更新于：2024-11-01

Ethisterone

炔孕酮

更新于：2024-11-01

概要

概要

基本信息

药物类型

小分子化药

别名

ethisterone

靶点-

作用机制-

治疗领域

神经系统疾病泌尿生殖系统疾病其他疾病

在研适应症

闭经痛经子宫出血

非在研适应症-

原研机构

秦皇岛紫竹药业有限公司

在研机构

秦皇岛紫竹药业有限公司

非在研机构-

最高研发阶段批准上市

首次获批日期-

最高研发阶段(中国)批准上市

特殊审评-

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结构

分子式C21H28O2

InChIKeyCHNXZKVNWQUJIB-CEGNMAFCSA-N

CAS号434-03-7

关联

100 项与炔孕酮相关的临床结果

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100 项与炔孕酮相关的转化医学

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100 项与炔孕酮相关的专利（医药）

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115

项与炔孕酮相关的文献（医药）

2024-01-01·PROTEOMICS – Clinical Applications

LC‐MS‐based urine metabolomics analysis of chronic subdural hematoma for biomarker discovery

Article

作者: Qi, Feng ; Sun, Jiameng ; Liu, Xiaoyan ; Lan, Ying ; Liu, Weiming ; Ou, Yunwei ; Sun, Wei ; Guo, Zhengguang ; Sun, Haidan

AbstractBackgroundChronic subdural hematoma (CSDH) is one of the most common neurosurgical diseases with atypical manifestations. The aim of this study was to utilize urine metabolomics to explore potential biomarkers for the diagnosis and prognosis of CSDH.MethodsSeventy‐seven healthy controls and ninety‐two patients with CSDH were enrolled in our study. In total, 261 urine samples divided into the discovery group and validation group were analyzed by LC‐MS. The statistical analysis and functional annotation were applied to discover potential biomarker panels and altered metabolic pathways.ResultsA total of 53 differential metabolites were identified in this study. And the urinary metabolic profiles showed apparent separation between patients and controls. Further functional annotation showed that the differential metabolites were associated with lipid metabolism, fatty acid metabolism, amino acid metabolism, biotin metabolism, steroid hormone biosynthesis, and pentose and glucuronate interconversions. Moreover, one panel of Capryloylglycine, cis‐5‐Octenoic acid, Ethisterone, and 5,6‐DiHETE showed good predictive performance in the diagnosis of CSDH, with an AUC of 0.89 in discovery group and an AUC of 0.822 in validation group. Another five metabolites (Trilobinol, 3′‐Hydroxyropivacaine, Ethisterone, Arginyl‐Proline, 5‐alpha‐Dihydrotestosterone glucuronide) showed the levels of them returned to a healthy state after surgery, showing good possibility to monitor the recovery of CSDH patients.Conclusion and Clinical RelevanceThe findings of the study revealed urine metabolomic differences between CSDH and controls. The potentially diagnostic and prognostic biomarker panels of urine metabolites were established, and functional analysis demonstrated deeper metabolic disorders of CSDH, which might conduce to improve early diagnose of CSDH clinically.

2023-10-02·Molecular cancer therapeutics

A Multivalent Peptoid Conjugate Modulates Androgen Receptor Transcriptional Activity to Inhibit Therapy-resistant Prostate Cancer.

Article

作者: Wong, Kwok-Kin ; Wise, David R ; Ayasun, Ruveyda ; Zoubeidi, Amina ; Pereira, Luiza D ; Ranieri, Michela ; Ruoff, Rachel ; Ha, Susan ; Deng, Jiehui ; Kasper, Amanda C ; Habault, Justine ; Claessens, Frank ; Bar-Sagi, Dafna ; Schneider, Jeffrey A ; Kirshenbaum, Kent ; Garabedian, Michael J ; Logan, Susan K ; Puccini, Joseph

Prostate cancers adapt to androgen receptor (AR) pathway inhibitors and progress to castration resistance due to ongoing AR expression and function. To counter this, we developed a new approach to modulate the AR and inhibit castration-resistant prostate cancer (CRPC) using multivalent peptoid conjugates (MPC) that contain multiple copies of the AR-targeting ligand ethisterone attached to a peptidomimetic scaffold. Here, we investigated the antitumor effects of compound MPC309, a trivalent display of ethisterone conjugated to a peptoid oligomer backbone that binds to the AR with nanomolar affinity. MPC309 exhibited potent antiproliferative effects on various enzalutamide-resistant prostate cancer models, including those with AR splice variants, ligand-binding mutations, and noncanonical AR gene expression programs, as well as mouse prostate organoids harboring defined genetic alterations that mimic lethal human prostate cancer subtypes. MPC309 is taken up by cells through macropinocytosis, an endocytic process more prevalent in cancer cells than in normal ones, thus providing an opportunity to target tumors selectively. MPC309 triggers a distinct AR transcriptome compared with DHT and enzalutamide, a clinically used antiandrogen. Specifically, MPC309 enhances the expression of differentiation genes while reducing the expression of genes needed for cell division and metabolism. Mechanistically, MPC309 increases AR chromatin occupancy and alters AR interactions with coregulatory proteins in a pattern distinct from DHT. In xenograft studies, MPC309 produced significantly greater tumor suppression than enzalutamide. Altogether, MPC309 represents a promising new AR modulator that can combat resistant disease by promoting an AR antiproliferative gene expression program.

2023-01-01·Frontiers in plant science

Metabolomics reveals the response of hydroprimed maize to mitigate the impact of soil salinization.

Article

作者: Zhang, Enying ; Tian, Xiaomin ; Wei, Yueheng ; O'Connor, David ; Wang, Wenli ; Mou, Xinshang ; Sun, Yue ; Zhu, Xingjian ; Ravenscroft, Neil ; Zhang, Yanli ; Fang, Zhixuan ; Chang, Xianmin ; Yan, Min ; Chen, Ziyi

Soil salinization is a major environmental stressor hindering global crop production. Hydropriming has emerged as a promising approach to reduce salt stress and enhance crop yields on salinized land. However, a better mechanisitic understanding is required to improve salt stress tolerance. We used a biochemical and metabolomics approach to study the effect of salt stress of hydroprimed maize to identify the types and variation of differentially accumulated metabolites. Here we show that hydropriming significantly increased catalase (CAT) activity, soluble sugar and proline content, decreased superoxide dismutase (SOD) activity and peroxide (H₂O₂) content. Conversely, hydropriming had no significant effect on POD activity, soluble protein and MDA content under salt stress. The Metabolite analysis indicated that salt stress significantly increased the content of 1278 metabolites and decreased the content of 1044 metabolites. Ethisterone (progesterone) was the most important metabolite produced in the roots of unprimed samples in response to salt s tress. Pathway enrichment analysis indicated that flavone and flavonol biosynthesis, which relate to scavenging reactive oxygen species (ROS), was the most significant metabolic pathway related to salt stress. Hydropriming significantly increased the content of 873 metabolites and significantly decreased the content of 1313 metabolites. 5-Methyltetrahydrofolate, a methyl donor for methionine, was the most important metabolite produced in the roots of hydroprimed samples in response to salt stress. Plant growth regulator, such as melatonin, gibberellin A8, estrone, abscisic acid and brassinolide involved in both treatment. Our results not only verify the roles of key metabolites in resisting salt stress, but also further evidence that flavone and flavonol biosynthesis and plant growth regulator relate to salt tolerance.

项与炔孕酮相关的新闻（医药）

2024-10-26

·凯莱英药闻

瞄准全球1.9亿女性！和其瑞医药“全球首创”PRLR单抗公布2期临床最新进展

近日，和其瑞医药宣布，公司针对HMI-115在中度至重度子宫内膜异位症相关疼痛女性患者中，开展的一项2 期研究中期分析结果积极。HMI-115是一款靶向泌乳素受体（PRLR）的单克隆抗体，具有全球首创的治疗机制；公司计划快速推进全球 3 期试验，以便患者能够尽快开始从 HMI-115 治疗中受益。该2期研究是一项国际多中心、随机、双盲、安慰剂对照试验，用于评估HMI-115 在12 周治疗期内对中度至重度子宫内膜异位症相关疼痛女性的安全性和有效性。该研究在142 名包括美国、波兰和中国的女性患者中开展，中期研究显示：与基线相比，240 mg q2w 组的平均痛经疼痛评分降低了 42%；平均非月经期盆腔疼痛评分降低了 50%。大多数患者报告月经正常。没有报告典型的围绝经期症状。骨矿物质密度和性激素水平（包括雌二醇、LH、FSH 和孕酮）没有显著变化。 HMI-115以非竞争性方式阻断 PRLR介导的信号传导，获得中国国家药品监督管理局 (NMPA) 的突破性疗法认定，用于治疗子宫内膜异位症相关的中重度疼痛。该最早由拜耳开发，和其瑞医药与其签署了一项全球独家许可协议，在全球范围内针对HMI-115（BAY 1158061）进行多个适应症的开发和产业化。除子宫内膜异位症适应症外，公司已完成一项Ib 期研究，旨在评估HMI-115 治疗雄激素性脱发患者的安全性、耐受性和疗效，研究显示：2 名男性患者的平均非毫毛靶区毛发数 (TAHC) 与基线相比增加了 14 根/cm2，药物安全且耐受性良好。 PRLR是1型细胞因子/造血功能受体超家族的一员，在免疫系统中广泛表达，包括单核细胞、淋巴细胞、巨噬细胞、NK细胞、粒细胞和胸腺上皮细胞。研究表明，PRL与自身免疫性疾病、乳腺癌、前列腺癌、卵巢癌、胰腺癌和子宫内膜癌等疾病相关。 PRLR结合配体时，发生构象变化，并激活下游多条信号通路，包括Jak2/Stat5和Jak1/Stat3通路，以及通过Src家族激酶和粘着斑激酶（FAK）的激活，有助于在癌细胞系中诱导PI3K/Akt和Raf/MEK/ERK的激活。据不完全统计，目前在研的PRLR药物不足十种。内异症是生育年龄女性的多发病、常见病，具有性激素依赖的特点。内异症的临床表现多样，其中最为重要和影响巨大的是疼痛（常与经期相关）和不孕。内异症严重影响患者的生理、心理、性爱、交际、生育，并带来沉重的家庭、社会经济及国家发展负担。据统计，全球约有 1.9 亿女性患有子宫内膜异位症，市场规模约为 2000 亿美元。现有的内异症的治疗手段主要包括手术和药物，均不能从根本上为患者提供有效安全且可长期使用的治疗手段。手术治疗可切除肉眼可见的病变，但因疾病本身发病机制不明朗，术后复发率居高不下（术后复发率每年增10%，术后5年累积复发率为 50%），且手术容易引发肠道、泌尿道和血管并发症。当前各种治疗药物（常用药物：非甾体抗炎药类、复方口服避孕药、孕激素类、GnRH激动剂）存在各自缺陷，患者可能因疗效不佳或者不能耐受副作用等情况而停止治疗，使得病情失去监控，再次反复。和其瑞医药是一家科学驱动的临床阶段创新生物制药公司，基于北京大学未来技术学院院长肖瑞平教授及其团队在转化医学研究领域的深入理解及数十年的研究成果。公司针对威胁人类健康的常见病和重大疾病，致力于研究、开发和商业化首创新药。参考资料 1、公司官网内容来源于网络，如有侵权，请联系删除。