A Double-blind, Oral, Multiple-dose, Parallel, Randomized Study to Evaluate Efficacy and Safety of Endoxifen in Bipolar I Disorder Patients With Acute Mania Episodes With or Without Mixed Features

Bipolar disorder (BPD) is a chronic debilitating illness characterized by drastic swings in mood, energy and functional ability that affects the adult population. Endoxifen is an active metabolite of the marketed drug Tamoxifen and the present study aims to evaluate the efficacy and safety of 8 mg endoxifen in the Bipolar I disorder patient population compared to a placebo arm. Endoxifen will be compared to a placebo to demonstrate that the test product is active and to establish that the study is sufficiently sensitive to detect differences between the investigational products. Thus, Endoxifen will be compared to placebo to demonstrate that the test product is safe and active.

开始日期2024-03-19

申办/合作机构

Jina Pharmaceuticals, Inc.

[+1]

NCT06075953

/ Recruiting临床2期

DCIS: RECAST Trial -Ductal Carcinoma In Situ: Re-Evaluating Conditions for Active Surveillance Suitability as Treatment: a Breast Cancer Prevention Pilot Study

The goal of this trial is to see if active surveillance monitoring and hormonal therapy in patients diagnosed with ductal cell carcinoma in situ (DCIS), an early stage of breast cancer, can be an effective management of the disease.
Participants will be asked to receive control hormonal therapy or an investigational hormonal therapy treatment. Participants will be asked to return for evaluation with MRI at three months and six months. Depending on the evaluation participants will have the option to continue on the treatment. If the evaluation suggests surgery is recommended, the participant will discontinue the study treatment and will undergo surgery. In addition to the treatment and MRI evaluation, participants will be asked to provide blood sample to understand their immune status, provide saliva sample for genetic testing, provide the study with a portion of the tissue or slides generated from tissue removed during surgery performed as part of their standard of care.

开始日期2024-02-17

申办/合作机构

Quantumleap Healthcare Collaborative

100 项与内昔芬相关的临床结果

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100 项与内昔芬相关的转化医学

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100 项与内昔芬相关的专利（医药）

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项与内昔芬相关的文献（医药）

2026-08-01·REPRODUCTIVE TOXICOLOGY

The effect of long-term oral tamoxifen and metabolism in the mouse ovary

Article

作者: Louie, Stan ; Place, Trenton L ; Kutlutürk, Gülbahar Z ; Awadalla, Michael S ; Li, Zeyang ; Ingles, Sue Ann ; Danis, Rachel B ; Asante, Isaac ; Yu, Xiaohui ; McGinnis, Lynda K

Tamoxifen (TAM) is a selective estrogen receptor modulator (SERM) widely used as long-term chemotherapy for premenopausal women with estrogen-sensitive breast cancer. We developed a murine model of chronic TAM exposure by administering TAM admixed in mouse chow (TAM-chow), a less stressful and physiologically relevant alternative to daily gavage or injections. Mice received either 36 mg/kg/day or 72 mg/kg/day for 2 or 5 weeks. Body weights were monitored every 2-days; blood and tissue samples collected at endpoints. TAM and key metabolites (N-desmethyl-TAM (NDM-TAM), 4-hydroxytamoxifen (4-OH-TAM), and endoxifen isomers,) were quantified in serum and ovarian tissues using LC-MS/MS. The concentrations of TAM and metabolites showed dose-dependent trends: serum TAM levels increased with time, while ovarian levels remained relatively stable. Correlation analyses suggest that TAM, NDM-TAM, and Z-endoxifen are transported into the ovary with linear serum-ovary concentration relationships. 4-OH-TAM showed a significant monotonic association, but the relationship was not well described by a specific functional model. In contrast, E-endoxifen may reflect local ovarian metabolism involving CYP-mediated pathways. Estrogen receptor expression in ovarian tissue was dynamically regulated, where Esr1 increased significantly after 2-weeks and returned toward baseline by 5-weeks, while Esr2 showed a biphasic response with initial downregulation followed by upregulation at 5-weeks. Estrogen receptor Gpr30 was elevated across treatment groups, indicating sustained upregulation. Taken together, the TAM-chow model effectively simulates long-term oral TAM treatment, enabling detailed evaluation of ovarian TAM pharmacokinetics, metabolism, and estrogen signaling alterations. This approach offers a robust platform to study chronic TAM effects on female reproductive biology under clinically relevant conditions.

2026-05-01·Pharmacogenetics and Genomics

NFIB rs28379954 does not affect CYP2D6-mediated metabolism of prototypical substrates, tamoxifen or solanidine

Article

作者: Kim, Richard B. ; Medwid, Samantha ; Schwarz, Ute I.

Background:

Cytochrome P450 2D6 (CYP2D6) is a highly polymorphic drug-metabolizing enzyme involved in the metabolism of many clinically important medications. CYP2D6 is affected by genetic variation as well as drug interactions; however, this does not account for all the variability seen in CYP2D6. Previously, a single-nucleotide variant in the nuclear factor 1-B ( NFIB ), rs28379954 T>C, was linked to increased CYP2D6 activity and metabolism of CYP2D6 substrates. Thus, we investigated the effect of NFIB rs28379954 on the metabolism of CYP2D6 substrates, solanidine and tamoxifen.

Methods:

Patients ( N = 759) were genotyped for CYP2D6 genetic variants and NFIB rs28379954. Solanidine, tamoxifen, and their metabolites were measured with ultra-HPLC-tandem mass spectrometry.

Results:

NFIB rs28379954 genotype (T/T versus T/C) was not associated with metabolism of solanidine to its CYP2D6-generated metabolites, 4-OH-solanidine or SSDA irrespective of CYP2D6 phenotype (poor metabolizer, intermediate metabolizer, or normal metabolizer; P > 0.05). Similarly, the ratio of endoxifen to tamoxifen was not affected by NFIB rs28379954 genotype in any CYP2D6 phenotypic group ( P > 0.05). Multivariable linear regression modeling demonstrated that CYP2D6 phenotypes were associated with solanidine metabolic ratios as well endoxifen to tamoxifen ratios. However, the addition of NFIB genotype to the model did not significantly improve the predictability of solanidine or tamoxifen metabolites in plasma.

Conclusion:

In conclusion, we did not observe any significant impact of NFIB rs28379954 genetic variation on CYP2D6 activity in vivo , when assessed using tamoxifen or solanidine metabolites as prototypical CYP2D6 substrates.

2026-04-01·Indian Journal of Psychiatry

Endoxifen-induced ovarian hyperstimulation and galactorrhea in an adolescent with severe personality disorder

Letter

作者: Aggarwal, Mahak ; Aneja, Jitender ; Srileka, I J

项与内昔芬相关的新闻（医药）

11 小时之前

·BioSpace

Atossa Therapeutics Announces Publication of Novel (Z)-Endoxifen-Related Compounds Demonstrating Potent Anti-Cancer Activity in ER-Positive Breast Cancer

Peer-reviewed preclinical study published in npj Breast Cancer identifies new chemical entities with activity in ESR1-mutant models Findings suggest potential for combination with abemaciclib SEATTLE , July 28, 2026 /PRNewswire/ -- Atossa Therapeutics, Inc. (NASDAQ: ATOS) ("Atossa" or the "Company"), a clinical-stage biopharmaceutical company developing novel therapies in oncology and other areas of significant unmet clinical need, today announced the publication of a peer-reviewed preclinical study in npj Breast Cancer evaluating five novel chemical entities structurally related to (Z)-endoxifen. The study titled, "Novel (Z)-endoxifen-related new chemical entities exhibit potent anti-cancer activity in ERα+ breast cancer," reported anti-estrogenic and anti-cancer activity across multiple estrogen receptor-positive breast cancer models, including models harboring clinically relevant activating mutations in ESR1. Publication Details ezstandalone.cmd.push(function () { ezstandalone.showAds(131); }); Journal: npj Breast Cancer Publication Date: July 20, 2026 Article Title and Link: Novel (Z)-endoxifen-related new chemical entities exhibit potent anti-cancer activity in ERα+ breast cancer Research Collaboration: Mayo Clinic and Atossa Therapeutics, Inc. Summary The investigators evaluated five previously uncharacterized compounds generated during the synthesis of (Z)-endoxifen - AT416E, AT416Z, AT402E, AT402Z and AT300 - alongside (Z)-endoxifen in a broad panel of laboratory assays. The studies assessed two- and three-dimensional tumor-cell growth, apoptosis, cell-cycle progression, migration, invasion, estrogen receptor transcriptional activity, gene-expression changes and activity in combination with the CDK4/6 inhibitor abemaciclib. Several compounds demonstrated potent anti-estrogenic effects, and affected multiple anti-cancer processes including apoptosis, cell-cycle progression, migration, invasion and estrogen receptor-driven transcription. In certain experimental settings and models, selected compounds combined with abemaciclib demonstrated additive to synergistic activity that was comparable to or greater than the activity observed with abemaciclib plus (Z)-endoxifen. The compounds also showed activity in models containing activating ESR1 mutations, which are associated with endocrine resistance and recurrent or metastatic estrogen receptor-positive breast cancer. RNA-sequencing analyses identified shared anti-estrogenic effects as well as distinct compound-specific transcriptional programs that may help differentiate the candidates. The authors concluded that select compounds warrant further in vivo safety evaluation, as well as efficacy studies, including as potential second- or third-line approaches for recurrent disease. These findings are preclinical and do not establish safety or efficacy in patients. "This publication expands the scientific foundation of our endoxifen platform and identifies additional compounds with compelling activity across difficult-to-treat estrogen receptor-positive breast cancer models," said Dr. Steven C. Quay, M.D., Ph.D., President and Chief Executive Officer of Atossa Therapeutics. "Of particular interest is the activity observed in ESR1-mutant models and in combination with a CDK4/6 inhibitor. While these results are early and preclinical, we believe they provide a strong rationale for further evaluation of selected candidates as we continue to explore opportunities to address endocrine resistance and recurrent disease." About Estrogen Receptor-Positive Breast Cancer Estrogen receptor-positive breast cancer is the most common molecular subtype of breast cancer. Although endocrine therapies are effective for many patients, recurrence and late relapse remain important clinical challenges. Activating mutations in ESR1 can allow estrogen receptor signaling to continue despite estrogen deprivation and are a recognized mechanism of acquired resistance in advanced disease. New therapies capable of inhibiting estrogen receptor signaling in ESR1-mutant tumors, alone or in rational combinations, may help address this unmet need. About Atossa Therapeutics Atossa Therapeutics, Inc. (Nasdaq: ATOS) is a clinical-stage biopharmaceutical company developing innovative medicines in oncology and other areas of significant unmet need. The Company's lead product candidate, (Z)-endoxifen, is currently in development across several clinical settings. (Z)-endoxifen is a potent Selective Estrogen Receptor Modulator/Degrader (SERM/D) with demonstrated activity across multiple mechanisms of interest. Atossa is evaluating its potential applications in oncology and rare diseases. The Company's proprietary oral formulation has shown a favorable safety pro pharmacology distinct from tamoxifen, including ER-targeted effects and PKC inhibition. Atossa's (Z)-endoxifen is not approved for any indication. Atossa's (Z)-endoxifen program is supported by a growing global intellectual property portfolio, including multiple recently issued U.S. patents and numerous pending applications worldwide. More information is available at . Forward-Looking Statements This press release contains certain "forward-looking statements" within the meaning of applicable securities laws, including, but not limited to, our expectations regarding the Company's development and regulatory strategy and related milestones, including the potential indications that the Company may pursue for (Z)-endoxifen, the potential role of (Z)-endoxifen and (Z)-endoxifen-related compounds in endocrine therapies, the potential for (Z)-endoxifen to receive regulatory approval and the timing thereof, expectations regarding the design, enrollment, data, timing, results and outcomes of the Company's clinical studies, the potential clinical significance of preclinical data, and the potential market and growth opportunities for the Company. Words such as "expect," "potential," "continue," "may," "will," "should," "could," "would," "seek," "intend," "plan," "estimate," "anticipate," "believe," "design," "predict," "future," or other similar expressions or statements regarding intent, belief or current expectations, are forward-looking statements. Forward-looking statements in this press release are subject to risks and uncertainties that may cause actual results, outcomes, or the timing of actual results or outcomes to differ materially from those projected or anticipated, including, without limitation, risks and uncertainties associated with: our ability to successfully execute our strategy to shorten our clinical development timelines for our lead program, (Z)-endoxifen; expected timing, completion and results of our preclinical studies, clinical trials, and research and development programs; the unpredictable relationship between preclinical study results and clinical study results; the timing or likelihood of regulatory filings and approvals; the outcome or timing of necessary regulatory approvals; our ability to maintain compliance with Nasdaq listing requirements; our ability to establish and maintain intellectual property rights covering our products; the impact of general macroeconomic conditions on our business; our ability to raise capital; and other risks and uncertainties detailed from time to time in Atossa's filings with the SEC, including, without limitation, its Annual Reports on Form 10-K and Quarterly Reports on Form 10-Q. Forward-looking statements are presented as of the date of this press release. Except as required by law, we do not intend to update any forward-looking statements. View original content to download multimedia: SOURCE Atossa Therapeutics Inc

临床结果

2026-07-24

·化学改变生活笔记

生物医药小分子专利周报-W30

2026年7月WIPO最新小分子药物专利全景：RAS赛道扎堆，PROTAC与晶型齐发部分内容由豆包生成 2026年7月23日，WIPO公开了最新一批PCT国际专利申请。本期共梳理小分子药物相关专利68项（去重后），覆盖抗肿瘤、心血管、神经系统、代谢/糖尿病、神经退行、抗炎止痛、免疫七大治疗领域。本期小结 1. RAS赛道持续火热：阿斯利康（G12D）、Kestrel、临港实验室等多家机构同时公开RAS抑制剂专利，RAS靶点仍是抗肿瘤小分子最热门方向之一，大环结构成为重要设计思路。 2. PROTAC降解剂平台化：罗氏连发3篇TYK2 PROTAC降解剂，Kymera公布IRF5降解剂，降解剂技术从单一靶点走向平台化布局，覆盖肿瘤、自免、神经退行等多领域。 3. 恒瑞本周大爆发：6篇小分子专利（EGFR大环、AR、BTK×2、心肌肌球蛋白、GLP-1三重激动剂），覆盖肿瘤、心血管、代谢三大领域，展现全面管线布局。 4. 晶型制剂专利占比提升：歌礼GLP-1RA晶型、Prelude SMARCA2多晶型、Ipsen BRAF盐型、明慧JAK晶型等，晶型/盐型/制剂类专利成为药企保护管线的重要手段。 5. GLP-1赛道内卷加剧：歌礼小分子GLP-1RA晶型、恒瑞三重激动剂、豪森双激动剂、辉瑞降钙素/胰淀素受体激动剂、Orforglipron舌下喷雾……口服和非肽类GLP-1相关分子持续涌现，代谢领域竞争白热化。一、抗肿瘤领域（38项）抗肿瘤仍是小分子专利最集中的领域，本期共38项。靶点分布广泛，RAS、PARP、BTK、EGFR等成熟靶点持续有新分子入局，SMARCA2、MAT2A、USP1等新兴靶点也有新进展。国内企业江苏恒瑞医药 → EGFR抑制剂/降解剂 → WO/2026/153576 → 大环化合物。新型EGFR大环抑制剂，兼具抑制和降解双重作用机制，用于EGFR介导或依赖性疾病。江苏恒瑞医药 → AR（雄激素受体） → WO/2026/153393 → 取代环丁烷化合物。用于雄激素受体介导或依赖性疾病的治疗。江苏恒瑞医药 → BTK抑制剂/降解剂 → WO/2026/153355、WO/2026/153486 → 杂芳基化合物（两篇）。BTK抑制剂兼降解剂，用于BTK介导或依赖性疾病，本周恒瑞在BTK靶点布局两篇专利。鲁南制药集团 → 蛋白激酶抑制剂 → WO/2026/153461 → 取代芳香稠环化合物。广谱蛋白激酶抑制剂，用于蛋白激酶介导疾病。苏州浦合医药 → MAT2A抑制剂 → WO/2026/153427 → 多环化合物。甲硫氨酸腺苷转移酶2A（MAT2A）抑制剂，用于癌症治疗。江苏亚虹医药 → USP1抑制剂 → WO/2026/153418 → 小分子。泛素特异性蛋白酶1抑制剂，可与其他抗肿瘤药物联合使用。深圳海王医药研究院 → 阿比特龙衍生物 → WO/2026/152811 → 前药。阿比特龙前药衍生物，体内转化为活性物质，吸收好、血浆稳定性高，用于雄激素过多相关疾病。上海广晟生物 → 光敏剂 → WO/2026/152434、WO/2026/152439 → 线粒体靶向/生物素受体靶向（两篇）。两款肿瘤靶向光动力治疗光敏剂，分别靶向线粒体和生物素受体。 Artivila（深圳）创新中心 → 蛋白酶体抑制剂 → WO/2026/153115 → 硼酸化合物。优异的蛋白酶体抑制活性，对肿瘤和自身免疫病具有治疗效果。苏州亘禾生物 → 酰胺化合物 → WO/2026/153498 → 小分子。酰胺类化合物及其药物组合物。临港实验室 → RAS抑制剂 → WO/2026/153217 → 大环化合物。大环RAS抑制剂，用于预防和/或治疗RAS突变肿瘤。中山药物发现研究院（中科院上海药物所） → HsClpP激动剂 → WO/2026/153207 → 1,2,4,5-四取代嘧啶酮。人酪蛋白水解酶P（HsClpP）激动剂，用于HsClpP介导疾病。海外企业与机构 AstraZeneca（阿斯利康） → KRAS G12D抑制剂 → WO/2026/154081 → 7-氟-5-甲氧基-2,3-二氢-[1,3]恶嗪并[4,5,6-de]喹唑啉衍生物。特异性靶向G12D突变Ras蛋白的抑制剂。 Kestrel Therapeutics → KRAS（K-Ras）抑制剂 → WO/2026/156118 → 小分子。Ras调节剂化合物，用于癌症治疗。 Ipsen Pharma → BRAF V600突变 → WO/2026/153964、WO/2026/153950 → 盐型/组合物（两篇）。BRAF V600突变黑色素瘤治疗化合物，包含盐酸盐、马来酸盐等多种盐型及羧酸组合物。 Prelude Therapeutics → SMARCA2 protac降解剂 → WO/2026/152359 → 游离碱和盐型多晶型。SMARCA2抑制剂多晶型，用于SMARCA2介导的癌症。 Nerviano Medical Sciences → PARP-1选择性抑制剂 → WO/2026/153970 → 联合用药。PARP-1选择性非捕获抑制剂与烷化剂或拓扑异构酶抑制剂组合，治疗肺癌、卵巢癌、胃癌等。 CV6 Therapeutics → PARP抑制剂+dUTPase抑制剂 → WO/2026/156174 → 三联疗法。PARP抑制剂、dUTPase抑制剂和胸苷酸生物合成抑制剂三联疗法。 Olema Pharmaceuticals → KAT6A/B抑制剂 → WO/2026/156325 → 小分子。KAT6A和KAT6B抑制剂用于癌症治疗。 Mission Therapeutics（英国） → USP30抑制剂 → WO/2026/154267 → N-氰基吡咯烷。去泛素化酶USP30抑制剂，用于癌症和线粒体功能障碍相关疾病。 Atossa Therapeutics → Endoxifen（恩多昔芬） → WO/2026/156303 → 小分子。(Z)-恩多昔芬组合物，用于他莫昔芬耐药的激素依赖性乳腺疾病、前列腺癌等。 Amgen Inc. → IGF-1R调节剂 → WO/2026/156056 → 小分子。胰岛素样生长因子1受体调节剂。 Immunome, Inc. → FAP靶向放射性核素 → WO/2026/156254 → 核药螯合化合物。成纤维细胞活化蛋白（FAP）靶向化合物，可螯合治疗性或诊断性放射性核素。 Tufts学院 → FAP靶向氰基脯氨酸 → WO/2026/156207 → 放射诊疗剂。FAP抑制剂氰基脯氨酸化合物，用于癌症放射诊疗。 Alpha-9 Oncology → NTSR1靶向化合物 → WO/2026/152218 → 放射性标记。神经降压素受体1靶向化合物及放射性标记形式，用于成像或放射治疗。 St. Jude儿童研究医院 → BCL11基因 → WO/2026/156221 → 噻唑类化合物。影响BCL11活性的噻唑类化合物。捷克有机化学与生化研究所 → CD73抑制剂 → WO/2026/153596 → 6-(杂)芳基-7-脱氮嘌呤核苷双膦酸酯。CD73抑制剂，用于病理性细胞增殖和免疫系统失调。 Albert Einstein医学院 → KRAS+EGFR联合 → WO/2026/156312 → 联合用药。KRAS抑制剂（MRTX1133）与EGFR抑制剂（奥希替尼）联合，增强KRAS突变结直肠癌治疗效果。希腊国家研究院 → MALT-1抑制剂 → WO/2026/154051 → DPP-4抑制剂（格列汀类）。格列汀类药物作为MALT-1变构抑制剂，用于过敏性炎症、自身免疫病、多发性骨髓瘤和神经胶质瘤。 NeuroDawn Pharma → CSF1R抑制剂 → WO/2026/153352 → 吡啶衍生物。CSF1R抑制活性，广泛用于癌症、自身免疫病、神经退行性疾病等。 Kim, Chul Geun（韩国） → MBD2-p66α相互作用抑制剂 → WO/2026/155426 → 小分子。抑制MBD2-p66α（GATAD2A）相互作用，抑制癌症转移。南部大学（韩国） → 款冬花提取物Tussilagone → WO/2026/155390 → 天然产物。款冬花提取物款冬酮，p38 MAPK通路调节剂，用于肝细胞癌。 Magallanes大学（智利） → 多糖 → WO/2026/152242 → 天然产物。具有抗氧化活性、多种癌细胞细胞毒活性和愈合活性的多糖。二、心血管领域（3项）江苏恒瑞医药 → 心肌肌球蛋白抑制剂 → WO/2026/153470 → 小分子。用于非梗阻性肥厚型心肌病，与Mavacamten和Aficamten相比稳态时间更短、安全性更高。江苏恒瑞医药 → 取代苯丙酸衍生物制备(Lp(a)抑制剂) → WO/2026/153506 → 工艺方法。使用烯烃还原来制备取代苯丙酸衍生物的工艺专利。三、神经系统领域（8项）深圳信立泰药业 → 氘代右美沙芬+安非他酮 → WO/2026/153457 → 复方双层片制剂。氘代右美沙芬速释层+安非他酮缓释层复方制剂。深圳翰宇生物医药 → 线粒体功能改善 → WO/2026/153500 → 三环化合物。改善线粒体功能，用于线粒体功能障碍相关疾病。 Bioprojet（法国） → 多巴胺D3受体部分激动剂 → WO/2026/154032 → 小分子。用于强迫症或抽动障碍（Gilles de la Tourette综合征）等强迫性重复障碍。波尔多大学 → 亚砜化吩噻嗪 → WO/2026/154091 → 小分子。用于治疗神经病变引起的疼痛感觉。鹿儿岛大学 → Nrf2激活剂 → WO/2026/155265 → 小分子。用于HTLV-1相关脊髓病（HAM）治疗。 Zenara Pharma（印度） → Pitolisant口服液 → WO/2026/154345 → 制剂。组胺H3受体拮抗剂/反向激动剂口服液，用于发作性睡病白天过度嗜睡或猝倒。 Kymera Therapeutics → IRF5降解剂 → WO/2026/156070 → PROTAC。干扰素调节因子5（IRF5）降解剂，通过泛素化调节IRF5蛋白。 I3S（葡萄牙） → 低剂量多巴胺能药物 → WO/2026/155658 → 小分子。低剂量（左旋多巴当量<300mg/天）延缓脊髓小脑共济失调3型和阿尔茨海默病进展。四、代谢/糖尿病领域（5项）歌礼制药（Ascletis） → GLP-1R激动剂晶型 → WO/2026/153543 → 晶型/无定形。GLP-1R激动剂化合物晶型1、晶型2、无定形1和无定形2，用于GLP-1介导相关疾病。 Palefiber, SL（西班牙） → Orforglipron舌下喷雾 → WO/2026/154212 → 制剂。口服GLP-1受体激动剂Orforglipron舌下口腔喷雾剂，用于2型糖尿病。 Morehouse医学院 → 褪黑素受体激动剂 → WO/2026/155953 → 小分子。低血脑屏障穿透性褪黑素受体激动剂，用于夜间光照暴露受试者的代谢、胃肠、心血管疾病。山东省分析测试中心 → 薏苡仁低聚糖（CSO） → WO/2026/152787 → 天然产物。分子量1847 Da，葡萄糖:半乳糖=96.5:3.5，具有降尿酸、降糖和抗炎活性。 Pfizer（辉瑞） → 降钙素/胰淀素受体激动剂 → WO/2026/154417 → 稠合杂环酰胺/磺酰胺。用于肥胖、体重增加和2型糖尿病治疗。 Aconcagua Bio → 降钙素/胰淀素受体调节剂 → WO/2026/156091 → 小分子。降钙素受体和/或胰淀素受体活性调节剂。五、神经退行领域（8项）罗氏（F. Hoffmann-La Roche） → TYK2降解剂 → WO/2026/156128、WO/2026/156133、WO/2026/156134 → PROTAC（三篇连发）。TYK2蛋白降解剂三篇连续公开，通过降解调节TYK2，用于自身免疫病、炎症疾病、增殖性疾病、神经系统疾病等，体现罗氏在PROTAC平台的深度布局。百时美施贵宝（BMS） → RIPK1激酶抑制剂 → WO/2026/155973 → 三唑并吡啶基化合物。激酶调节剂包括RIPK1调节。布雷西亚大学 → Synapsin-III/α-突触核蛋白相互作用调节剂 → WO/2026/154410 → 小分子。结合突触蛋白III，减少其与α-突触核蛋白纤维状聚集体，用于帕金森病、路易体痴呆、多系统萎缩等突触核蛋白病。加州理工学院 → CPE羧肽酶E小分子模拟物 → WO/2026/156335 → 小分子。选择性结合5-HTR1E受体，触发β-arrestin募集、ERK磷酸化和BCL-2上调，具有神经保护作用。九州大学 → 蛋白硝化抑制剂 → WO/2026/155157 → 甘油前药。含有甘油或其前药的蛋白硝化抑制剂，用于预防或治疗蛋白硝化引起的疾病。 Exciva GmbH → Deramciclane+右美沙芬 → WO/2026/156036 → 联合用药。Deramciclane与右美沙芬联合提高治疗血浆浓度。六、抗炎止痛领域（7项）海思科医药集团 → Nav1.8抑制剂 → WO/2026/153347 → 含磷磺酰胺衍生物。用于Nav1.8相关疼痛疾病。明慧医药（杭州） → JAK抑制剂晶型/中间体 → WO/2026/153364 → 晶型/工艺。JAK抑制剂化合物的制备方法、晶型及中间体，工艺简单、产率高、纯度高。广州正大创新药业 → PDE4抑制剂制剂 → WO/2026/153257 → 制剂。PDE4抑制剂组合物及制剂，用于呼吸系统疾病。礼来（Eli Lilly） → α4β7整合素抑制剂 → WO/2026/156089 → 小分子。用于炎症性肠病（IBD）、溃疡性结肠炎（UC）和克罗恩病（CD）。 Mother's Pharmaceutical（韩国） → TrkA变构抑制剂 → WO/2026/155575 → 小分子。新型变构TrkA抑制剂，选择性结合TrkA，阻断NGF信号传导并抑制TRPV1活性，用于疼痛障碍或炎症疾病。 Kronolife（泰国） → 天然衰老清除剂 → WO/2026/155701 → 天然产物组合物。原花青素组核心衰老清除剂+细胞增敏剂+抗炎和SASP抑制剂三组植物来源活性成分协同作用。七、免疫领域（1项） Arigenx Therapeutics → AhR激动剂 → WO/2026/153230 → 芳香烃受体激动剂化合物。具有优异的AhR激动活性。 Insmed Incorporated → DPP1抑制剂 → WO/2026/156112 → 小分子。二肽基肽酶1抑制剂化合物及其立体异构体或氘代形式。 —— 数据来源：WIPO PATENTSCOPE数据库，公开日期2026年7月23日（W30周）

2026-07-21

·BioSpace

Atossa Therapeutics Announces Presentation of Mechanism-Driven (Z)-Endoxifen Data in McCune-Albright Syndrome at AACR Special Conference on Rare Cancers

Preclinical Data Poster Highlights Dual Estrogen Receptor and PKC-β/AKT Pathway Modulation as a Potential Therapeutic Strategy for Estrogen-Driven Pathology in McCune-Albright syndrome SEATTLE , July 21, 2026 /PRNewswire/ -- Atossa Therapeutics, Inc. (NASDAQ: ATOS) ("Atossa" or the "Company"), a clinical-stage biopharmaceutical company developing novel therapies in oncology and other areas of significant unmet clinical need, today announced that a poster presentation titled "Dual estrogen receptor and PKC-β signaling modulation by (Z)-Endoxifen: A mechanism-driven therapeutic strategy for estrogen-driven pathology in McCune-Albright Syndrome" was presented at the AACR Special Conference in Cancer Research: Breaking Barriers in the Fight Against Rare Cancers, which took place July 18-20, 2026, in Vancouver, BC, Canada. Presentation Details Session Type: Poster Session A ezstandalone.cmd.push(function () { ezstandalone.showAds(131); }); Date: Saturday, July 18, 2026, 7:30-9:30 pm PT Abstract Number: A010 Location: AACR Special Conference in Cancer Research: Breaking Barriers in the Fight Against Rare Cancers, Vancouver, BC, Canada Poster Title: Dual estrogen receptor and PKC-β signaling modulation by (Z)-Endoxifen: A mechanism-driven therapeutic strategy for estrogen-driven pathology in McCune-Albright Syndrome Presenter: Sandra Hammer, PhD, Atossa Therapeutics Inc. Summary: The poster supports a dual mechanism of action for (Z)-endoxifen in estrogen-driven pathology relevant to McCune Albright Syndrome-associated Peripheral Precocious Puberty (MAS-PPP): the blockade of ER-mediated transcription downstream of autonomous estrogen production and suppression of PKC-β/AKT-associated proliferative and cell-cycle signaling. This multi-pathway pro address a key therapeutic gap in MAS-PPP, where estrogen suppression alone may not fully mitigate downstream proliferative signaling. These findings support further evaluation of (Z)-endoxifen as a targeted therapeutic strategy for MAS-PPP and illustrate how transcriptomic and kinase-network integration can enable therapeutic repositioning for rare endocrine-driven diseases with limited dedicated drug development. They also highlight the potential relevance of (Z)-endoxifen to estrogen-driven neoplasms. Key Highlights McCune-Albright Syndrome (MAS) is a rare mosaic disorder driven by activating GNAS mutations that can result in autonomous estrogen production and chronic estrogen receptor activation. Activating GNAS alterations are recognized oncogenic drivers in multiple neoplasms, positioning MAS a genetically defined model of chronic proliferative signaling that is highly relevant to rare tumor biology. The poster evaluates (Z)-endoxifen, the active metabolite of tamoxifen, as a mechanism-driven strategy to modulate both estrogen receptor signaling and non-ER proliferative kinase pathways relevant to estrogen-driven MAS symptomatology, peripheral precocious puberty. The analysis used weighted gene expression signatures in ER-positive MCF7 cells and integrated published phosphoproteomic and RNA-seq datasets to assess modulation of PKC-β and AKT signaling pathways. The analysis identified a shared estrogen-responsive gene network and showed that (Z)-endoxifen markedly downregulated cell-cycle progression programs, including G2M Checkpoint and E2F Targets, while concurrently modulating estrogen-response pathways. Integration of published mechanistic data further demonstrated that (Z)-endoxifen targets PKC-β1, promotes its dephosphorylation and degradation, and inhibits PMA-induced PKC-β1 and AKT phosphorylation. "MAS related PPP remains a rare and underserved condition where current approaches focus primarily on reducing estrogen production but may not fully address downstream ER-dependent and proliferative signaling," said Dr. Steven C. Quay, M.D., Ph.D., President and Chief Executive Officer of Atossa Therapeutics. "These data support the potential of (Z)-endoxifen as a differentiated, mechanism-driven candidate that may simultaneously modulate estrogen receptor biology and PKC-β /AKT-associated cell-cycle signaling. This finding has direct relevance to several tumor types." About McCune-Albright Syndrome MAS is an extremely rare genetic disorder caused by activating mutations in the GNAS gene, leading to mosaic endocrine dysregulation. Because it is so rare and has a broad spectrum of symptoms, diagnosis can be challenging. The disease is characterized by a triad of symptoms: Polyostotic Fibrous Dysplasia : replacement of normal bone with weak, fibrous tissue, leading to fractures, deformities, and pain; Café-au-lait Spots : hyperpigmented skin patches with irregular, "jagged" borders that typically respect the body's midline; and Hyperfunctioning Endocrinopathies : commonly known as precocious puberty, where children (especially girls) may begin puberty as early as age two. In pediatric patients, MAS commonly presents with gonadotropin-independent precocious puberty, particularly in females, which can result in accelerated growth, premature epiphyseal closure, and reduced adult height. Additional complications may include thyroid dysfunction, growth hormone excess, and other endocrine abnormalities. There are currently limited effective treatment options, highlighting the need for new therapeutic approaches. About Atossa Therapeutics Atossa Therapeutics, Inc. (Nasdaq: ATOS) is a clinical-stage biopharmaceutical company developing innovative medicines in oncology and other areas of significant unmet need. The Company's lead product candidate, (Z)-endoxifen, is currently in development across several clinical settings. (Z)-endoxifen is a potent Selective Estrogen Receptor Modulator/Degrader (SERM/D) with demonstrated activity across multiple mechanisms of interest. Atossa is evaluating its potential applications in oncology and rare diseases. The Company's proprietary oral formulation has shown a favorable safety pro pharmacology distinct from tamoxifen, including ER-targeted effects and PKC inhibition. Atossa's (Z)-endoxifen is not approved for any indication. Atossa's (Z)-endoxifen program is supported by a growing global intellectual property portfolio, including multiple recently issued U.S. patents and numerous pending applications worldwide. More information is available at . Forward-Looking Statements This press release contains certain "forward-looking statements" within the meaning of applicable securities laws, including, but not limited to, our expectations regarding the Company's development and regulatory strategy and related milestones, including the potential indications that the Company may pursue for (Z)-endoxifen, the potential role of (Z)-endoxifen in endocrine therapies, the potential for (Z)-endoxifen to receive regulatory approval and the timing thereof, expectations regarding the design, enrollment, data, timing, results and outcomes of the Company's clinical studies, the potential clinical significance of preclinical data, and the potential market and growth opportunities for the Company. Words such as "expect," "potential," "continue," "may," "will," "should," "could," "would," "seek," "intend," "plan," "estimate," "anticipate," "believe," "design," "predict," "future," or other similar expressions or statements regarding intent, belief or current expectations, are forward-looking statements. Forward-looking statements in this press release are subject to risks and uncertainties that may cause actual results, outcomes, or the timing of actual results or outcomes to differ materially from those projected or anticipated, including, without limitation, risks and uncertainties associated with: our ability to successfully execute our strategy to shorten our clinical development timelines for our lead program, (Z)-endoxifen; expected timing, completion and results of our preclinical studies, clinical trials, and research and development programs; the unpredictable relationship between preclinical study results and clinical study results; the timing or likelihood of regulatory filings and approvals; the outcome or timing of necessary regulatory approvals; our ability to maintain compliance with Nasdaq listing requirements; our ability to establish and maintain intellectual property rights covering our products; the impact of general macroeconomic conditions on our business; our ability to raise capital; and other risks and uncertainties detailed from time to time in Atossa's filings with the SEC, including, without limitation, its Annual Reports on Form 10-K and Quarterly Reports on Form 10-Q. Forward-looking statements are presented as of the date of this press release. Except as required by law, we do not intend to update any forward-looking statements. View original content to download multimedia: SOURCE Atossa Therapeutics Inc

100 项与内昔芬相关的药物交易

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研发状态

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适应症	最高研发状态	国家/地区	公司	日期
躁狂	临床3期	美国	Jina Pharmaceuticals, Inc.	2024-03-19
躁郁症1型	临床3期	美国	Jina Pharmaceuticals, Inc.	2020-08-03
ER阳性乳腺癌	临床2期	美国	Inclin, Inc.	2023-02-14
ER阳性乳腺癌	临床2期	美国	Atossa Therapeutics, Inc.	2023-02-14
GRPR阳性/ER阳性/HER2阴性乳腺癌	临床2期	美国	Inclin, Inc.	2023-02-14
GRPR阳性/ER阳性/HER2阴性乳腺癌	临床2期	美国	Atossa Therapeutics, Inc.	2023-02-14
HER2 阴性乳腺癌	临床2期	美国	Atossa Therapeutics, Inc.	2023-02-14
HER2 阴性乳腺癌	临床2期	美国	Inclin, Inc.	2023-02-14
浸润性乳腺癌	临床2期	美国	Atossa Therapeutics, Inc.	2023-02-14
浸润性乳腺癌	临床2期	美国	Inclin, Inc.	2023-02-14

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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


NCT05607004 (EVANGELINE, SABCS2025) 人工标引	临床2期	ER阳性/HER2阴性乳腺癌新辅助 Estrogen receptor positive \| HER2 Negative	22	(Z)-endoxifen (40mg vs 80mg) ± Goserelin (Part 1 (PK Run-in))	壓簾繭膚鑰壓繭糧構願(憲獵襯鏇壓齋鹽繭範憲) = 膚醖構獵積膚製構糧選蓋築築獵獵繭艱醖齋鑰 (鹽選鑰蓋選鹹積窪鑰構 )	积极	2025-12-09
NCT05068388 (KARISMA-Endoxifen, Company_Website) 人工标引	临床2期	乳腺癌	-	(Z)-endoxifen 1 mg	觸網繭壓顧餘衊膚膚願(繭鹽齋獵鏇壓顧獵蓋獵) = 蓋獵鬱餘網醖構願簾糧醖廠範範簾蓋鹽網蓋獵 (艱鹽齋糧齋鑰範遞淵衊 ) 更多	积极	2024-11-04
				(Z)-endoxifen 2 mg	觸網繭壓顧餘衊膚膚願(繭鹽齋獵鏇壓顧獵蓋獵) = 獵願廠構製積艱襯鏇遞醖廠範範簾蓋鹽網蓋獵 (艱鹽齋糧齋鑰範遞淵衊 ) 更多
NCT05607004 (EVANGELINE, AACR2024) 人工标引	临床2期	绝经前乳腺癌新辅助 HER2 Negative \| Proliferation marker protein Ki-67 \| ER Positive	7	(Z)-endoxifen 40 mg/day	膚廠憲齋夢齋築鬱艱顧(繭憲獵鏇獵選膚顧鏇鏇) = 膚醖願憲醖夢顧艱繭鹽築艱夢鏇醖廠觸餘積遞 (製糧壓蓋壓鬱築鏇淵艱, 180.3 ~ 376.6) 更多	积极	2024-04-05
NCT03317405 (CTgov)	临床1期	乳腺导管癌 \| 乳腺原位癌	32	Endoxifen Hydrochloride (Endoxifen Hydrochloride Gel 10 mg Daily)	構糧鏇餘齋廠獵網憲餘 = 積簾憲鹹壓窪製願築鹽範憲簾範壓憲鬱鹹鏇齋 (築範蓋醖襯壓範鏇襯製, 襯網鹽鏇遞糧網蓋獵餘 ~ 鹹鬱憲鹽餘製鹹獵鏇鑰) 更多	-	2023-06-13
				Endoxifen Hydrochloride (Endoxifen Hydrochloride Gel 20 mg Daily)	構糧鏇餘齋廠獵網憲餘 = 築網遞衊襯範願鏇選鬱範憲簾範壓憲鬱鹹鏇齋 (築範蓋醖襯壓範鏇襯製, 餘艱壓鬱壓鏇獵願製壓 ~ 淵鬱構網齋廠觸膚鑰衊) 更多
NCT02311933 (PD7-06, CTgov)	临床2期	复发性乳腺癌 \| 局部晚期乳腺癌 \| 转移性乳腺癌 ... 更多	81	Pharmacological Study+Endoxifen Hydrochloride (Arm I (Z-endoxifen Hydrochloride))	簾夢夢築簾觸網鹹遞顧(糧艱淵夢艱鑰夢獵繭積) = 餘艱襯醖繭齋襯醖齋遞蓋範顧廠選積廠壓廠獵 (衊衊製蓋簾糧淵糧網餘, 製鏇襯廠繭鹽餘艱築鬱 ~ 襯遞簾壓餘艱鑰鑰網襯) 更多	-	2021-09-28
				Pharmacological Study+Tamoxifen Citrate (Arm II (Tamoxifen Citrate))	簾夢夢築簾觸網鹹遞顧(糧艱淵夢艱鑰夢獵繭積) = 襯艱鹹鹽膚廠觸鑰鹽鏇蓋範顧廠選積廠壓廠獵 (衊衊製蓋簾糧淵糧網餘, 簾觸膚蓋憲積鑰網繭願 ~ 廠積觸積齋膚製繭鹹選) 更多
NCT04616430 (CREME, CTgov)	临床2期	乳腺疾病	90	Placebo (Control)	簾顧衊網鏇餘獵糧鹽選(簾顧蓋廠糧艱顧餘餘壓) = 淵鬱餘鏇鏇衊淵製製廠鏇襯廠鏇齋糧繭網餘壓 (遞選糧衊糧顧遞齋積糧, 5.58) 更多	-	2021-06-18
				Topical endoxifen (Topical Endoxifen 10mg/Breast/Day)	簾顧衊網鏇餘獵糧鹽選(簾顧蓋廠糧艱顧餘餘壓) = 鏇艱構選壓鑰積廠窪齋鏇襯廠鏇齋糧繭網餘壓 (遞選糧衊糧顧遞齋積糧, 6.50) 更多
NCT02311933 (AACR2020) 人工标引	临床2期	HER2 阴性乳腺癌 \| ER阳性乳腺癌 HER2 negative \| ER Positive	77	Z-endoxifen HCL	壓衊醖簾築鑰衊鑰鏇積(鹹鬱遞製餘鏇簾遞齋鏇) = 廠鏇繭鹽積壓鑰鏇廠鹹鹹憲壓獵齋憲鹹糧簾築 (壓網壓鏇簾鏇鹽憲製齋, 76 ~ 138)	非优	2020-02-15
				tamoxifen	壓衊醖簾築鑰衊鑰鏇積(鹹鬱遞製餘鏇簾遞齋鏇) = 憲淵餘壓鬱鏇淵憲鏇餘鹹憲壓獵齋憲鹹糧簾築 (壓網壓鏇簾鏇鹽憲製齋, 24 ~ 129)
NCT01273168 (ASCO 12018 \| ASCO 22018) 人工标引	临床1期	HR阳性实体瘤 HR Positive	40	Endoxifen	網願網範積獵構範簾齋(築窪網醖蓋獵鬱蓋網鏇) = hypertension (13%), hyponatremia (8%), hypophosphatemia (8%), neutropenia (8%), dehydration (5%), and elevated ALT (5%) 蓋襯鑰鹽網餘艱蓋襯鏇 (壓顧淵鏇顧鬱襯顧繭蓋 ) 更多	积极	2018-06-04
NCT01327781 (MC093C, ASCO2017)	临床1期	激素难治性乳腺癌	41	Z-endoxifen	鹽壓範糧顧鬱鑰醖夢糧(築鏇窪餘膚夢網鬱遞獵) = 餘蓋夢網夢構窪鹹鬱製艱範鏇餘鏇願膚顧範鹹 (願獵鑰淵憲襯觸鏇鹽願, 13.4 ~ 43.1) 更多	-	2017-05-30
NCT01327781 (phase I study of Z-Endoxifen hydrochloride, SABCS2016)	临床1期	转移性乳腺癌 ER+	41	Z-Endoxifen hydrochloride (Z-Endx)	築醖鑰製願觸繭鏇憲築(鹹餘膚艱窪襯淵鏇餘觸) = 餘淵觸淵簾鏇範鏇醖憲積觸窪廠艱蓋範齋憲夢 (願簾繭築繭膚製願廠衊 )	积极	2016-02-15