《药学进展》微信平台原创好文，也欢迎各位读者转载、引用。本文选自《药学进展》2026年第 1 期。《药学进展》杂志由教育部主管、中国药科大学主办，中国科技核心期刊（中国科技论文统计源期刊）。刊物以反映药学科研领域的新方法、新成果、新进展、新趋势为宗旨，以综述、评述、行业发展报告为特色，以药学学科进展、技术进展、新药研发各环节技术信息为重点，是一本专注于医药科技前沿与产业动态的专业媒体。《药学进展》注重内容策划、加强组稿约稿、深度挖掘、分析药学信息资源、在药学学科进展、科研思路方法、靶点机制探讨、新药研发报告、临床用药分析、国际医药前沿等方面初具特色；特别是医药信息内容以科学前沿与国家战略需求相合，更加突出前瞻性、权威性、时效性、新颖性、系统性、实战性。根据最新统计数据，刊物篇均下载率连续三年蝉联我国医药期刊榜首，复合影响因子1.311，具有较高的影响力。《药学进展》编委会由国家重大专项化学药总师陈凯先院士担任主编，编委由新药研发技术链政府监管部门、高校科研院所、制药企业、临床医院、CRO、金融资本及知识产权相关机构近两百位极具影响力的专家组成。联系《药学进展》↓↓↓ 编辑部官网：pps.cpu.edu.cn；邮箱：yxjz@163.com；电话：025-83271227。欢迎投稿、订阅！往期推荐聚焦“第七届药学前沿学术论坛暨《药学进展》编委会会议” 聚力前沿赛道，共启学术新程：第七届药学前沿学术论坛在南京隆重启幕承学术匠心，启时代新章：《药学进展》第七届编委会、第三届青年编委会成立大会在宁召开聚焦“兴药为民·2023生物医药创新融合发展大会”“兴药为民·2023生物医药创新融合发展大会”盛大启幕！院士专家齐聚杭城，绘就生物医药前沿赛道新蓝图“兴药强刊”青年学者论坛暨《药学进展》第二届青年编委会议成功召开“兴药为民·2023生物医药创新融合发展大会”路演专场圆满收官！校企合作新旅程已启航我知道你在看哟

2026-04-22

·酷炫z

2025年美国FDA批准新药简析

前言：这几天美国加州宜居城市圣地亚哥正在热闹召开美国癌症研究协会（AACR）2026年度会议，各路大咖纷纷到场。AACR每年发布的前沿成果，尤其是关于新靶点发现、临床前研究数据和早期临床数据，预示了未来癌症治疗的发展方向。AACR年会不仅是全球肿瘤研究领域的权威学术盛会，更是新药审批和临床研发的风向标。圣地亚哥是全球三大生命科学中心之一，在生物技术集中度、资金投入和人才储备方面，与波士顿、旧金山湾区并列为全球生命科学高地。尽管近几年资本市场下滑导致行业普遍裁员，但圣地亚哥仍然是新药研发重镇。 2025年，美国 FDA 药品评价与研究中心（CDER）批准了 46 种此前从未在美国获批或上市的新药，即所谓的创新药物。尽管较2024年的 50 种和2023年的 55 种新药获批数略有下降，但仍延续了高获批数量的趋势。2025年获批的药物包括 34 种新分子实体（NME）和 12 种生物制剂，其中肿瘤（占获批药物总数的35%）和罕见病领域尤为突出。小分子药物仍然占据主导地位（67%），许多小分子药物具有全新的作用机制。主要审批趋势：肿瘤领域领先地位：精准肿瘤治疗，尤其是在非小细胞肺癌 (NSCLC) 领域，是重点关注方向。罕见病领域推进：FDA 批准了 23 种疗法（占总数的 50%）获得孤儿药资格认定，用于治疗罕见且特殊的疾病。生物制剂和先进疗法：生物制剂占获批药物的 26%，其中包括 7 种单克隆抗体 (mAb)，2 种抗体药物偶联物 (ADC)，以及 1 种双特异性抗体。 TIDES药物创新：4 种创新TIDES药物（寡核苷酸和肽）获得批准，占获批药物总数的 9%。审批速度：尽管内部人员流动以及政府停摆对各机构造成影响，FDA 仍保持了高效及时的审批速度，70% 的新药快于其他国家获批上市。 2025年美国新药审批监管分类： 21种（46%）新获批的疗法获得了优先审评资格，这是 FDA 授予那些预期疗效优于现有标准疗法的药物的监管认定。这一比例低于过去五年平均水平57%。获得优先审评资格的药物通常在提交申请后6个月内完成审评，而获得标准审评资格的药物则需要10个月。 23种（50%）新获批的药物获得了孤儿药资格认定，该资格适用于美国境内患病人数少于20万的罕见病。这些药物的申请、资助单位可获得各种激励措施，包括部分临床试验的税收抵免、免除用户费用以及潜在的市场独占权。 15种（33%）新获批的药物获得了突破性疗法资格认定，该资格适用于那些疗效优于现有疗法的药物。这些药物的申请、资助单位可获得与 FDA 更频繁的会面机会，以及在整个药物研发过程中更深入的监管指导。 11种（24%）新药获得了加速审批，其依据是替代终点指标的改善，FDA 认为这些指标“极有可能”预测临床获益。加速审批缩短了新药的整体研发周期。药企需要开展验证性试验，以提供实际临床获益的证据。 2025年美国新药列表: Drug (brand name) Sponsor Properties Indication Datopotamab deruxtecan (Datroway) Daiichi Sankyo TROP2-targeted ADC; topoisomerase inhibitor payload HR-positive, HER2-negative breast cancer Treosulfan (Grafapex) Medexus DNA alkylating drug Preparative regimen for haematopoietic stem cell transplantation for cancers Suzetrigine (Journavx) Vertex NaV1.8 inhibitor Acute pain Mirdametinib (Gomekli) SpringWorks/Merck KGaA MEK1/2 kinase inhibitor Neurofibromatosis type 1 Vimseltinib (Romvimza) Deciphera/Ono CSF1R kinase inhibitor Tenosynovial giant cell tumours Gepotidacin (Blujepa) GSK Triazaacenaphthylene bacterial type II topoisomerase inhibitor Uncomplicated urinary tract infections Fitusiran (Qfitlia) Genzyme/Sanofi Antithrombin-targeted siRNA Bleeding episodes in haemophilia A or B Atrasentan (Vanrafia) Novartis Endothelin receptor antagonist Proteinuria in adults with primary IgAN Penpulimab (Penpulimab) Akeso Biopharma PD1-targeted mAb Nasopharyngeal carcinoma Nipocalimab (Imaavy) Janssen/J&J Neonatal Fc receptor-targeted mAb Generalized myasthenia gravis Avutometinib plus defactinib (Avmapki Fakzynja Co-Pack) Verastem MEK1 inhibitor plus FAK kinase inhibitor KRAS-mutated recurrent low-grade serous ovarian cancer Telisotuzumab vedotin (Emrelis) AbbVie c-Met-targeted ADC; microtubule inhibitor payload Non-squamous NSCLC with high c-Met protein overexpression Acoltremon (Tryptyr) Alcon Labs TRPM8 thermoreceptor agonist Dry eye disease Clesrovimab (Enflonsia) Merck & Co. RSV fusion protein-targeted mAb RSV lower respiratory tract disease prevention in neonates and infants Taletrectinib (Ibtrozi) Nuvation ROS1 kinase inhibitor ROS1-positive NSCLC Garadacimab (Andembry) CSL Behring Activated factor XII-targeted mAb Hereditary angioedema prevention Linvoseltamab (Lynozyfic) Regeneron BCMA × CD3 bispecific T cell engager Multiple myeloma Sunvozertinib (Zegfrovy) Dizal Jiangsu EGFR kinase inhibitor NSCLC with EGFR exon 20 mutations Sebetralstat (Ekterly) KalVista Plasma kallikrein inhibitor Hereditary angioedema attacks Delgocitinib (Anzupgo) Leo Pharma Janus kinase inhibitor Hand eczema Sepiapterin (Sephience) PTC Phenylalanine hydroxylase activator Hyperphenylalaninemia Aceclidine (Vizz) Lenz Cholinergic agonist Presbyopia Dordaviprone (Modeyso) Chimerix/Jazz ClpP protease activator Diffuse midline glioma with H3 K27M mutations Zongertinib (Hernexeos) Boehringer Ingelheim HER2 kinase inhibitor Non-squamous NSCLC with HER2 activating mutations Brensocatib (Brinsupri) Insmed DPP1 inhibitor Non-cystic fibrosis bronchiectasis Donidalorsen (Dawnzera) Ionis Prekallikrein-targeted ASO Hereditary angioedema prevention Rilzabrutinib (Wayrilz) Genzyme/Sanofi BTK kinase inhibitor Immune thrombocytopenia Pembrolizumab plus berahyaluronidase alfa (Keytruda Qlex)a Merck & Co. PD1-targeted mAb and an endoglycosidase to enable subcutaneous delivery Solid tumours approved for the intravenous formulation of pembrolizumab Elamipretide (Forzinity) Stealth Mitochondrial cardiolipin binder Muscle strength in Barth syndrome Imlunestrant (Inluriyo) Eli Lilly Selective oestrogen receptor degrader ER-positive, EGFR2-negative, ER1-mutated breast cancer Paltusotine (Palsonify) Crinetics Somatostatin receptor agonist Acromegaly Remibrutinib (Rhapsido) Novartis BTK kinase inhibitor Spontaneous urticaria Nerandomilast (Jascayd) Boehringer Ingelheim PDE4 inhibitor Idiopathic pulmonary fibrosis Elinzanetant (Lynkuet) Bayer Healthcare NK1 and NK3 receptor antagonist Vasomotor symptoms due to menopause Doxecitine plus doxribtimine (Kygevvi) UCB Pyrimidine nucleosides Thymidine kinase 2 deficiency Ziftomenib (Komzifti) Kura Menin inhibitor AML with a susceptible NPM1 mutation Plozasiran (Redemplo) Arrowhead ApoC-III-targeted siRNA Triglycerides in familial chylomicronemia syndrome Sevabertinib (Hyrnuo) Bayer Healthcare HER2 kinase inhibitor Non-squamous NSCLC with HER2 activating mutations Sibeprenlimab (Voyxact) Otsuka APRIL-targeted mAb Proteinuria in primary IgAN Lerodalcibep (Lerochol) LIB Therapeutics PCSK9-targeted adnectin LDL-C-lowering in hypercholesterolaemia Etripamil (Cardamyst) Milestone Calcium channel blocker Paroxysmal supraventricular tachycardia Zoliflodacin (Nuzolvence) Entasis/Innoviva Spiropyrimidinetrione bacterial type II topoisomerase inhibitor Urogenital gonorrhea due to Neisseria gonorrhoeae Depemokimab (Exdensur) GSK IL-5-targeted mAb Severe asthma, eosinophilic phenotype Aficamten (Myqorzo) Cytokinetics Cardiac myosin inhibitor Obstructive hypertrophic cardiomyopathy Narsoplimab (Yartemlea) Omeros MASP2-directed mAb Haematopoietic stem cell transplant-associated thrombotic microangiopathy Tradipitant (Nereus) Vanda NK1 receptor antagonist Vomiting induced by motion 主要参考资料： 1) Nature Reviews Drug Discovery 25, 163 (2026) 2) Nature Reviews Drug Discovery 25, 81-87 (2026) 3) fda.gov/drugs/novel-drug-approvals-fda/novel-drug-approvals-2025 4) AACR.org

100 项与 D-3263 相关的药物交易

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适应症	最高研发状态	国家/地区	公司	日期
晚期恶性实体瘤	临床1期	美国	Dendreon Corp.	2009-03-01
前列腺增生症	临床1期	-	Dendreon Corp.	-

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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


ARVO2023	临床3期	干眼综合征	-	AR-15512	衊遞獵憲獵廠糧淵衊蓋(觸齋顧鏇積選壓網鏇獵) = 壓選範廠淵襯鬱襯醖醖構醖齋糧顧糧襯繭淵夢 (膚蓋構鏇膚糧鑰獵選願 )	-	2023-04-23
				icilin	衊遞獵憲獵廠糧淵衊蓋(觸齋顧鏇積選壓網鏇獵) = 選遞艱鹽鑰觸窪選鏇觸構醖齋糧顧糧襯繭淵夢 (膚蓋構鏇膚糧鑰獵選願 )