Our preclinical study confirmed that copper accumulation can lead to radioresistance in vitro and in vivo, and reducing the concentration of copper with copper chelator help to overcome radioresistance. Therefore, the investigators plan to carry out a prospective interventional phase II clinical trial to explore the safety and efficacy of penicillamine (a common copper chelator) as a radiosensitizer in the treatment of recurrent head and neck cancer.

开始日期2023-11-15

申办/合作机构

南方医科大学南方医院

IRCT20200407046981N49

/ SuspendedN/AIIT

Comparative bioequivalence study of the Penicillamine 250-mg Capsules manufactured by Vana Darou Gostar Company with Penicillamine brand capsules (Cupripen®) by Laboratorios Rubio company

开始日期2022-12-11

申办/合作机构-

NCT03957720

/ Recruiting早期临床1期IIT

The Individual Therapy for Patients With Wilson's Disease

Based on the genotype characteristics and genotype-phenotype-treatment prognosis data of Chinese WD patients, this study intends to further optimize the treatment regimen of Chinese WD patients and formulate individualized treatment regimens for each genotype, so as to further improve the prognosis of patients.

开始日期2019-03-15

申办/合作机构

浙江大学医学院附属第二医院（浙江省第二医院）

100 项与青霉胺相关的临床结果

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100 项与青霉胺相关的转化医学

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100 项与青霉胺相关的专利（医药）

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8,618

项与青霉胺相关的文献（医药）

2025-11-01·Neural Regeneration Research

Copper homeostasis and neurodegenerative diseases

Article

作者: Wang, Guoqing ; Zhang, Feng ; Li, Daidi ; Wang, Yuanyuan ; Xu, Kaifei

Copper, one of the most prolific transition metals in the body, is required for normal brain physiological activity and allows various functions to work normally through its range of concentrations. Copper homeostasis is meticulously maintained through a complex network of copper-dependent proteins, including copper transporters (CTR1 and CTR2), the two copper ion transporters the Cu -transporting ATPase 1 (ATP7A) and Cu-transporting beta (ATP7B), and the three copper chaperones ATOX1, CCS, and COX17. Disruptions in copper homeostasis can lead to either the deficiency or accumulation of copper in brain tissue. Emerging evidence suggests that abnormal copper metabolism or copper binding to various proteins, including ceruloplasmin and metallothionein, is involved in the pathogenesis of neurodegenerative disorders. However, the exact mechanisms underlying these processes are not known. Copper is a potent oxidant that increases reactive oxygen species production and promotes oxidative stress. Elevated reactive oxygen species levels may further compromise mitochondrial integrity and cause mitochondrial dysfunction. Reactive oxygen species serve as key signaling molecules in copper-induced neuroinflammation, with elevated levels activating several critical inflammatory pathways. Additionally, copper can bind aberrantly to several neuronal proteins, including alpha-synuclein, tau, superoxide dismutase 1, and huntingtin, thereby inducing neurotoxicity and ultimately cell death. This study focuses on the latest literature evaluating the role of copper in neurodegenerative diseases, with a particular focus on copper-containing metalloenzymes and copper-binding proteins in the regulation of copper homeostasis and their involvement in neurodegenerative disease pathogenesis. By synthesizing the current findings on the functions of copper in oxidative stress, neuroinflammation, mitochondrial dysfunction, and protein misfolding, we aim to elucidate the mechanisms by which copper contributes to a wide range of hereditary and neuronal disorders, such as Wilson’s disease, Menkes’ disease, Alzheimer’s disease, Parkinson’s disease, amyotrophic lateral sclerosis, Huntington’s disease, and multiple sclerosis. Potential clinically significant therapeutic targets, including superoxide dismutase 1, D-penicillamine, and 5,7-dichloro-2-[(dimethylamino)methyl]-8-hydroxyquinoline, along with their associated therapeutic agents, are further discussed. Ultimately, we collate evidence that copper homeostasis may function in the underlying etiology of several neurodegenerative diseases and offer novel insights into the potential prevention and treatment of these diseases based on copper homeostasis.

2025-08-01·JOURNAL OF AFFECTIVE DISORDERS

Epidemiology and effect of psychiatric comorbidities on survival rates in patients with systemic sclerosis: A nationwide population-based cohort study

Article

作者: Chang, Yu-Sheng ; Lee, Yao-Tung ; Wu, Fang-Yi

BACKGROUND:

Systemic sclerosis (SSc) is a chronic, disabling connective tissue disease with a considerable psychological burden. While studies suggest a higher prevalence of psychiatric disorders in SSc, most have small sample sizes.

METHODS:

Using Taiwan's National Health Insurance Research Database, we identified 3270 SSc patients from the catastrophic illness registry and matched them 1:4 by age and sex with 13,080 controls. We compared the incidence rate ratios (IRRs) of new psychiatric disorder diagnoses between the two groups and analyzed risk factors using a Cox proportional hazards model. Kaplan-Meier analysis and log-rank test were used to compare survival in SSc patients with and without psychiatric conditions (matched at a 1:4 ratio by age, sex and CCI). We compared psychiatric disorder incidence rates.

RESULTS:

The SSc group had a significantly higher incidence of psychiatric disorders than controls (IRR = 1.66, p < 0.001). In SSc patients, treatment with an oral daily steroid dose of ≥7.5 mg (hazard ratio [HR] = 1.71, p = 0.010), intravenous steroid pulse therapy (HR = 2.34, p < 0.0042), or D-penicillamine (HR = 1.60, p < 0.001) served as an independent risk factor for psychiatric comorbidities. SSc patients with psychiatric comorbidities had significantly lower survival rates than those without.

CONCLUSIONS:

Patients with SSc are at an increased risk of psychiatric comorbidities, which can negatively affect their survival rates. Treatment with a daily oral steroid dose of ≥7.5 mg, intravenous steroid pulse therapy, or D-penicillamine is a risk factor for psychiatric comorbidities in SSc.

2025-06-01·AQUATIC TOXICOLOGY

Evaluating cell surface extraction methods for improved assessment of silver nanoparticle bioaccumulation

Article

作者: Kantarciyan, Arin ; Segovia-Campos, Inés ; Slaveykova, Vera I

Methods to differentiate surface-bound and internalized Ag in phytoplankton are essential for understanding bioaccumulation but remain limited, especially for studies involving silver nanoparticles (AgNPs). To address this, we assessed biologically relevant ligands for extracting adsorbed Ag from Chlamydomonas reinhardtii and Cyclotella meneghiniana exposed to Ag⁺ or AgNPs, focusing on ligand type, concentration, and extraction time. Additionally, we examined the impact of these agents on AgNP stability and microalgal membrane integrity. The ligands l-histidine, l-glutamine, l-cysteine, and d-penicillamine were tested. The thiol-containing d-penicillamine, tested for the first time, showed the highest efficiency in desorbing Ag⁺ from Ag⁺-treated cells, followed by l-cysteine. Optimal conditions were 1 mmol L⁻¹ ligand concentration and 5 min contact time. For AgNP-exposed cells, two sequential cell resuspensions in Ag-free medium were sufficient to detach loosely bound AgNPs. Then, hydrogen peroxide (H₂O₂), a biologically relevant oxidant, was introduced for the first time in the extraction procedure to facilitate the oxidative dissolution of nanoparticles. A combination of 0.5 mmol L^-1 H₂O₂ with a 1 mmol L^-1l-cysteine or d-penicillamine effectively removed Ag from the cell walls of C. meneghiniana and C. reinhardtii. The tested extraction agents did not affect unexposed phytoplankton cells. However, AgNP-exposed cells treated with H₂O₂ showed slightly increased cell membrane damage in diatoms. A dissolution of AgNP was found in the presence of l-histidine and d-penicillamine and H₂O₂. These findings highlight the need to develop species-specific washing methodologies in AgNPs bioaccumulation studies and provide insight into optimized extraction methods for assessing AgNP adsorption, internalization, and toxicity.

项与青霉胺相关的新闻（医药）

2025-05-08

·云南白药

【云南日报报道】织密健康保障网守护群众生命线——省医药公司创新医药品配送保障健康云南

作为云南白药集团的全资子公司，云南省医药有限公司（以下简称“省医药公司”）始终以守护人民健康为使命，深耕医药流通与创新服务领域，逐步成长为全省医药流通与创新服务的“领军者”，打造了一站式采购解决方案、全渠道配送、数字化商务协同、医药品牌运营等服务体系。2023年，省医药公司在全国医药流通百强企业中排名第12位。2024年，公司营业收入突破246.07亿元，承担全省超50%的医药物资配送任务，为全省医疗体系的高效运转提供了坚实保障。1998年以来，省医药公司始终是云南应急医疗物资的“压舱石”之一，承担着省级医药储备责任。目前，储备资金规模达4200万元，覆盖灾情疫情急救、政府战略储备等关键领域，确保关键时刻“调得出、用得上”。以患者需求为核心，目前省医药公司已按病种搭建患者全生命周期（全病程）健康管理服务体系，在保障日常用药的同时，通过积极引入新药、推动援助药活动开展、保障生命急救所需药物，以及配送腹膜透析液进城乡患者家门等服务，数十年如一日，不计成本、不遗余力地帮助患者更加便捷地获取到可靠的药物。布局新特药房满足多元化健康需求“请问你们这里有青霉胺片吗？”2024年7月末，一个德宏州建档立卡户向省医药·新特药房提出需求。青霉胺片属特殊用途药品，日常用量较少，通常难以买到。接到需求后，省医药公司立即启动应急采购机制，直联药品供应商完成供应链对接，短时间内，就将药品直接配送到患者手中，彰显了医疗保障体系对贫困群体的精准响应效率。从供应链服务商到健康生态构建者，这样的案例在省医药公司不胜枚举，作为扎根云南70多年的医药流通企业，目前，在全省14个州市，省医药·新特药房已经有28家零售门店，大部分都毗邻核心三级标杆医院。省医药公司始终坚持守护云岭百姓健康的“共同体”信念，服务5500多家供应商，经营110000多个品规数，并提供全方位、全类别的药品药事服务，包括急抢救药类、短缺药、罕见病用药、全球创新药，全力保证将这些药品送达患者。“云找药”小程序打通便民服务“最后一公里”点开“云找药”小程序，搜索所需药品，距家最近的省医药·新特药房成功锁定库存——这正是“云找药”上线以来为近10万患者搭建的购药绿色通道日常写照。平台价格透明、搜索药品实时比价，处方药支持线上互联网医院在线复诊开方，节省到院排队时间，下单后可选择快递邮寄到家、线下实体店到店自取、门店周边冷链配送上门等多种取药方式，让患者的购药过程更加灵活便捷。过去，罕见病患者面临找药渠道不顺畅、药品可及性差、药房库存信息掌握不清等问题。“云找药”聚焦罕见病患者“寻药难题”，罕见病人亟待用药的时候，“云找药”可以直联供应商，整合国内外药企资源，提供24小时内精准找药反馈服务。为解决偏远地区“购药远、配送难”问题，“云找药”让山区老人、留守家庭不再因一盒药辗转奔波，足不出户就能购买所需药品。强化冷链物流管理守护药品质量生命线在省医药·新特药房大观零售店，一名患者提出需求：紧急需要艾加莫德注射液。艾加莫德注射液属罕见病用药且为冷链药品，对运输、存储要求极高。时间紧、任务重，店长与质量负责人紧急制定方案，最终由健康管理员担起重任，携带保温箱全程确保药品温度进行配送。仅经过五个小时的车程，店员便抵达文山，将药品保质保量地送到患者手中。“每个药都承载着生命的希望，每一次配送都关系到患者的健康。我们坚持以患者为中心，不计成本用最高效的配送方案，用速度传递希望。”省医药公司相关负责人如是说。在物流中心，标准化、专业化和数字化的管理，让省医药公司实现了产品从收货验收到配送交付的闭环管理，流通效率不断提高。目前，省医药公司每天出货量达2万件以上，最高峰曾承载12万件的出货量。面对患者急需用药的需求，省医药公司始终坚持通过线路网络优化、多式联运、干支线运输等方式，推出当日达、次日达、隔日达、约定达等一系列服务产品，缩短交货时间，并以动态看板的形式复盘配送线路时效、合理性，满足配送时效的前提下有效控制成本，综合运用高铁、飞机等社会资源，满足急抢救药品的配送需求，同时结合省内油价梯度定价政策，确定合理的加油站点，有效控费。为了确保生物制剂、血液制品、诊断试剂等冷链商品的质量与安全，省医药公司在商品的入库、存储及配送全链条中，依托完善的冷链管理系统，严格遵循温控标准（2—8℃或其他更为严格的温区），全方位保障商品的品质与有效性，为患者和医疗机构提供可靠的保障。省医药公司的冷库面积达2000多平方米，可满足15000件商品的在库储存。在冷库综合作业区设置的作业缓冲区及气囊门，支持冷库与冷藏车无缝对接，实现在冷链环境中收货及装车。在管理过程中，为了科学、及时、有效地关注药品的质量情况，所有的冷库、冷藏车和保温箱均配备了独立的温湿度监测系统；冷链产品到货时，从冷库收货区检查到货运输方式及运输过程的温度记录、运输时间，测量到货温度；冷链产品交付时，通过车载蓝牙打印机将过程温度记录打印给客户，实现了冷链全过程无断链，温度数据可追溯的冷链闭环管理。科技赋能全方位建立运营体系随着我国医疗卫生事业的发展，医疗科学技术的不断进步以及材料科研水平的不断提高，医用耗材在临床医学中的使用量越来越大，已然成为医疗活动中的重要组成部分，加强成本管控、提升运营管理水平，成为目前医院的现实需求。在过去的传统管理模式中，医用耗材的管理涉及采购、库房、科室多个部门，存在管理分散、缺乏统一协调、各部门间、数据不互通，医院难以全局掌握耗材使用情况等问题。在这样的背景下，省医药公司以客户为中心，结合医院实际需求，为客户量身打造定制化的医用耗材院内精细化管理解决方案，旨在协助客户进一步提升医用耗材在院外采供协同与院内流转消耗的规范化、精细化管理，降低管理难度和管理成本。相较于传统管理模式，SPD管理模式借助物联网、RIFD技术、智能柜以及信息系统等科技赋能下的精细化管理，简化了医院端的管理环节，让医院实现从分散到全流程整合的管理模式，从医院全自主管理到重点环节监管，从人工到信息化、从经验驱动到数据驱动的库存管理、从被动到全生命周期监管，帮助医院等医疗机构聚焦临床服务和重点环节服务质量监管，在降低成本的同时，不断提升质效。从数字化运营平台到数字化物流平台，再到数字化客户服务平台，省医药公司已建立全链条运营保障体系。一直以来，省医药公司始终承担着供应商与医院之间的沟通桥梁角色，致力于实现药品信息的及时共享与高效传递，全力保障患者用药可及性。转发自：云南日报往期阅读推荐·政企联动深化产才融合，“白药之家”正式揭牌启用·云南白药集团医疗器械事业部闪耀湖北省医学会康复学术会议·云药与云花共生一起健康“楹”新高·阳光正好，清爽出游！「云找药」陪您来赏蓝花楹！·花儿为什么这样红：云南这座古城就是这么City，这个产业就是这么Fly·青力量白药魂 | 百年匠心传薪火五四热血铸芳华·「健康花事」从街头漫进生活的褶皱里

带量采购高管变更财报核酸药物

2025-05-02

·医药速览

环肽发现：美国麻省理工报道一种基于亲和-质谱（AS-MS）筛选的大环肽发现方法，可达亿级通量

Early R&D Talking聚焦环肽DOI: 10.1126/sciadv.adr1018侃侃而言学以致用相比于小分子和大分子生物制剂，环肽在稳定性、细胞通透性、结合亲和力、以及口服生物利用度等方法具有综合性的优势，尤其适合靶向蛋白质-蛋白质相互作用（PPI）；然而，用于大环肽配体发现和开发的大型文库在一定程度上备受限制：要么通量高、但化学空间有限（如展示环肽文库，通常>108）；要么化学多样性高、但规模通量有限（如合成环肽文库，通常<108）。近期（Mar. 19），美国麻省理工学院（MIT）在Science Advances上报道了一种通过亲和-质谱（AS-MS）筛选的方法，可从包含天然和非天然氨基酸的成亿规模的大环肽文库中，发现具有潜力的蛋白质靶标环肽配体。这种高通量的方法：① 首先，采用 “拆分-合并” 的组合方法，利用 I2 溶液氧化 Cys 及其类似物残基，高效、定量环化构建二硫键大环肽；② 随后，通过亲和力筛选，分离靶标高亲和力配体；③ 进而，利用 DTT (二硫苏糖醇）处理使大环肽定量线性化还原；④ 再之后，利用标准串联质谱鉴定、并发现线性肽类似物。利用这种方法，研究人员完成了对两个靶标（Cadherin-2、抗血凝素抗体克隆12ca5）的 POC 验证，发现了高效（nM级亲和力）大环肽结合物。这种方法将促进大环肽文库在治疗肽开发中的应用。本篇研究更是提出了一种 AS-MS + “冷点优化” 的打破常规的优化策略，值得借鉴。原文开源，文末点击“阅读原文”可直达原文地址。01环肽的优势、挑战与创新 1.1 环肽的优势相比于小分子，大环肽具有破坏蛋白质-蛋白质相互作用（PPI）的优势；相比于生物大分子，大环肽具有跨越生物膜的优势；相比于线性前体，环化后的大环肽具有几个潜在的优势，如：加强的蛋白质水解稳定性、细胞渗透性、结合亲和力、和口服生物利用度。蛋白酶通常会与呈β-折叠构象的肽结合并将其降解，而环化则可通过限制肽主链对酶活性位点的构象可及性来提供抗蛋白水解性，并且环化还可获得特定的可设计支架（如钉接 α-螺旋）。对于细胞通透性设计，一般从分子量、极性表面积、氢键相互作用以及化合物的形状等策略调节。除此之外，目前实现被动细胞通透性的设计原则的核心是大环化。结合蛋白水解稳定性和被动渗透性，可以赋予基于肽的候选药物口服生物利用度，一般也可以通过药物配方来进一步提高。因此，大环肽文库更适合与基于亲和筛选的肽配体发现平台联用。此外，基于大环肽文库筛选直接鉴定发现的大环肽配体结合物可以减轻优化合适环化位点的需要，从而简化后续开发工作。而且，大环化带来的构象约束可以提高文库中针对挑战性靶标的配体发现率。 1.2 现有大环肽制备和发现的瓶颈基于遗传编码发现平台通常访问大环肽文库，重点关注高多样性（>108），而合成文库可以访问低多样性（<108）的非天然化学空间。更稳定的大环化方式是环肽文库的首选，然而，基于二硫键的大环肽更适合用于配体发现阶段，不需要任何化学修饰或处理，同时，也不影响一些基于基因扩增平台的数据处理。二硫键在基于噬菌体展示发现平台中用于大环肽文库的构建已经应用了超过二十年，并在临床获批的药物中也经常见到，如奥曲肽、降钙素等。此外，二硫键也经常在后续的优化中被替代，许多可替代的策略包括硫醚键、酰胺键、碳桥、二烯键、或三唑桥等。 1.3 创新性方法在合成文库中使用二硫大环化是一种高效且易于实现的方法，并且不需要额外的纯化步骤。由于其不能进行基因编码和扩增，因此，合成文库常用于直接筛选，通过亲和力筛选，结合质谱进行解码解析。因此，本文提出一种创新的方法：环化与线性化还原技术相结合，进行基于亲和力的质谱筛选（AS-MS）发现大环肽。在质谱（MS）中解码大环肽序列是非常复杂的，这也是合成大环肽文库在亲和力筛选发现平台中的历史性限制。用来解码大环肽的试验方法包括：质谱的计算处理、和化学触发线性化还原。环化：通过碘水快速氧化（＜15 min）构建 Cys 及其类似物的二硫键环化。验证方法：通过 Ellman 试验和大小排斥色谱（SED）验证文库的完整性，以确认合成文库的近定量分子内大环化。线性化还原：通过加热和1,3-二硫苏糖醇（DTT）轻度还原来使二硫键还原线性化，并通过 Ellman 的分析来确认，以实现标准串联质谱（MS/MS）测序。整个基于AS-MS 的大环肽配体发现流程如下图所示：02POC 验证与结论 2.1 亿计规模大环肽文库设计与构建如下图，研究人员设计了两种类型的文库：CX12CK、X6CX6CK。其中 X 代表除半胱氨酸（Cys）和异亮氨酸（Ile）以外的 18 种典型天然氨基酸，（排除 Cys 是为了控制二硫键的形成，排除 Ile 是因为它与 Leu 分子质量相同）。C 为 Cys 及其类似物（高半胱氨酸、青霉胺）。研究人员采用 20 μm 树脂（8.33 g树脂，共2.00 mmol），采用 “拆分-合并” 固相合成方法合成大环肽文库。如下图 A，采用 Ellman 测试法定量测定硫醇氧化，检测在 280 nm吸收光下的归一化吸收，可以看出碘促进高效环化。合成的文库硫醇换了经裂解、冷醚研磨、SPE、去除剩余的还原剂后，采用 Ellman 试剂测定完整性。如下图所示，与标准肽相比，只观察到单体文库物种，表明形成的二硫键是分子内而不是分子间的。从数据中也可以看出，与CX12CK文库设计相比，X6CX6CK 文库设计总体上具有更高的置信度，这表明在序列分配中片段事件期间中间Cys 位置的优势。总的说来，这些结果说明大环肽文库的 “拆分-合并” 合成、氧化环化、还原线性化和串联质谱测序解码是成功的。 2.2 抗血凝素抗体12ca5的配体发现首先，研究人员以 12ca5 作为模型蛋白靶标，进行AS-MS 的大环肽文库的 POC 筛选验证。以已知的靶标结合序列 D**DY（A/S）肽段序列作为 AS-MS 文库筛选的基准。筛选结果表明，从 X6CX6CK 设计文库中拉下 7 个高亲和肽配体，而从 CX12CK 设计文库中仅拉下 1 个肽配体。使用生物层干涉法（BLI）合成并验证了这些序列的结合亲和力。所有鉴定的结合物在低 nM到高 pM 范围内表现除明显的解离常数（Kd），接近仪器检测的下限，如上图。结合基序在 X6CX6CK 文库中发现的所有序列中都存在于相同的位置或移码。尤其是库设计中间的Cys 类似物位于 12ca5 基序的第三个位置，即D*ΨDY(A/S），其中Ψ是Cys，同型Cys或青霉胺。 2.3 CDH2结合肽的发现与优化针对 CDH2 ，利用AS-MS，从两个文库中均发现了 nM 级肽配体。其中一种具有高测序置信度的肽被鉴定为针对 CDH2 富集，即下图中CBP。通过 BLI 合成并测试了 CBP 与 CDH2 的结合亲和力，Kd= 53 nM。此外，研究人员也合成了 CBP 对应的线性肽结构，其Kd = 150 nM。对比表明，大环化的 CBP 的刚性结构更有利于获得高亲和力。随后，研究人员针对 CBP进行了单残基替代研究，以进行SAR 探究，包括丙氨酸扫描和D-氨基酸扫描、截断片段研究。Cys7-Pen14 二硫键在所有的SAR探究中被保留，以提供一个一致的大环结构进行优化。首先，通过合成具有单个丙氨酸突变的13个变体进行丙氨酸扫描，并用 BLI 对 CDH2进行检测。结果表明，多个残基对Hotspot 结合很重要，包括Lys4、Phe6、Lys12、Lys15，当替代它们时，肽与靶标的结合完全消融。其它残基，如Met2、Thr3、Leu5、Thr10、Tyr11、和Asp13 对结合没有影响（Coldspots）。其次，截断研究侧重于从N端缩短CBP，产生5个额外的肽用于 BLI 测试。结果验证了N 端残基对结合亲和力的重要影响，尤其是Phe6、Leu5，而Met2、Thr3对靶标结合贡献最小。下一个第三，通过D-氨基酸扫描，确定了立体化学对配体相互作用的影响。结果发现Phe6、Tyr11的立体重要性，也进一步强化了芳香残基对结合的重要性。综上所述，这些初步的 SAR 研究概述了似乎驱动 CBP 与 CDH2 高亲和力结合的热点残基，包括Lys4、Phe6、Lys12和Lys15，而Met2、Thr3、Leu5、Thr10和Asp13被指定为对结合影响最小的冷点。SAR 数据为基于 CBP 的两个集中性文库的设计提供了信息：一个衍生出高亲和力的热点残基，另一个衍生出非结合必需的冷点残基。此前设计非典型文库的方法是使热点多样化，然而，肽的开发和优化往往也会考虑到冷点残基不驱动高亲和力结合的靶标。这些冷点残基对于改善结合亲和力、溶解度或蛋白水解稳定性具有非直观的关键作用。因此，研究人员选择比较两种成熟策略的结果。如下图，根据对接、丙氨酸扫描、D-氨基酸扫描、姐u但研究提供的数据，选择纳入热点和冷点的集中型文库对的非典型氨基酸集。通过设计冷点替代为非天然氨基酸，优化冷点集中型文库，进而筛选出了新的肽段，NCBP-4，其结合解离常数 Kd= 29 nM，结合响应提升了 2 倍，蛋白酶半衰期更是延长了 40 倍（5分钟→200分钟）。03总结与展望这篇研究通过碘氧化法实现大规模（亿计）环肽文库的构建和筛选，结合 AS-MS 高效发现高亲和力环肽配体，并通过两个POC 证明了方法的可行性。同时，文中通过打破常规，采用冷点优化的策略，替代非天然氨基酸显著提高了肽配体的结合亲和力和稳定性，为环肽优化提供了新的思路。AS-MS + “冷点优化”，加速环肽配体的优化，减少后续开发中的稳定性问题，为环肽药物开发提供了一种高效的新策略。推文用于传递知识，如因版权等有疑问，请于本文刊发30日内联系医药速览。原创内容未经授权，禁止转载至其他平台。有问题可发邮件至yong_wang@pku.edu.cn获取更多信息。©2021 医药速览保留所有权利往期链接“小小疫苗”养成记 | 医药公司管线盘点人人学懂免疫学| 人人学懂免疫学（语音版）综述文章解读 | 文献略读 | 医学科普|医药前沿笔记PROTAC技术| 抗体药物| 抗体药物偶联-ADC核酸疫苗 | CAR技术| 化学生物学温馨提示医药速览公众号目前已经有近12个交流群（好学，有趣且奔波于医药圈人才聚集于此）。进群加作者微信（yiyaoxueshu666）或者扫描公众号二维码添加作者，备注“姓名/昵称-企业/高校-具体研究领域/专业”，此群仅为科研交流群，非诚勿扰。简单操作即可星标⭐️医药速览，第一时间收到我们的推送①点击标题下方“医药速览” ②至右上角“...” ③点击“设为星标

抗体药物偶联物

2025-04-28

·Pharmaceutical Technology

Innorna secures dual FDA designations for Wilson’s disease mRNA therapy

IN013 restores functional protein levels to reduce systemic copper build-up in patients with Wilson’s disease. Image credit: Shutterstock / Kateryna Kon. The US Food and Drug Administration (FDA) has granted rare paediatric disease and orphan drug designations for IN013, Innorna’s mRNA therapeutic for Wilson’s disease. China-headquartered Innorna will now be in line for tax credits for US-based clinical trials. If IN013 is approved, the potential for seven years of market exclusivity in the designated indication, in accordance with orphan drug status benefits. The rare paediatric disease designation, meanwhile, given to biotechs developing treatments for diseases that affect fewer than 200,000 US paediatric patients, could mean Innorna receives a priority review voucher (PRV) if the therapy is approved. This voucher would allow the company to fast-track a future candidate of its choice through FDA review, meaning it will reach the market four months sooner if approved. Innorna could also sell the voucher for a quicker cash injection – vouchers have typically been sold for around $100m over the past few years. Wilson’s disease is a rare inherited disease that causes copper levels to build up in the body’s organs, including the liver and brain. The disease is caused by mutations in the ATP7B gene, which normally encodes for the protein responsible for eliminating excess copper. Symptoms of the illness include hepatic and neurological damage, ocular abnormalities, and kidney injury, among others. It is estimated that one in every 30,000 individuals is affected by the disease, with isolated populations at higher risk due to consanguineous marriages. The current standard of care is the administration of copper chelating agents – compounds that bind to copper ions to reduce toxicity and facilitate the removal. In 2022, the FDA greenlit the first new treatment for Wilson’s disease in 30 years, Orphalan’s Cuvrior (trientine tetrahydrochloride). Comprising a copper chelating agent, Cuvrior is for patients who are de-coppered and able to take D-penicillamine, another drug approved for the disease. GlobalData Strategic Intelligence US Tariffs are shifting - will you react or anticipate? Don’t let policy changes catch you off guard. Stay proactive with real-time data and expert analysis. By GlobalData Learn more about Strategic Intelligence Innorna states that current treatments offer limited efficacy and carry risks, such as hepatorenal toxicity or exacerbated neurological symptoms. Some Wilson’s disease patients taking penicillamine have experienced nervous system deterioration . Unlike current approaches that regulate copper levels downstream, Innorna’s IN013 enables the production of the ATP7B protein. The biotech states its asset, developed on an mRNA lipid nanoparticle platform, can restore functional protein levels to reduce systemic copper build-up. Other companies are also developing new treatments for Wilson’s disease. Vivet Therapeutics and Pfizer are developing a gene therapy called VTX-801, currently in a Phase I/II trial (NCT04537377). The candidate acts by inserting a fully functional version of ATP7B into the body. The FDA designations for Innorna come at a time of regulatory spotlight on rare disease pipelines, amid agency job cuts by US President Donald Trump and programme expirations. The PRV programme for paediatric rare diseases, for example, entered its ‘sunsetting’ phase in December 2024 after US Congress failed to reauthorise it. Experts have said the programme’s expiration, along with reduced FDA capacity, could slow down rare disease development. mRNA vaccine coverage on Pharmaceutical Technology is supported by Trilink . Editorial content is independently produced and follows the highest standards of journalistic integrity. Topic sponsors are not involved in the creation of editorial content. Free Whitepaper Enhancing Potency, Stability, and Efficiency in mRNA Read this technical note to explore the frontiers of mRNA capping in advanced therapeutic development. As mRNA-based treatments evolve, optimizing capping strategies becomes critical for enhancing stability, translation efficiency, and potency. This comparative analysis of TriLink’s CleanCap® technologies versus traditional enzymatic capping reveals the key innovations setting new benchmarks. Discover how co-transcriptional methods, structural modifications, and dose-sparing potential are accelerating the path from synthesis to impactful protein expression in both research and therapeutic settings. Thank you. You will receive an email shortly. Please check your inbox to download the Whitepaper. By Trilink Thematic By downloading this Whitepaper, you acknowledge that GlobalData may share your information with Trilink Thematic and that your personal data will be used as described in their Privacy Policy

疫苗上市批准孤儿药信使RNA临床研究

100 项与青霉胺相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
D00496	青霉胺	M01CC01	DB00859

研发状态

10 条最早获批的记录,

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适应症	国家/地区	公司	日期
重金属中毒	中国	四川制药股份有限公司	1981-01-01
铅中毒	中国	四川制药股份有限公司	1981-01-01
胱氨酸尿症	美国	Bausch Health Cos., Inc.	1970-12-04
肝豆状核变性	美国	Bausch Health Cos., Inc.	1970-12-04
类风湿关节炎	美国	Bausch Health Cos., Inc.	1970-12-04

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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


ASN2020	N/A	肝豆状核变性 antimyeloperoxidase(MPO)-ANCA \| antinuclear factors \| anti- proteinase(PR3) antibody ... 更多	-	D-Penicillamine	簾鹽窪艱遞鏇築憲簾鏇(積選膚繭壓衊顧範製鏇) = Oral zinc acetate was once truncated due to gastroenterological side effect 鹹範鹹遞壓膚鹽膚夢窪 (壓糧蓋淵鑰艱衊醖獵簾 )	-	2020-10-19
				Methyl-prednisolone
MDS2020	N/A	-	-	D-penicillamine	顧選淵製觸網簾製鹹窪(蓋顧繭鑰窪醖鑰選觸齋) = 鹹獵鹹積簾膚膚構顧憲夢憲艱膚獵簾願製願獵 (積鏇淵齋鏇憲繭範襯鹹 ) 更多	不佳	2020-09-12
ACR2015	N/A	-	-	Non-biologic DMARDs	齋膚積壓窪淵積鑰積觸(壓網獵襯構壓夢夢鹹獵) = 壓簾鏇鏇鹹獵範範網淵窪製鹽窪憲積齋獵憲鏇 (鹽壓襯簾鹹餘網獵網鹽, 13.4) 更多	-	2015-11-10
				Biologic DMARDs	齋膚積壓窪淵積鑰積觸(壓網獵襯構壓夢夢鹹獵) = 醖醖鑰膚構構糧願簾壓窪製鹽窪憲積齋獵憲鏇 (鹽壓襯簾鹹餘網獵網鹽, 7.4) 更多
EAN2015	N/A	肝豆状核变性	33	d-penicillamine (Compliant patients)	遞獵蓋憲餘鑰鬱鬱構憲(簾繭鹽顧淵壓淵簾淵衊) = 衊網鹽膚簾醖餘淵襯鹹選艱憲艱願鹹獵鹽衊構 (淵糧窪鏇廠窪製繭衊獵 )	积极	2015-06-29
				d-penicillamine (Non-compliant patients)	遞獵蓋憲餘鑰鬱鬱構憲(簾繭鹽顧淵壓淵簾淵衊) = 鬱選壓壓鬱膚選淵願醖選艱憲艱願鹹獵鹽衊構 (淵糧窪鏇廠窪製繭衊獵 )
EULAR2014	N/A	嗜酸性筋膜炎	16	D-Penicillamine plus Corticosteroids	網膚衊醖願憲廠壓鏇鹽(簾簾製淵壓窪願獵製遞) = proteinuria was unexpectedly common in both groups although it was more frequent in the D-Pen plus CS group 膚窪糧壓憲鬱膚衊窪繭 (築鹹鹹蓋願選築鹽淵製 ) 更多	-	2014-06-11
				Corticosteroids alone
ASN2011	N/A	毒性 \| 肾囊肿	-	D-Penicillamine	壓糧構蓋糧蓋壓繭鏇遞(廠選願糧廠鬱壓積觸淵) = including loosening of the skin, keratoconus, popliteal aneurysms, cutix laxa, cardiomyopathy, restrictive lung disease, thickening of the walls of the esophagus and duodenum 構夢簾醖襯鹹餘蓋願鏇 (願願鏇築鹹齋膚淵積壓 ) 更多	-	2011-11-08