Chronic itch affects approximately a fifth of the global population and is associated with substantial negative consequences for the affected individuals. Furthermore, there is a lack of efficient treat-ment options for chronic itch. Topical ketamine cream has been used successfully to relieve various forms of pain, and we hypothesize that topical ketamine relieves itch through a mechanism of action comparable to that in pain relief.
The aim of this project is to evaluate the effects of ketamine both alone and in combination with amitriptyline on histaminergic and non-histaminergic itch induced by histamine and cowhage, respectively.

开始日期2024-08-20

申办/合作机构

University of Aalborg

CTRI/2009/091/000688

/ Completed临床3期

A comparative single blind, Parallel group, non-crossover, multi-centric clinical trial of Amitriptyline 4% + Ketamine 2 % Cream in patients having Neuralgia due to diabetes, chemotherapy or shingles.

开始日期2009-10-15

申办/合作机构

Ajanta Pharma Ltd.

NCT00471445

/ Completed临床3期IIT

Assessment of Topical Treatment Response With Amitriptyline and Ketamine: Combination Trial in Chemotherapy Peripheral Neuropathy (ATTRACT-CPN)

RATIONALE: Topical cream containing amitriptyline and ketamine may help relieve pain, numbness, tingling, and other symptoms of peripheral neuropathy. It is not yet known whether topical amitriptyline and ketamine cream is more effective than a placebo in treating peripheral neuropathy caused by chemotherapy.
PURPOSE: This randomized phase III trial is studying the side effects and how well topical amitriptyline and ketamine cream work compared with a placebo in treating peripheral neuropathy caused by chemotherapy in patients with cancer.

开始日期2007-10-01

申办/合作机构

National Cancer Institute

100 项与阿米替林/氯胺酮相关的临床结果

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100 项与阿米替林/氯胺酮相关的转化医学

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100 项与阿米替林/氯胺酮相关的专利（医药）

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项与阿米替林/氯胺酮相关的文献（医药）

2026-01-01·Chemistry-An Asian Journal

A Robust Ensemble Machine Learning Approach for Inhibitor Discovery: Case Study of HIV‐1 NNRTI and Validation Using MD Simulation

Article

作者: Pani, Pratyush ; Rana, Malay Kumar ; Shree, Anvesha

Abstract:

The growing demand for new therapeutics highlights the need for intelligent, cost‐effective, and scalable drug discovery strategies. Here, we present an artificial intelligence (AI)‐based ensemble framework to accelerate the identification of small‐molecule inhibitors against therapeutic targets. As a case study, we applied this approach to HIV‐1 reverse transcriptase (HIV‐1 RT), an essential enzyme in viral replication. Our stacking ensemble model, trained on a curated ChEMBL dataset, achieved high predictive performance (90.3% accuracy, 89.4% ROC‐AUC) and was used to screen the Natural Products Atlas (NPA) database. Promising hits were evaluated through physicochemical and ADMET filters, molecular docking, and 1 µs molecular dynamics (MD) simulations. Compound NP1, which exhibited stable binding to the NNRTI binding pocket, outperformed the FDA‐approved drug doravirine in post‐MD characterizations. Network analysis further suggested potential allosteric regulation via residues N136 and E138. This flexible AI‐MD pipeline provides an efficient strategy for discovering and repurposing inhibitors, with broad applicability to other therapeutic targets.

2023-12-11·Animal biotechnology

Effect of food supplementation on in vitro embryo production and growth performance in prepubertal Nelore heifers

Article

作者: Martins, Carlos Frederico ; Pivato, Ivo ; Eifert, Eduardo da Costa ; Guimarães, Roberto ; Magnabosco, Cláudio Ulhoa ; de Toledo, Ricardo Braz ; Oliveira, Rodrigo Vidal ; de Faria, Otávio Augusto Costa ; Dode, Margot Alves Nunes ; Malaquias, Juaci Vitoria ; dos Santos, Isabella Rodrigues ; Leme, Ligiane Oliveira

In vitro embryos production from prepubertal heifers can help contribute to breeding programs; however, strategies are necessary to increase their embryo production. The aim of this study was to investigate the effects of two nutritional plans on oocyte recovery, embryo production and growth performance of prepubertal Nelore heifers. Thirty-four Nelore heifers with age of 6.5 months were divided into two feeding treatments (NP1 and NP2). The NP1 diets served as the control and NP2 diets were formulated to contain an average of 1.22-fold more energy than NP1. After 3 months of supplementation, the animals underwent follicular aspiration (ovum pick-up, OPU) every 21 d for 3 months and embryos were produced in vitro. Wither height, chest depth, body weight and subcutaneous fat of animals were measured. The number of retrieved and viable oocytes per OPU were 1.49-fold and 1.42-fold greater in NP2 heifers (p = 0.018 and p = 0.049, respectively) than those in NP1 heifers. Heifers administered NP2 produced 29.7% blastocysts, a percentage higher than NP1 animals that produced 24.40% embryos (p < 0.05). Consequently, females in the NP2 treatment showed improved body development. These results indicate a positive effect of a higher energy diet on assisted reproduction and body development in prepubertal heifers.

2022-12-27·ACS nano

Targeting Cell Membranes, Depleting ROS by Dithiane and Thioketal-Containing Polymers with Pendant Cholesterols Delivering Necrostatin-1 for Glaucoma Treatment

Article

作者: You, Mengling ; Zhou, Xuezhi ; Ji, Dan ; Li, Haibo ; Zeng, Zhou ; Liang, Ganghao ; Xia, Xiaobo ; Liang, Zhuotao ; Rong, Rong ; Xiao, Haihua

Glaucoma is the leading cause of irreversible blindness worldwide, characterized by progressive vision loss due to the selective damage to retinal ganglion cells (RGCs) and their axons. Oxidative stress is generally believed as one key factor of RGCs death. Recently, necroptosis was identified to play a key role in glaucomatous injury. Therefore, depletion of reactive oxygen species (ROS) and inhibition of necroptosis in RGCs has become one of treatment strategies for glaucoma. However, existing drugs without efficient drug enter into the retina and have controlled release due to a short drug retention. Herein, we designed a glaucomatous microenvironment-responsive drug carrier polymer, which is characterized by the presence of thioketal bonds and 1,4-dithiane unit in the main chain for depleting ROS as well as the pendant cholesterols for targeting cell membranes. This polymer was adopted to encapsulate an inhibitor of necroptosis, necrostatin-1, into nanoparticles (designated as NP1). NP1 with superior biosafety could scavenge ROS in RGCs both in vitro and in vivo of an acute pathological glaucomatous injury model. Further, NP1 was found to effectively inhibit the upregulation of the necroptosis pathway, reducing the death of RGCs. The findings in this study exemplified the use of nanomaterials as potential strategies to treat glaucoma.

项与阿米替林/氯胺酮相关的新闻（医药）

2026-08-15

·复盘成就翻盘

【行业分析】一只猴 20 万，揭开了 CXO 最狠的一门生意

去年此刻，所有人都在问同一个问题：药明会不会被美国一纸禁令直接打死？一年过去，答案有点反常识——药明康德上半年狂赚 110 亿，毛利率冲到 52%，股价悄悄修复了一大截。比这更刺激的，是藏在它背后的那条产业链：真正卡住全球减肥药脖子的，不是某个神药，而是一根多肽反应釜，和一只卖到 20 万元的猴子。先说人话。什么叫 CXO？药企不想自己养几百个化学家、养一堆猴、做三年实验，就把"研发+生产"外包出去。管研发的叫 CRO，管生产的叫 CDMO。CXO 就是医药圈的"卖水人"——不管谁淘金，它都收这份辛苦钱。过去两年 CXO 跌成狗，根子在钱。Biotech 融不到资，砍订单、砍管线，上游外包自然跟着饿肚子。但 2026 年剧本反过来了：上半年全球医疗健康投融资 321 亿美元，中国创新药对外授权高达 997 亿美元，已经超过 2024 全年。钱一回来，最先回暖的一定是外包——因为药企的预算，会先变成 CXO 的订单。可真正让人心跳加速的，是 GLP-1（就是那波减肥针）。替尔泊肽一年卖出 164 亿美元，司美格鲁肽破百亿。但很多人没看透：药不是瓶颈，多肽原料药和 CDMO 才是。为什么？全球 GLP-1 多肽 2025-2027 年产能缺口约 300-400 吨/年，而单公斤多肽 CDMO 值 1.8-2.5 万美元，是小分子原料药的 5-8 倍。更狠的是，扩一条多肽产线要 12-24 个月，良率还得慢慢爬。换句话说——这不是谁想干都能干的生意。谁卡住了这两端？看数据就懂。药明康德的多肽业务（TIDES）上半年收入 72.6 亿、同比增长 44%；凯莱英的化学大分子 CDMO 订单同比翻了 1.27 倍；昭衍新药靠安评（离不开实验猴）净利预增最高 13 倍，实验猴价格直接飙到 20 万/只。所以这一轮 CXO，不是简单的"困境反转"。它是被 GLP-1 和出海重新定价的一次"卖水人"重估——产业链上最肥的环节，不在终端药，而在多肽产能和实验猴这两道咽喉。但有一件事，我必须泼盆冷水。药明康德今年 6 月被美国列入 1260H 清单，已然起诉；而真正的"大考"在 2026 年 12 月 18 日——OMB 首批"受关注生物技术公司"名单会不会把它写进去。这也是为什么它业绩炸裂，估值却始终差一口气。所以这一轮，别用"周期股反弹"的老眼光看 CXO。它更像被重新发现的"卖铲人"——淘金热里，最稳的永远是把铲子递给你的人。但记住两件事：多肽产能 2026-2027 年集中释放后，价格战会不会来？12 月那份名单会不会翻盘？这两个问题，决定你是吃肉，还是站岗。核心发现 · Core Findings（结论先行）周期位置： 2026 年 CXO 进入「外需回暖 + 内需复苏 + 中报兑现」三重共振的上行通道；全球 CXO 龙头在手订单同比 +25.2%，实验用食蟹猴价格飙至 20 万元/只，临床前 CRO 新签订单同比 +118%~+127%（中信建投，2026-07-24）。★ 咽喉瓶颈：S1 GLP-1 / 多肽 CDMO（TIDES）——全球 2025-2027 产能缺口约 300-400 吨/年，单公斤价值量 1.8-2.5 万美元（为小分子 API 的 5-8 倍），扩产需 12-24 个月且技术/认证壁垒高，是价值捕获最确定环节。价值捕获：药明康德 TIDES 业务 2026H1 收入 72.6 亿元（+44.3% YoY）；凯莱英化学大分子 CDMO 2025 收入 +123.7%、在手订单 +127.6%。龙头凭借「全产业链 + 成本比 Lonza/同行低 30-40%」锁定份额。最大风险：美国政策——BIOSECURE 法案已于 2025-12-18 作为 FY2026 NDAA 第 851 条成法；药明康德于 2026-06-08 被列入 DoD 1260H 清单并提起联邦诉讼（报道称 2026-08-08 获临时禁令）。OMB 首批「受关注生物技术公司(BCC)」名单 2026-12-18 前出炉，是真正的政策大考。闭环：创新药研发支出扩张（需求）→ 多肽/CDMO 产能与技术供给受限（约束）→ 头部 CRDMO 锁定溢价与订单（价值捕获）→ 药明康德 / 药明生物 / 凯莱英 / 泰格医药 / 昭衍新药（核心公司）。数据来源与证据等级 · Sources & Evidence Levels财务/公告/一致预期：westock-data（腾讯自选股金融数据），A 股 12 家 CXO 公司 2024-2026H1 财报、公告列表、卖方一致预期（取数 2026-08-13）。政策与行业：BIOSECURE / 1260H（多源媒体与公告交叉验证，2025-12-18 至 2026-08-08）；行业研报（中信建投《CXO：板块 BETA 稳中向好》2026-07-24；新浪财经行业报告 2026）、证券时报、华尔街见闻、腾讯新闻等。标注规则：A 公告/年报/半年报 B 调研/互动 C 研报/媒体；未达一手来源处标注「待核验」。一、产业链全景拆解 Panorama — BOM by Layer 医药 CXO = 医药研发与生产外包（Contract X Organization）。按「终端需求 → 上游要素」反向拆解，可分为上游要素（资源/产能/设备）、中游服务（CRO+CDMO）、下游客户（药企）与终端应用四层。价值流向：下游研发预算转化为中游外包订单，瓶颈卡在上游稀缺资源（实验猴、多肽固相合成产能）。说明：红框为供给约束环节；★ 标记 S1 级咽喉瓶颈（多肽 CDMO）。各段典型毛利率区间参考 2025 年报：CRO 发现 50-55%（成都先导 54.2%）、临床前安评 20-28%、临床 CRO 27-34%、小分子 CDMO 35-47%、多肽/大分子 CDMO 40-53%。二、关键环节筛选 Bottleneck Screening — Four Criteria 环节 Segment 高增长>行业CAGR 高利润毛利率高壁垒供给受限评级代表公司多肽/寡核苷酸 CDMO（TIDES） GLP-1 driven ✓ (+40~96%) ✓ (40-53%) ✓ 技术+FDA/EMA认证 ✓ 缺口300-400吨/年·扩产12-24月★ 咽喉点 S1 药明康德、凯莱英、诺泰、九洲实验用猴（食蟹猴·安评） ✓ 价格上行 ✓ 涨价弹性 ✓ 繁育资质+周期 ✓ 供需缺口S3 昭衍新药、美迪西（下游受益）药物发现（DEL 库等） △ ✓ (50%+) ✓ 超大规模库护城河 △S2 药明康德（DEL>1200亿分子）、成都先导临床 CRO（多中心/数统） ✓ 量价齐升 △ (27-34%) ✓ 人才+客户认证 △ 竞争分散S2 泰格医药、诺思格、普蕊斯大分子/ADC CDMO ✓ ✓ (45%+) ✓ △ 产能扩张快S2 药明生物、臻格、澳斯康小分子 CDMO ✓ ✓ (35-47%) △ △ 产能充足S3 药明康德、凯莱英、九洲、博腾瓶颈五维校验 · Five-Dimension Bottleneck Check（以 GLP-1 多肽 CDMO 环节为单位）维度评分判定依据供给弹性（扩产/格局）5/5 扩产 12-24 月、良率爬坡难；全球寡头（药明/凯莱英/诺泰 vs Bachem/CordenPharma），中国主导多肽 CDMO 产能 N 阶传导（与终端需求）5/5 每款 GLP-1 药物必消耗多肽 API/CDMO，量价线性挂钩；口服剂型剂量为注射剂数十~百倍，进一步放大 API 需求瓶颈紧张度4/5 全球缺口 2025-2027 约 300-400 吨/年，单公斤 1.8-2.5 万美元；药明 TIDES 在手订单 2025 末 +20.2% 机构盲区2/5 药明康德为大市值、机构密集覆盖（49 家一致预期），非盲区；但细分多肽产能/订单数据为预期差所在地缘杠杆4/5 中国主动主导全球多肽 CDMO（药明 TIDES 2025 营收 113.7 亿超三家欧洲龙头之和），但受美国政策反向压制合计 20/25 → 真瓶颈（True Bottleneck）确认；但属「服务/产能型」而非纯消耗材料，需跟踪产能过剩拐点。三、供需关系与竞争格局 Supply / Demand & Competition需求侧 DemandGLP-1 爆发：替尔泊肽 2024 全球销售 164.6 亿美元（翻倍），司美格鲁肽破百亿；口服 GLP-1（如 orforglipron）将放大原料药需求数十倍。C 媒体/研报融资回暖： 2026H1 全球医疗健康投融资 321.44 亿美元、963 起；全球 CXO 龙头在手订单 +25.2% YoY。C 媒体中国 BD 出海： 2026H1 创新药对外授权 997 亿美元（超 2024 全年）；2025 全年 1356.55 亿美元（+160%）。C 媒体外包渗透率：全球新药研发外包率预计 52%(2024)→57%(2026)。C 研报供给侧 Supply产能缺口：全球 GLP-1 多肽 2025-2027 产能缺口约 300-400 吨/年；中国多肽 API 总产能 2025 底约 25,000 kg。C 研报龙头扩产：药明康德多肽固相合成 2025 >10 万升→2026 冲 13 万升；凯莱英 2.1 万升(2024)→2026 底 6.9 万升。B 投资者活动自建分流：礼来 270 亿美元美国建 4 厂、诺和天津追加投资；三星生物 18 亿美元收购切入多肽。C 媒体替代风险： MNC「双源/去风险」分散下单（印度+中国+欧洲），长期结构性趋势。C 媒体四、候选公司证据复筛表 Company Evidence Re-Screening 公司 / 代码对应环节业务纯度公开证据（A/B/C）证据等级归类药明康德 sh603259 / hk02359 全产业链 CRDMO（发现+CDMO+临床），TIDES 核心极高 2025 营收 454.56 亿、NP 191.5 亿、GM 47.6%；2026H1 营收 288.97 亿、NP 110.8 亿、GM 52.3%，上调全年指引至 585-605 亿；TIDES 2026H1 收入 72.6 亿(+44.3%)；美国客户收入占比 ~72%(2025 年报)；1260H 诉讼公告A 年报/半年报/公告重点线索药明生物 hk02269 大分子 CDMO（单抗/ADC/融合蛋白）极高全球大分子 CDMO 龙头，跟随 GLP-1 多肽/ADC 高景气；行业研报列为 CDMO 核心受益C 研报/行业地位重点线索凯莱英 sz002821 / hk06821 小分子+多肽 CDMO 极高 2025 营收 66.7 亿、NP 11.33 亿、GM 42%；化学大分子 CDMO 2025 收入 10.28 亿(+123.7%)、在手订单 +127.6%(年报)；多肽产能 2026 底 6.9 万升(投资者活动)；2026 H 股股权激励公告A 年报/公告 B 调研重点线索泰格医药 sz300347 / hk03347 临床 CRO 龙头极高 2025 营收 68.33 亿、NP 8.88 亿(较 2024 的 4.05 亿翻倍)、GM 27.4%；2026-08-03 回购进展公告、2025 年度权益分派A 年报/公告重点线索昭衍新药 sh603127 / hk06127 临床前安评 CRO（依赖实验猴）极高 2025 营收 16.58 亿、NP 2.98 亿；2026H1 预告归母净利 6-9 亿(+884%~1377%，公告)；新签订单 25Q3/25Q4/26Q1 同比 +24%/+118%/+112%(研报)A 年报/预告 C 研报重点线索康龙化成 sz300759 / hk03759 全流程 CRO+CDMO 高 2025 营收 140.95 亿、NP 16.64 亿、GM 34.8%；与礼来战略合作支持 orforglipron 中国本地化供应(媒体)A 年报 C 媒体重点线索博腾股份 sz300363 小分子+多肽 CDMO 高 2025 营收 34.2 亿、NP 0.96 亿(扭亏，2024 为 -2.88 亿)、GM 29.9%；2026H1 业绩预告(2026-07-14)、取得药品生产许可证(2026-08-03)、回购完毕；股东取保候审公告(2026-07-22)A 年报/预告/公告观察线索九洲药业 sh603456 小分子 CDMO+多肽(800kg/年 GMP) 高 2025 营收 55.09 亿、NP 7.30 亿、GM 36.9%；多肽处产能爬坡A 年报观察线索药石科技 sz300725 药物发现(分子砌块)+CDMO 高 2025 营收 19.74 亿、NP 1.84 亿、GM 30.8%A 年报观察线索美迪西 sh688202 临床前 CRO 高 2025 营收 11.63 亿、NP -1.68 亿(亏损收窄，2024 为 -3.31 亿)；2026H1 预告扭亏(公告)A 年报/预告观察线索普洛药业 sz000739 原料药+CDMO+多肽爬坡中高 2025 营收 97.84 亿、NP 8.91 亿、GM 26.4%；多肽车间推进中A 年报观察线索成都先导 sh688222 DEL 库(药物发现细分) 高(细分) 2025 营收 5.26 亿、NP 1.10 亿、GM 54.2%(高毛利 niche 隐形冠军)A 年报观察线索注：归类仅三档——重点线索 / 观察线索 / 暂不适合作为案例；研报热度仅作市场关注度线索，不作业绩证明。港股财务以行业研报与公告交叉验证，未逐期拉取结构化财报。五、重点线索财务拐点 Financial Inflection (2024 → 2025 → 2026H1) 下图为 A 股 12 家 CXO 公司 2025 年营业收入（亿元）与 2025 年净利率（%）对比（数据源：westock-data 财报，A 级）。红柱=营收，蓝/绿柱=净利率（红涨绿跌语义仅用于涨跌指示，此处表示盈利为正）。公司财务拐点评级依据（2024→2025→2026H1）药明康德★★★★★ 超级拐点 GM 41.5→47.6→52.3%；NP 94.5→191.5→110.8(亿)；TIDES +44.3%；CapEx 上调至 75-85 亿昭衍新药★★★★★ 超级拐点 NP 0.74→2.98→H1 预告 6-9 亿；安评订单 +118%~+127%；实验猴紧缺泰格医药★★★★ 明确拐点 NP 4.05→8.88 亿翻倍；临床 CRO 价格底部回升、新签订单恢复凯莱英★★★☆ 早期拐点 NP 9.49→11.33 亿稳健；大分子 CDMO 高增，但整体利润弹性待释放康龙化成★★★☆ 早期拐点营收 122.8→140.95 亿增；NP 17.93→16.64 略降（投入期），关注毛利率修复博腾/美迪西★★★☆ 早期拐点博腾扭亏(0.96 亿)、美迪西 H1 预告扭亏；基础仍薄，验证中六、红队反向证伪 Red-Team Refutation 公司最大潜在风险现有证据能否缓解缺失关键数据风险等级药明康德美国政策（1260H 已列名 + OMB BCC 名单 2026-12-18 大考）；客户「双源/去风险」分流；GLP-1 产能过剩价格战部分缓解：PI 临时禁令(报道)、祖父条款覆盖存量、3-5 年过渡期、诉讼抗辩 OMB 12/18 是否纳入、上诉结果、美国客户占比实时变化高凯莱英 / 多肽 CDMO GLP-1 需求不及预期 → 2026-2027 产能集中释放致价格战；礼来/诺和自建+三星生物切入部分缓解：订单 backlog +127.6%、过半境外、客户黏性全球 GLP-1 真实需求曲线、产能利用率中泰格医药国内临床 CRO 价格战、临床试验延期；地缘影响小（国内为主）缓解：行业价格已触底回升、新签订单恢复单笔订单价格趋势中昭衍新药实验猴供给恢复后安评价格回落；下游 Biotech 融资波动缓解：订单高增锁定、产能利用率提升食蟹猴价格后续走势中博腾股份扭亏基础薄弱、大客户集中；股东取保候审事件(2026-07-22) 弱：业绩刚转正，确定性低于龙头大客户订单持续性、治理稳定性中高七、动态跟踪与熔断里程碑 Tracking Milestones & Circuit-Breaker 公司跟踪里程碑（未来两季度）最晚观察时间达成 = 信号未达成 = 信号药明康德 ① OMB 首批 BCC 名单是否纳入药明；② 2026 全年 TIDES 收入达 120-130 亿指引；③ 美国客户收入占比变化 2026-12-31 未入 BCC / TIDES 达标 → 地缘期权兑现、估值修复入 BCC 且无祖父条款覆盖新增 → 降级「失效观察」凯莱英 ① 2026 底多肽产能达 6.9 万升；② 大分子 CDMO 新签订单增速维持 >50%；③ GLP-1 相关订单落地 2026-12-31 产能+订单双兑现 → 多肽第二极确认产能利用率偏低 / 订单放缓 → 评估过剩风险泰格医药 ① 新签订单价格回升确认；② 国内临床 CRO 价格战缓和 2026-12-31 量价齐升 → 利润率修复价格续降 → 竞争加剧、降级权重昭衍新药 ① 2026H1 净利兑现 6-9 亿；② 实验猴价格走势；③ 新签订单增速维持 2026-10-31 兑现 → 安评高景气确认不及预期 → 价格战/需求证伪博腾股份 ① 2026H1 业绩预告兑现（扭亏/增长）；② 多肽产能爬坡；③ 大客户订单 2026-10-31 持续盈利 → 困境反转确认再度亏损 → 降级观察熔断规则（研究跟踪用，非交易指令）： 🔴 红色：关键里程碑未按时达成 → 降为「失效观察」，若持仓提示复核论点（由用户自行决策）。 🟠 橙色：连续两季度未达成 → 降低研究权重。 ⚫ 系统级：行业/政策黑天鹅（如 BCC 名单实质落地、地缘升级）→ 立即复核全部线索、转向防守取向（非「清仓」指令）。八、防幻觉检查 Anti-Hallucination Check 可能被夸大的结论修正后严谨表述「药明康德是全球多肽 CDMO 绝对垄断者」药明 TIDES 2025 营收 113.7 亿确超 Bachem/CordenPharma/PolyPeptide 三家欧洲龙头之和（C 媒体），但属「一超多强」，凯莱英/诺泰紧追，且 MNC 自建+三星生物切入分流，非垄断。「美国客户占比 72% 意味着随时被切断」 72% 来自 2025 年报（A），但 BIOSECURE 限制对象是联邦采购/合同资金流，非私营商业合作；祖父条款覆盖存量。风险真实但非「一刀切切断」。「初步禁令 = 药明彻底胜诉」 2026-08-08 初步禁令（PI）为程序性临时救济、来源层级偏低（C 媒体，待核验）；OMB 12/18 BCC 名单为独立路径，不受 PI 约束。终局未定。「CXO 整体高景气、闭眼买」分化显著：龙头（药明/凯莱英/泰格/昭衍）拐点清晰，但美迪西/博腾/睿智仍薄利或亏损，GLP-1 产能 2026-2027 集中释放后存价格战隐忧。须个股甄别。市值/估值数字当作实时市值 3834 亿、PE 19-20x 等为媒体/一致预期时点数据（2026-08），非实时行情；本报告财务以 2025 年报/2026H1 为准。九、五维星级评级与分梯队 Five-Star Rating & Tiers 梯队 Tier 公司逻辑硬度一句话逻辑第一梯队 ⭐⭐⭐⭐⭐ 药明康德、药明生物全产业链 + 多肽/大分子双卡位 + 成本优势；药明系享地缘期权（也承担地缘风险）全球 CRDMO 平台，TIDES 与商业化 CDMO 同时受益 GLP-1 与外包率提升第二梯队 ⭐⭐⭐⭐ 凯莱英、泰格医药、昭衍新药、康龙化成关键卡位：多肽 CDMO / 临床 CRO 龙头 / 安评 / 全流程各自细分赛道供需缺口明确、订单高增、拐点清晰观察/防守 ⭐⭐⭐ 博腾、九洲、药石、美迪西、普洛、成都先导受益但非核心增量或弹性待验证多肽爬坡 / 分子砌块 / 扭亏验证 / 高毛利 niche；需里程碑跟踪一句话总结闭环 · One-Line Loop【创新药研发支出扩张（需求增长）→ 多肽/CDMO 产能与技术供给受限（供给约束）→ 头部 CRDMO 锁定溢价与订单（价值捕获）→ 药明康德 / 药明生物 / 凯莱英 / 泰格医药 / 昭衍新药（核心公司）】Demand expansion → Supply-constrained TIDES/CDMO → Value capture by leading CRDMOs → WuXi AppTec / WuXi Biologics / Asymchem / Tigermed / Joinn.附：重点线索公司卡片 Key Company Cards (Evidence-Tagged)药明康德 sh603259 / hk02359 · 证据等级 A药明康德 WuXi AppTec A 年报/半年报/公告全球 CRDMO 平台龙头，业务贯穿药物发现→CDMO→临床。TIDES（多肽/寡核苷酸）为核心 α：2026H1 收入 72.6 亿(+44.3%)，全年指引 120-130 亿。美国客户收入占比 ~72%(2025 年报)。产业逻辑⭐⭐⭐⭐⭐ 增量空间⭐⭐⭐⭐⭐ 不可替代性⭐⭐⭐⭐⭐ 技术壁垒⭐⭐⭐⭐⭐ 不可复制性⭐⭐⭐⭐ 跟踪里程碑：OMB BCC 名单(2026-12-18) · TIDES 全年 120-130 亿 · 美国客户占比变化。关键日期 2026-12-18凯莱英 sz002821 / hk06821 · 证据等级 A/B凯莱英 Asymchem A 年报B 调研小分子+多肽 CDMO 双轮。化学大分子 CDMO 2025 收入 10.28 亿(+123.7%)、在手订单 +127.6%；多肽固相合成产能 2024 2.1 万升→2026 底 6.9 万升。服务临床多肽药 52 个（减重 19 个）。产业逻辑⭐⭐⭐⭐ 增量空间⭐⭐⭐⭐⭐ 不可替代性⭐⭐⭐⭐ 技术壁垒⭐⭐⭐⭐ 不可复制性⭐⭐⭐ 跟踪里程碑：2026 底多肽产能 6.9 万升 · 大分子新签订单 >50% · GLP-1 订单落地。泰格医药 sz300347 / hk03347 · 证据等级 A泰格医药 Tigermed A 年报/公告临床 CRO 龙头（国内市占 ~25%+）。2025 NP 8.88 亿(较 2024 4.05 亿翻倍)；临床 CRO 价格底部回升、新签订单恢复。地缘影响小（国内为主）。产业逻辑⭐⭐⭐⭐ 增量空间⭐⭐⭐⭐ 不可替代性⭐⭐⭐⭐ 技术壁垒⭐⭐⭐ 不可复制性⭐⭐⭐ 跟踪里程碑：新签订单价格回升确认 · 国内临床 CRO 价格战缓和。昭衍新药 sh603127 / hk06127 · 证据等级 A/C昭衍新药 Joinn A 年报/预告C 研报临床前安评 CRO 龙头，直接受益实验猴紧缺与安评订单高增。2026H1 预告归母净利 6-9 亿(+884%~1377%)；新签订单 25Q3/25Q4/26Q1 同比 +24%/+118%/+112%。产业逻辑⭐⭐⭐⭐ 增量空间⭐⭐⭐⭐⭐ 不可替代性⭐⭐⭐⭐ 技术壁垒⭐⭐⭐ 不可复制性⭐⭐⭐ 跟踪里程碑：2026H1 净利兑现 6-9 亿 · 食蟹猴价格走势 · 新签订单增速。康龙化成 sz300759 / hk03759 · 证据等级 A/C康龙化成 Pharmaron A 年报C 媒体全流程 CRO+CDMO，与礼来战略合作支持 orforglipron 中国本地化供应。2025 营收 140.95 亿、NP 16.64 亿、GM 34.8%。产业逻辑⭐⭐⭐⭐ 增量空间⭐⭐⭐⭐ 不可替代性⭐⭐⭐⭐ 技术壁垒⭐⭐⭐⭐ 不可复制性⭐⭐⭐ 跟踪里程碑：毛利率修复 · 与礼来合作订单兑现 · 新签订单回暖。免责声明 · Disclaimer本报告由产业链研究方法论自动生成，所有财务数据来自 westock-data（腾讯自选股）公开财报/公告，行业与政策信息来自公开研报与媒体并标注来源与证据等级，力求真实但非投资顾问意见。报告不构成任何买入/卖出/目标价/仓位建议，亦不构成交易指令；熔断规则仅用于研究跟踪与风险提示。市场有风险，决策需基于个人独立判断并咨询持牌专业人士。数据截至 2026-08-13，部分媒体数据存在时点滞后，请以最新官方披露为准。

2024-08-26

·PRNewswire

Kanazawa University research: High-speed atomic force microscopy reveals dynamic behavior of brain receptors

KANAZAWA, Japan, Aug. 26, 2024 /PRNewswire/ -- Researchers at the Nano Life Science Institute (WPI-NanoLSI), Kanazawa University, used high-speed atomic force microscopy to observe dynamic changes in AMPA receptors, which are vital for brain communication. Their findings, published in ACS Nano, reveal how these receptors adapt during signal transmission and suggest potential targets for neurological therapies. This study, led by Mikihiro Shibata, delves into the complex behavior of AMPA receptors (AMPARs), which are vital for communication between nerve cells in the brain. AMPARs are responsible for fast excitatory neurotransmission, a process crucial for learning, memory, and overall cognitive function. The research particularly focuses on the GluA2 subunit of AMPARs, a key component in transmitting signals at synapses, the junctions where neurons connect. The team employed an advanced imaging technique known as high-speed atomic force microscopy (HS-AFM) to observe the real-time behavior of the N-terminal domain (NTD) in the GluA2 subunit. The NTD is the starting segment of the protein, playing a critical role in how AMPARs function and cluster at synapses. The study also examined how the GluA2 subunit interacts with TARP γ2, a regulatory protein that fine-tunes the receptor's response to signals. One of the key findings is the behavior of the NTD in different states: resting, activated, and desensitized. The researchers discovered that in the activated state, the NTD dimers—pairs of NTDs—can split into single units or monomers. This process, known as subunit exchange, allows parts of one receptor to s another, potentially altering the receptor's function. This novel observation was supported by molecular dynamics simulations, which showed that these monomeric states are stable in their lipid environment, providing a potential mechanism for receptor adaptability and diversity. In the desensitized state, where the receptor becomes less responsive to signals, the NTD dimers separate, but their movement is more restricted compared to the activated state. This desensitization helps protect nerve cells from overstimulation, which could lead to cellular damage. The study's insights into the structural changes of the NTDs in different functional states highlight the dynamic nature of AMPARs and their ability to adapt to various conditions within the synaptic environment. The research also sheds light on the role of neuronal pentraxin 1 (NP1), a protein that aids in the clustering of AMPARs at synapses. NP1 forms a ring-shaped structure that binds to the tips of the NTDs, potentially facilitating the gathering of multiple AMPARs into clusters. This clustering is essential for efficient synaptic transmission, as it brings receptors closer together, allowing for more effective signaling between neurons. By linking multiple receptors, NP1 enhances the strength and reliability of the synaptic connection, contributing to the overall efficiency of neural communication. The study's findings contribute significantly to our understanding of how AMPARs function and adapt during neurotransmission. By revealing the dynamic structural changes in the NTDs and highlighting the role of NP1 in receptor clustering, the research offers new insights into the molecular processes that underlie synaptic plasticity—the ability of synapses to strengthen or weaken over time, which is essential for learning and memory. These discoveries could have important implications for developing treatments for neurological disorders where AMPAR function is disrupted, such as in epilepsy, Alzheimer's disease, and other cognitive impairments. As the authors conclude, "Our research reveals the dynamic structural changes that occur within AMPA receptors, underscoring their remarkable adaptability. Understanding these mechanisms not only deepens our knowledge of brain function but also opens new avenues for therapeutic interventions targeting synaptic transmission and plasticity." Glossary AMPA Receptors (AMPARs) Proteins on the surface of nerve cells essential for communication between cells in the brain. They respond to signals by allowing charged particles to enter the cell, triggering various processes like learning and memory formation. N-terminal domain (NTD) The beginning part of a protein that influences how the protein behaves and interacts with other molecules. For AMPARs, the NTD helps them cluster together at nerve cell connections. Synapse The point where two nerve cells connect and communicate, allowing signals to pass from one cell to another. TARP γ2 A regulatory protein that interacts with AMPARs to control their response to signals. High-speed atomic force microscopy (HS-AFM) This imaging technique uses a nanosized tip at the end of a cantilever that is scanned over a sample. It can be used to determine the topography of a sample surface from the change in the strength of forces between the tip and the sample with distance, and the resulting deflection of the cantilever. It was first developed in the 1980s but a number of modifications have augmented the functionality of the technique since. It is better suited to imaging biological samples than the scanning tunnelling microscope developed that had been developed because it does not require a conducting sample. In the 2000s Toshio Ando at Kanazawa University was able to improve the scanning speed to such an extent that moving images could be captured. This allowed people to use the technique to visualize molecular processes for the first time. Desensitized state A condition where the receptor becomes less responsive to signals, often to prevent overstimulation. Neuronal pentraxin 1 (NP1) A protein that clusters AMPARs at synapses, improving their signaling ability. Subunit exchange The process where parts of a protein (subunits) s receptors, potentially altering their function. Related figure and caption High-speed AFM directly visualized the real-space and real-time structural dynamics of AMPARs in the presence of ligands in a liquid environment. © 2024 Sumino, et al., ACS Nano Reference Ayumi Sumino, Takashi Sumikama, Yimeng Zhao, Holger Flechsig, Kenichi Umeda, Noriyuki Kodera, Hiroki Konno, Motoyuki Hattori, and Mikihiro Shibata, High-speed atomic force microscopy reveals dynamic dimer splitting of the N-terminal domain of GluA2 ionotropic glutamate receptor-auxiliary subunit complex, Published online 23 August 2024, ACS Nano 2024. DOI: 10.1021/acsnano.4c06295 URL: Funding acknowledgements This research was supported by the World Premier International Research Center Initiative (WPI), MEXT, Japan (to M.S.), JSPS KAKENHI grant numbers JP20K21122 (to M.S.) and JP21H01771 (to M.S.), JSPS Bilateral Program Number JP120247404 (to M.S.), the Mochida Memorial Foundation for Medical and Pharmaceutical Research (to M.S.), the Uehara Memorial Foundation (to M.S.), the National Natural Science Foundation of China (32071234, 32271244, 32250610205, and 32411540020 to M.H.), an innovative research team of high-level local universities in Shanghai and a key laboratory program of the Education Commission of Shanghai Municipality (ZDSYS14005 to M.H.), and JST/CREST (JPMJCR1762 to N.K. and H.F.). Contact Kimie Nishimura (Ms) Project Planning and Outreach NanoLSI Administration Office, Nano Life Science Institute (WPI-NanoLSI) Kanazawa University Kakuma-machi, Kanazawa 920-1192, Japan Email: [email protected] Tel: +81 (76) 234-4555 About Nano Life Science Institute (WPI-NanoLSI), Kanazawa University Understanding nanoscale mechanisms of life phenomena by exploring "uncharted nano-realms". Cells are the basic units of almost all life forms. We are developing nanoprobe technologies that allow direct imaging, analysis, and manipulation of the behavior and dynamics of important macromolecules in living organisms, such as proteins and nucleic acids, at the surface and interior of cells. We aim at acquiring a fundamental understanding of the various life phenomena at the nanoscale. About the World Premier International Research Center Initiative (WPI) The WPI program was launched in 2007 by Japan's Ministry of Education, Culture, Sports, Science and Technology (MEXT) to foster globally visible research centers boasting the highest standards and outstanding research environments. Numbering more than a dozen and operating at institutions throughout the country, these centers are given a high degree of autonomy, allowing them to engage in innovative modes of management and research. The program is administered by the Japan Society for the Promotion of Science (JSPS). See the latest research news from the centers at the WPI News Portal: Main WPI program site: About Kanazawa University As the leading comprehensive university on the Sea of Japan coast, Kanazawa University has contributed greatly to higher education and academic research in Japan since it was founded in 1949. The University has three colleges and 17 schools offering courses in subjects that include medicine, computer engineering, and humanities. The University is located on the coast of the Sea of Japan in Kanazawa – a city rich in history and culture. The city of Kanazawa has a highly respected intellectual profile since the time of the fiefdom (1598-1867). Kanazawa University is divided into two main campuses: Kakuma and Takaramachi for its approximately 10,200 students including 600 from overseas. SOURCE Kanazawa University

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