A Phase II Study of Sequential Bipolar Androgen Therapy and ZEN-3694 in Sequence With Enzalutamide + ZEN-3694 in Asymptomatic Patients With Metastatic CRPC: The COSMYC Trial (COmbined Suppression of MYC)

This research is being done to determine if receiving the combination of testosterone and ZEN-3694 followed by the combination of enzalutamide plus ZEN-3694 will decrease the size of tumors in patients with prostate cancer that has become resistant to castration and other therapies. The investigators also want to determine if dosing first with the combination of testosterone and ZEN-3694 may cause enzalutamide and ZEN-3694 to work more effectively.

开始日期2025-08-30

申办/合作机构

The Sidney Kimmel Comprehensive Cancer Center

[+2]

NCT06450405

/ Terminated临床4期IIT

Androgen Effects on the Reproductive Neuroendocrine Axis

This research study investigates whether male-level exogenous androgens inhibit the reproductive neuroendocrine axis in otherwise healthy (non-PCOS) females.

开始日期2025-02-26

申办/合作机构

University of California San Diego

[+2]

NCT06111209

/ Recruiting临床2期IIT

A Pilot Study to Evaluate the Anabolic Effect of Testosterone on Muscles of the Pelvic Floor in Older Women With Stress Urinary Incontinence

Stress urinary incontinence is the most common female pelvic floor disorder encountered in clinical practice with significant negative impact on quality of life. The prevalence of urinary incontinence increases with aging, and weakness of the pelvic floor muscles contributes to the development of stress urinary incontinence. Given that androgen receptors are expressed throughout the pelvic floor, the anabolic effects of androgens on pelvic floor muscles may provide a therapeutic option in women with stress urinary incontinence. The investigators are conducting a randomized, double-blind, placebo-controlled proof-of-concept trial in older postmenopausal women with stress urinary incontinence to assess whether testosterone therapy can increase pelvic floor muscles and improve urinary function.

开始日期2025-02-15

申办/合作机构

The Brigham & Women's Hospital, Inc.

[+1]

100 项与环戊酸睾酮相关的临床结果

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100 项与环戊酸睾酮相关的转化医学

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100 项与环戊酸睾酮相关的专利（医药）

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646

项与环戊酸睾酮相关的文献（医药）

2025-12-31·JOURNAL OF DERMATOLOGICAL TREATMENT

The impact of cannabis use on local anesthetic dosing during hair restoration surgery: a case report, proposed mechanisms, and clinical recommendations

Review

作者: Keene, Sharon A. ; Gupta, Aditya K. ; Talukder, Mesbah

Cannabis use has increased significantly in the last decade. This article presents a case where a patient needed more local anesthetic (LA) than usual to induce effective anesthesia during hair transplant surgery. The reason cannabis users often need more LA is poorly understood. One possibility is that cannabis withdrawal effect makes patients more sensitive to pain and stress. Additionally, vasodilatory property of cannabis may speed up LA clearance from the application site. The interactions of two major cannabinoids, cannabidiol (CBD) and tetrahydrocannabinol (THC), with cannabinoid receptor type 1 (CB1), cannabinoid receptor type 2 (CB2), and transient receptor potential vanilloid 1 (TRPV1) receptors are also complex. Furthermore, CBD and THC function as cytochrome P450 enzyme inhibitors potentially impacting systemic metabolism. When planning to administer LA during hair restoration surgery in cannabis users, clinicians should obtain a detailed history of prior consumption (type of cannabis, frequency, dosage). Preoperative planning should consider the anticipated duration of surgery and calculate the maximum safe LA dose to avoid the risk of toxicity. Also, patients should be carefully monitored for vital signs during surgery. If a patient requires frequent re-injection to remain pain free, the surgeon may need to re-assess the surgical plan to avoid toxicity.

2025-05-01·MOLECULAR NEUROBIOLOGY

A Novel Neuroprotective Derived Peptide of Erythropoietin Improved Cognitive Function in Vascular Dementia Mice

Article

作者: Wu, Shengju ; Ma, Yuanyuan ; Wang, Xin ; Ding, Jing ; Wu, Tingting ; Xu, Tongtong ; Zhou, Zhiyuan ; Yang, Guo-Yuan

The effective therapeutics for vascular dementia are still lacking. Here, we designed a novel derived peptide of erythropoietin-DEPO and evaluated its safety, erythropoiesis effect, and neuroprotective effects in mice of vascular dementia. For evaluating the safety and erythropoiesis, DEPO was injected into naive C57BL6 mice (n = 5) for 4-8 weeks, and venous blood was collected at 1, 2, and 4 weeks after DEPO treatment. Neuroprotective effects of DEPO were studied in both cultured neurons and bilateral common carotid artery stenosis (BCAS) mice (n = 10/group). After 4-week DEPO administration, neurobehavioral tests and histology were applied to evaluate cognitive function and brain tissue damage of mice, respectively. Molecule docking, western blotting, pharmacological or genetic interference with EPOR, and JAK/STAT/AKT pathway were used to determine the mechanism of neuroprotective effects of DEPO. DEPO did not increase the hemoglobin concentration or red blood cell number in mice after 4-week treatment compared to the Vehicle group (p > 0.05). DEPO treatment alleviated spatial reference memory impairment and the anxiety level in mice (p < 0.05). Both gray and white matter injuries were significantly alleviated by DEPO treatment. DEPO activated JAK/STAT pathway in cultured neurons and protected neurons against chronic ischemia (p < 0.05). Pharmacological or genetic interference with JAK2 signaling or EPOR inhibited the pro-survival effect of DEPO on chronic ischemia neurons (p < 0.05). DEPO is a novel safe erythropoietin-derived peptide and exerted its neuroprotective effects in vascular dementia mice through activating EPOR and its downstream JAK/STAT signaling pathway. DEPO is a potential alternative agent for treatment of vascular dementia or chronic cerebral ischemia.

2025-04-01·European Urology Focus

Reprogramming of Androgen Receptor Activity in Castration-resistant Prostate Cancer is Shaped by Truncated Variants

Article

作者: Taylor, Renea A ; Selth, Luke A ; Teng, Linda ; Lawrence, Mitchell G ; Tilley, Wayne D ; Cuffe, Georgia B ; Hanson, Adrienne R ; Laven-Law, Geraldine ; Choo, Nicholas ; Hickey, Theresa E ; Shrestha, Raj K ; Nelson, Peter S ; Joshua, Anthony M ; Dehm, Scott M ; Knutson, Todd P ; Crumbaker, Megan ; Keerthikumar, Shivakumar ; Risbridger, Gail P ; Clark, Ashlee K ; Corey, Eva ; Townley, Scott L ; Richards, Michelle G

BACKGROUND AND OBJECTIVE:

Under the selective pressure of treatment, prostate cancer cells express constitutively active androgen receptor (AR) variants. Whether AR variants mediate therapy resistance remains contested, because they are often coexpressed with abundant full-length AR. Therefore, we sought to determine how truncated variants shape AR chromatin occupancy and responses to treatments in both the presence and absence of full-length AR.

METHODS:

We used a cohort of patient-derived xenografts of metastatic prostate cancer with diverse AR alterations. Chromatin immunoprecipitation and RNA sequencing were used to compare the landscape of AR binding and transcriptomic features. We assessed responses to castration by castrating host mice and evaluated responses to bipolar androgen therapy by administering testosterone cypionate.

KEY FINDINGS AND LIMITATIONS:

By profiling the AR cistrome, we identified a distinct group of tumours defined by ARv567es expression, a variant arising due to structural rearrangements of the AR gene. ARv567es-positive tumours also had a distinct epigenomic profile and altered transcriptional features, including loss of canonical AR-regulated gene signatures and elevated expression of AR-repressed genes. ARv567es-positive tumours were resistant to castration and bipolar androgen therapy. In tumours that coexpress full-length AR, this involves dampened transcriptional responses and disruption of the autoregulatory loop that modulates AR levels. Study limitations include the need for additional models of AR-driven prostate cancer.

CONCLUSIONS AND CLINICAL IMPLICATIONS:

The emergence of ARv567es via gene rearrangements causes transcriptional reprogramming and therapy resistance. This highlights ARv567es as a potential as a marker to guide treatment decisions.

项与环戊酸睾酮相关的新闻（医药）

2025-05-26

·漫游药化

马大为课题组有关乌尔曼反应的研究进展

小提示：正文字数7882，预计阅读需25分钟题记上海有机化学研究所马大为课题组发展了促进Ullmann反应的氨基酸和草酰二胺两代配体，突破了反应条件苛刻和普适性差的局限，该反应已广泛应用于新药研发和新材料创制，应用超过1500次，其中包括两个临床实验药物的百公斤级生产，以及抗高血压药物培朵普利和治疗干眼病药物Xiidra的吨级生产，700余项美国专利利用这一改进的Ullmann反应设计了合成路线。马大为研究员也因为在这一有机化学领域的卓越贡献，荣获美国化学会2018年Arthur C. Cope学者奖，并被授予2019年度中国科学院杰出科技成就奖。览博网与该课题组合作推出相关乌尔曼反应高效草酰二胺配体，这类配体最显著的特点：（1）突破了此前铜催化的不活泼的芳基氯代物的偶联反应局限；（2）对于较活泼的芳基碘代物和溴代物，可以使得反应在低催化剂量和更为温和的反应条件下进行。下面将简要介绍相关配体的研究进展。背景介绍1901年，F.Ullmann报道了高温下（> 200°C）两当量芳基卤与一当量细铜粉的反应，得到对称的联芳烃和卤化铜。两种芳基卤化物在铜的存在产生对称或不对称的联芳烃，称为乌尔曼反应（乌尔曼联芳烃合成或乌尔曼偶联）。自此发现以来，乌尔曼反应已成为合成众多对称和不对称联芳烃的经典方法。典型的Ullmann反应一般需要剧烈的条件，反应温度高于200℃），过量的Cu粉催化。伴随着金属有机化学的发展，Ullmann反应的适用范围得到了扩展。比如，除了最常用的碘代芳烃，溴代芳烃和氯代芳烃也可用于反应。催化剂除了Cu外，Ni催化的偶联反应也有报道，在药物研发和药物生产过程中经常用到。图1 早期典型的乌尔曼反应马大为课题组有关乌尔曼反应研究进展如上所述，在经典的乌尔曼反应中，反应温度需要达到150℃到250℃，铜催化剂的效率很低，使得这一反应的实用性受到限制。1998年，上海有机所的马大为课题组在合成其他分子过程中，偶然发现了一类氨基酸分子，可以提高乌尔曼反应的效率。接下来发展了一系列基于这个催化体系的反应，他们用了整整10年时间，终于找到了比这类氨基酸分子的催化效率更高的草酰二胺分子。这个新催化体系可以催化更广谱的反应，更有可能用来制备生物活性分子和材料分子，并且可以在新药研发中发挥重要作用。经改良后的乌尔曼反应，在室温到100℃之间即可发生，从而使得一个不怎么好用的“工具”变成了“利器”。如果把催化剂比作一台挖掘机，催化剂中的金属相当于钻头，它的配体就是助推器，可以说马大为课题组找到了乌尔曼反应目前推力最大的助推器，而且钻头用的是很便宜的金属铜。因此可以在医药和材料合成领域得到广泛应用。1. N,N‘-二（2,4,6-三甲氧基苯基）草酰二胺（BTMPO）作为铜催化不活泼的芳基氯化物与烷基胺类偶联反应的最佳配体[1]芳基胺是学术界和工业界最重要的化学品之一。该种基本骨架在具有生物活性的天然产物和药物等人工化合物中非常常见。在现有的制备芳基胺的方法中，（杂）芳基卤化物与胺的金属催化偶联反应变得越来越有吸引力。虽然在过去的二十年中，大量的Pd和Cu基催化体系被开发用于胺的芳基化，但因为胺与过渡金属具有很强的配位亲和力，如何实现高转化率成为化学家们一项严峻的挑战。2015年课题组发现草酸二胺是有效的配体，能够与铜在相对温和的条件下催化活性较低(杂)芳基氯化物的胺化反应。经过筛选多种草酸二胺，发现BTMPO是该反应的最佳配体，最佳的反应条件为：以磷酸钾为碱，在120℃条件下进行，在DMSO中生成多种(杂)芳基胺，大多数产率可达到70%以上。并且大量的官能化(杂)芳基氯化物和胺符合目前的反应条件，从而可以合成具有多种结构特征的(杂)芳基胺。详细催化反应结果如下图所示。此研究的重要意义在于，草酸二胺配体非常便宜、方便、结构可调。这些显著的特点使该方法成为制备(杂)芳基胺的一种很有吸引力的方法。这一发现促进了后面一系列的铜催化的芳基化反应的配体设计。图2 CuI/BTMPO催化(杂)芳基氯化物与胺的偶联反应的范围2. N,N‘-二（2-苯基-4-甲基苯基）草酰二胺（BPMPO）作为铜催化不活泼的芳基氯化物与氨偶联反应的最佳配体[2]初级(杂)芳基胺是有机化学中最重要的原料之一，广泛应用于制药、农药、染料和电子材料的生产。到目前为止，每年生产的初级(杂)芳基胺超过600万吨，最常用的制备方法是先硝化芳烃，然后加氢，由于大量使用过量的混合硝酸和硫酸产生了严重的污染物，已经造成了严重的环境问题。为解决这一问题，马大为课题组在2015年筛选多种草酸二胺，发现BPMPO是该反应的最佳配体，在CuI催化下芳基氯化物与水或气态氨发生偶联反应。反应在105-120℃下进行，生成了一系列不同官能团的初级(杂)芳基胺。大多数产率可达到70%以上。这种方法是现有的从杂芳基氯化物中合成初级(杂)芳基胺的许多方法的有益补充，而且在许多情况下，该反应在成本(催化剂、配体和碱)、底物适用范围和反应条件方面具有明显的优势。详细催化反应结果如下图所示。图3 CuI/BPMPO催化(杂)芳基氯化物与胺的偶联反应的范围3. N-（1-萘基）-N’-烷基类草酰二胺（MNBO）作为铜催化芳基卤化物与胺类反应的最佳配体[3]2017年，马大为课题组筛选了一系列草酸二酰胺配体后，研究证明MNBO可作为有效配体，使芳基溴与伯胺和氨的偶联反应仅用0.1mol%的Cu2O催化剂和配体即可完成，且反应底物适用范围广泛，无论是各类（杂）芳基卤化物（I，Br）还是各种胺类在该条件下均能表现出良好的反应活性。1) MNBO-Cu2O作为最佳反应配体催化（杂）芳基卤化物与伯胺的偶联反应研究者首先进行了以4-溴茴香醚和苄胺为底物，以0.1mol%的Cu2O和0.1mol%的配体催化下发生的偶联反应的探索。最初，使用BTMPO（L1）作为配体，该配体是铜催化芳基氯化物与伯胺偶联的最佳配体。在80°C的叔丁醇中，6h后的转化率仅为1%。通过使用BPMPO（L2）观察到类似的结果，但该配体在铜催化的芳基氯和氨的偶联反应中表现良好（entry2）。因此，初步探索失败后，研究人员选择修改配体来进行反应最佳配体的探索，使用N-芳基-N’-烷基取代的草酰胺（L3）作为配体，反应获得了显著的改善（entry3）。基于L3的进一步的结构-活性关系研究表明，MNBO（L4）的反应结果最好（entry4）。在这种情况下，将反应时间延长到12h底物得到了几乎完全转换（entry5）。将L4中的苄基改为2-呋喃甲基（MNFO，L5）对收率并没有产生影响（entry6）。然而，当L4中的苄基和2-甲基-1-萘基基团被替换成到2-甲基-1-萘基（L6，entry7）和1-萘基（L7，entry8）时，反应产率明显下降。当使用L5的简化类似物L8（NFO）时，也得到了类似的结果（entry9）。此外，将溶剂改为乙醇并不影响转化（entry8）。图4 最佳配体MNBO的探索然后用各种（杂）芳基溴和伯胺对所建立的最佳反应条件进行了探索，几种取代芳基溴已证明可以75-98%的收率转化为最终产物。如下图所示。图5 MNBO作为催化反应配体的底物适用性当底物为更具反应活性的（杂）芳基碘时，发现0.01mol%的Cu2O和MNBO足以催化芳基胺化。在50°C时，乙醇溶液中反应迅速，偶联产物的产率为88-95%。由下图可知，该改进的乌尔曼偶联反应底物使用广泛，反应活性良好，转化充分，且所需催化剂及配体的用量更加经济合理。图6 MNBO配体在活性更高的芳基卤化物底物中的应用2) N-(1-萘基)-N-(2-呋喃甲基)-草二酰胺(MNFO)/NFO作为芳基卤化物与氨偶联的最佳配体研究者进一步探索了该方法在芳基卤化物与氨偶联合成初级芳胺的适用性，在0.1mol%的Cu2O和MNFO（或NFO）催化下，氨水可与富电子或缺电子的芳基卤化物反应产生相应的胺化产物。反应结果如下图所示，所有芳基碘的偶联氨化都是在比相应的溴化物更低的温度下进行。且反应条件温和，普遍产率达到60%以上，可适用的底物广泛。图7 MNFO/NFO作为芳基卤化物与氨偶联配体的底物适用性3) MNBO作为饱和氮杂环与芳基卤化物偶联的最佳配体N-芳基饱和氮杂环骨架在药物发现中具有重要意义。在此背景下，使用的新的催化体系来尝试杂芳基卤化物与饱和氮杂环的偶联反应。发现Cu2O和MNBO的结合对胺偶联底物的空间位阻很敏感，因此需要增加催化浓度才能完全转化。一般来说，0.1~0.5mol%的Cu2O和MNBO能有效地催化（杂）芳基溴与简单饱和氮杂环的偶联。图8 MNBO作为环仲胺与芳基卤化物偶联配体的底物适用性4. N, -双[(2-呋喃基)甲基]草酸酰胺(BFMO) 作为Cu2O催化氮杂环的N-芳基化的高效配体[4] BFMO是一种由廉价的呋喃基胺和草酸氯合成的酰胺。Cu2O与BFMO的结合适用于催化10多种不同类型氮杂环与芳基卤化物发生偶合反应生成N-芳基化产物，这些氮杂环包括吡啶类、吲哚类、吡咯类等，在标准条件下，两种底物在低催化浓度(1-2 mol%的催化剂和配体)下表现良好，偶联产物的收率普遍在85%以上。该反应具有底物范围广、配体制备成本低、操作简单、多克级合成能力强等特点。催化反应结果见下表。图9 Cu2O催化4-溴茴香醚与吲哚在不同配体作用下的偶联反应图10 Cu2O/ BFMO催化的(杂)芳基溴代物与氮杂环的偶联反应5. N,N’ -双[(2-噻吩基)甲基]草酸酰胺(BTMO) 作为Cu2O催化氮杂环的N-芳基化的高效配体[5]Cu2O/BTMO是一种与次等反应活性(杂)芳基氯化物进行Goldberg 酰胺化反应的有效催化剂体系，目前–铜催化还没有有效的文献报道。该反应对各种官能化(杂)芳基氯化物和各种芳香族和脂肪族初级酰胺都适用，产率可达70%以上。此外，该催化体系还实现了内酰胺和恶唑烷酮的芳基化反应。图11 Cu2O/BTMO催化(杂)芳基氯化物与酰胺的偶联反应6. BFMO及N,N -双(2,4,6-三甲氧基苯基)草酰胺(BTMPO) 增强了(杂)芳基溴代物与苯胺和仲胺的铜催化偶联的催化活性[6]BFMO是一种价格低廉、使用方便的双齿配体，对于促进铜催化的苯胺和环仲胺的N-芳基化反应非常有效。该方法能够在60-80℃的温度下，在0.5 mol %的催化剂浓度中，使多种(杂)芳基溴代化合物与各种(杂)芳基胺和环仲胺发生偶联（如下图）。图12 CuI/ BFMO催化(杂)芳基溴代物与(杂)芳基氨基的偶联以N,N‘-双(2,4,6-三甲氧基苯基)草酸酰胺(BTMPO)为配体，催化(杂)芳基溴代物与空间位阻较大的无环仲胺偶联，收率达到80%以上，催化剂用量为1mol%CuI和1 mol%BTMPO。实验结果如下图所示。图13 CuI/ BTMPO催化(杂)芳基溴代物与无环仲胺的偶联7. N,N’-双(4-羟基-2,6-二甲基苯基)草酰胺(BHMPO)作为Cu(acac)2催化(杂)芳基卤化物的羟基化反应的最佳配体[7]根据课题组之前的研究，通过筛选各种草酰二胺配体，确认N,N‘ -双(4-羟基-2,6-二甲基苯基)草酸酰胺(BHMPO) 作为Cu(acac)2催化（杂）芳基卤化物的羟基化反应的最佳配体。在130℃时，许多带有供电子基团或吸电子基团的（杂）芳基氯化物都能很好地生成相应的酚类和羟基化的（杂）芳烃，催化结果如下图所示。图14 BHMPO作为配体参与铜催化(杂)芳基氯化物的羟基化反应当反应活性更强的（杂）芳基溴代物和碘代物作为底物时，在较低的催化浓度(0.5 mol % Cu)下，羟基化反应在相对较低的温度(分别为80和60 ℃)下完成，催化结果如下图所示。图15 BHMPO作为配体参与铜催化(杂)芳基溴化物（上）和(杂)芳基碘化物（下）的羟基化反应值得注意的是，在这些放大实验中可以进一步减少催化剂的浓度，缩短反应时间。例如,1 - (3-氯苯)-苯乙酮的羟基化反应在20 mmol量级，更易在24小时完成，而使用的催化剂和配体只有2mol%，而3-溴-1-碘苯在20 mmol量级的完全羟基化反应只需12小时。这些额外的优点使目前的方法对于大批量生产酚类更有吸引力。图16 放大羟化反应8. N1 -((1,1’联苯)-N2-苯乙基乙二酰胺 2-yl)（L9）为CuI催化(杂)芳基氯化物与酚类偶联的最佳配体[8]经过筛选不同催化配体和优化偶联反应条件，课题组发现草酰二胺分子L9可作为CuI催化(杂)芳基氯化物与酚类偶联的最佳配体，反应可在120℃下顺利进行。在这一过程中，L9是比双(烯丙基)取代的草酸酰胺更有效的配体。富电子芳基、贫电子芳基和(杂)芳基氯化物在一定范围内均能得到相应的偶联产物。富电子酚和有限范围内的贫电子酚作为底物均可获得满意的转化率。低至1.5 mol%的催化剂和配体浓度足以使这些反应进行放大工艺合成。图17 L9作为配体参与铜催化(杂)芳基氯化物与酚类的偶联反应9. N,N’-双(2-苯基苯基)草酸(BPPO)或N-(2-苯基苯基)-N -苄基草酸(PPBO)作为CuI催化酚类和(杂)芳基卤化物偶联形成二芳基的高效配体[9]在研究L9配体参与的酚类和(杂)芳基卤化物偶联反应后，课题组继续的研究发现以DMF或MeCN为溶剂，在CuI/ BPPO或CuI/ PPBO的催化下，在90℃的温度下，酚和(杂)芳基溴化物或碘化物偶联形成二芳基的完全转化最低只需要0.2 mol %的CuI和配体，这是一般Cu/配体催化生成二芳基醚的最低催化浓度，催化反应结果如下。图18 CuI/ BPPO（上）或CuI/ PPBO（下）的催化下酚和(杂)芳基卤化物偶联形成二芳基10. N, N’-二苄氧乙二酰胺（DBO）作为铜催化杂芳基卤化物与杂苯胺类偶联的最佳配体[10]图19 FDA批准的含氮杂芳基异苯胺骨架结构的药物分子氮杂苯胺是一种多用途的药物骨架，特别是在分子激酶抑制剂（SMKIs）中应用尤其广泛。自2001年伊马替尼经FDA批准应用于慢性粒细胞白血病（CML）和胃肠道间质瘤（GIST）的靶向治疗，选择性激酶抑制剂的开发已成为工业界和学术界研究的热点。因此，开发简单高效的N-杂环药物的合成方法具有重要意义。马大为课题组证明DBO作为一种强有力的配体，可促进杂芳环胺与（杂）芳基卤化物的Cu催化偶联。对于（杂）芳基氯化物，反应温度在130°C下，用5mol%CuBr和10mol%DBO即可催化发生的反应。对于（杂）芳基溴/碘化物，在80-100°C下，1mol%CuI和2mol%DBO催化可发生偶联反应。反应底物适用性广泛且均能取得良好的收率。以嘧啶-2-胺与4-氯茴香醚为底物，研究了不同的草酸二酰胺配体对于这类催化偶联反应中的影响。如下图所示，初步使用BTMO（L1）作为铜催化酰化芳基氯化物的配体， T-BuONA和4A分子筛（entry1）作为助催化剂，反应温度为120°C，以18%的收率生成偶联产物3a。这一反应收率在使用PMPBO(L2)和BMNO (L3)相继作为铜催化反应的配体时得到持续改善。此后，研究人员改变铜盐（entry4-7）以期进一步提高反应收率，结果并不理想，研究回归到催化配体的筛选，令人惊讶地发现， DPEO（L4）作为配体时催化反应的产率较低（entry8）。但当DBO（L5）作为配体（entry9）时，收率较高。该现象进一步表明，草酸二胺的结构细微变化会极大地影响它们的催化能力。以DBO为配体，如果在130°C下进行反应（entry11），反应产率可提高到86%，但如果使用BNMO，反应温度从120℃升高到130℃收率则不会发生变化（比较entry3和10）。在相同的条件下，N、N’-二甲基乙二胺（L6）和1,10-菲啉（L7）两种以前用于杂苯胺芳基化的配体在该反应中则没有发生催化反应（entry12、13）。这些结果表明，以草酸二酰胺为配体是杂苯胺与芳基氯化物成功偶联的关键。进一步的研究显示，用t-BuONa替换t-BuOK的溶液环境得到了类似的结果（entry14）。有趣的是，降低CuBr和配体的催化负载量，反应产率会有所下降（entry15），而如果只降低CuBr的催化浓度（entry16），则观察到产率增加。综上所述，反应的最佳条件是以5mol%CuBr为催化剂，10mol%DBO为配体，t-Buona为碱，在130°C进行反应。图20 最佳反应条件及DBO配体的探索建立最佳反应条件后，研究人员用各种杂苯胺和（杂）芳基氯化物对该反应的适用性进行探索，结果下图所示。图21 反应底物适用性探索如图21所示，可知2-氨基嘧啶与富电子基或吸电子基团的（杂）芳基氯化物的反应可以69%~84%的产率顺利得到偶联产物。通过将相应的苯胺与三种芳基氯化物（3f-3h）偶联，可以很容易地引入存在于伊马替尼和尼洛替尼中的4-(吡啶-3-基)嘧啶-2-氨基骨架。此外，3,5-二甲基-2-氨基嘧啶也能很好地进行反应，使得3i的产率达到81%。此外，4-氨基喹唑啉（3j-k）、2-氨基吡嗪（3l）、2-氨基喹唑啉（3m）等其他杂芳环胺也能够很好的发生反应。当使用活性更大的芳基溴/碘代物作为偶联底物时，研究发现以CuI为铜源，DBO为配体，T-BuOK为碱是反应的最佳组合。在这种情况下，只需要1mol%CuI和2mol%DBO就可以确保在100°C（溴化物）或80°C（碘化物）下完成偶联反应。该项研究证明了一种非常简单的配体，N,N‘-二苄氧乙二酰胺，可以促进具有挑战性的铜催化C-N异族苯胺与（杂）芳基卤化物的偶联。新的催化体系不仅可以与活性较低的（杂）芳基氯化物的偶联，而且与（杂）芳基溴化物/碘的偶联反应条件更加温和（相对较低的催化负载量，反应温度较低）。鉴于N-芳基杂苯胺在药物研发中的重要性，该合成方法在有机合成中有相当广阔的应用前景。11. BNMO/DEPO作为铜催化芳基卤化物与醇偶联的最佳配体[11]烷基芳基醚是众多天然产物和具有各种重要功能的分子砌块中常见的结构。特别是，它们在药物分子中非常常见，并且在畅销药物的结构中屡见不鲜，如下图所示。图22 含有烷基芳基醚结构的畅销药物因此，更通用和反应条件温和的烷基芳基醚合成方法的发展引起了学术界和工业界的持续关注。在过去的二十年中，过渡金属催化的易得的卤代芳烃与醇的碳氧偶联反应是对已有醚合成方法的有益补充。然而，钯和膦配体的成本问题以及相关催化体系的稳定性差限制了其反应的适用性；同样的，镍和膦配体催化反应受制于使用昂贵的膦配体和对富含电子的芳基溴化物和氯化物具有惰性。相比于Pd 和 Ni的催化偶联反应，铜催化的芳基卤化物与醇的反应在经济性和操作便利性方面是更有吸引力的方法，虽然与 Pd 和 Ni 相比更容易发生还原消除副反应，但其底物范围仅限于芳基碘化物。当空间张力大或无环的仲醇与芳基碘化物偶联时，需要苛刻的反应条件 (140℃) 和与底物等当量的配体才能以良好的产率获得理想的偶联产物。对于芳基溴化物，使用纯醇作为溶剂和底物，高温（超过 110℃）对于确保令人满意的转化率是必要的。即使在这些条件下，很少有仲醇能发生偶联反应。此外，迄今为止，还没有采用相对廉价的芳基氯化物的成功例子的报道。图23 改进后的碳氧偶联反应1) 草酸二酰胺配体DPEO和BNMO的辅助下，Cu催化的未活化芳基氯化物和溴化物的烷氧基化反应马大为课题组接下来系统地研究了一些新的草酸二酰胺配体（如下图所示），它们在促进Cu催化的其他亲核分子的芳基化反应方面表现出优异的催化活性。在两种简单的草酸二酰胺配体DPEO和BNMO的辅助下，Cu催化的未活化芳基氯化物和溴化物的烷氧基化反应可在60-100℃下进行。只需要2-3个当量的醇类与之反应便可得到相应的烷基芳基醚。该研究中，叔丁醇首次被证明是铜催化的偶联反应的配体，在室温下参与催化芳基碘化物的烷氧基化反应。此外，许多碳水化合物衍生物可用于这种偶联反应，以29-98%的收率合成了相应的碳水化合物-芳醚。图24 筛选的配体种类图25 反应的底物适用性2) 改进后的乌尔曼反应在药物合成方面的应用如上左图所示，与相应的芳基溴联用，可在多克的合成量级制备3ai (pramoxine)和3aj。前者是一种传统的局麻药，后者是制造治疗耐多药结核病药物delamanid的常用原料。原有制备3aj的方法是利用Mistunobu反应，这一反应因为使用偶氮二羧酸酯和膦试剂会产生大量的废料。上述改良后的碳氧偶联方法，也适用于抗抑郁剂度洛西汀的关键中间体3ak的合成。多氟烷基芳醚3al是合成血清素6 (5- HT6)受体拮抗剂依达罗定的中间体，该药物目前正处于阿尔茨海默病治疗的III期临床试验。此前，该化合物是通过威廉姆森醚合成得到的，原有工艺中需要用对三酰氯对CHF2CF2CH2OH进行预活化。在该项研究中，直接溴代芳烃可以与CHF2CF2CH2OH直接偶联，以高收率89%得到3al。也可与CF3CH2OH偶联得到另一种氟化烷基芳醚3am，该分子可能是制备抗心律失常药氟卡胺的中间体，偶联反应收率为89%。注：图片来源于参考文献参考文献：[1] J. Am. Chem. Soc. 2015, 137, 11942−11945[2] Org. Lett. 2015, 17, 5934−5937[3] Org. Lett. 2017, 19, 11, 2809-2812[4] Adv. Synth. Catal. 2017, 359, 1631 – 1636[5] Org. Lett. 2017, 19, 4864−4867[6] J. Org. Chem. 2017, 82, 12603−12612[7] J. Am. Chem. Soc. 2016, 138, 13493−13496[8] Angew. Chem. Int. Ed. 2016, 55, 6211 –6215[9] J. Org. Chem. 2017, 82, 4964−4969[10] Org. Lett. 2019, 21, 17, 6874-6878[11] J. Am. Chem. Soc. 2019, 141, 8, 3541-3549本文系药明览博网原创文章，欢迎分享，转载需授权！长按识别二维码，发现更多新药研发的新方法

2024-12-12

·PRNewswire

AZURITY PHARMACEUTICALS, INC. ANNOUNCES AVAILABILITY OF AZMIRO™ (testosterone cypionate) injection for intramuscular use, CIII

WOBURN, Mass., Dec. 12, 2024 /PRNewswire/ -- Azurity Pharmaceuticals announced today the availability of Azmiro™, the first and only FDA-approved prefilled testosterone cypionate injection. Azmiro is an androgen indicated for testosterone replacement therapy in males for conditions associated with a deficiency or absence of endogenous testosterone. "Azurity's purpose is to serve overlooked patients by developing innovative dose forms and formulations to serve unmet needs," said Richard Blackburn, CEO of Azurity Pharmaceuticals. "The commercial availability of Azmiro offers a convenient prefilled option for healthcare providers administering testosterone to patients." Testosterone cypionate intramuscular injections are commonly used as a testosterone replacement therapy for patients with low testosterone by drawing up testosterone cypionate doses from a vial, then administering with a syringe. Azmiro provides an FDA-approved prefilled option now available as a 200 mg/mL single dose syringe. Safety and efficacy of Azmiro in men with age-related hypogonadism have not been established. For full Azmiro prescribing information, including medication guide, please go to azmiro.com. About Azurity Pharmaceuticals, Inc. Azurity specializes in providing innovative, high-quality medicines that serve overlooked patients. We supply a large number of products to treat a wide range of medical conditions. These include anti-infective, cardiovascular/cardiology, central nervous system/cerebrovascular, endocrinology, gastrointestinal, immunology, and oncology medicines. Many of our medicines are dose-form innovations for patients with needs that are not met by other available products. Our medicines have benefited millions of people. For more information, visit . PP-AZO-US-0033 SOURCE Azurity Pharmaceuticals, Inc. WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

上市批准

2023-03-16

·Pharmaceutical Technology

Legal challenges put off label use of gender affirming care drugs in jeopardy

Credit: Shutterstock/ Chaos810 Earlier this week, the Florida Senate advanced a bill to restrict gender-affirming care for transgender minors. The bill is one of many that are currently being discussed in different states. Free Report How is the Biopharmaceutical industry evolving? 2021 was a year of continued innovation and change in the Biopharmaceutical industry. As the COVID-19 pandemic continues to take its toll on businesses worldwide, it’s time to look for new ways to create value, prepare for the future, and remain competitive in the ever-changing landscape. GlobalData’s expansive report examines the business environment and trends that shape the Biopharmaceutical industry. We highlight the most impactful emerging technologies, as well as the industry, regulatory, and macroeconomic factors that influence growth prospects. Access the report to: Benchmark the impact of major themes on the Biopharmaceutical industry. Gain a deeper "on the ground" perspective through exclusive opinions and analysis from industry respondents. Evaluate the effects of COVID-19 on the sector. Download the full report to understand what to expect and how to align your strategies for success. 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Visit our privacy policy for more information about our services, how we may use, process and share your personal data, including information on your rights in respect of your personal data and how you can unsubscribe from future marketing communications. Our services are intended for corporate subscribers and you warrant that the email address submitted is your corporate email address. Thank you. Please check your email to download the Report. Many politicians have cited doubts about the potential “harm” caused by puberty blockers and hormone therapies associated with gender-affirming care and concerns about incorrect treatment as major factors. However, health specialists refute most safety concerns for the use of drug classes as part of gender affirming care, citing years of research and care. Dr. Barry DeCoster, PhD, an associate professor of bioethics at the University of Michigan, describes gender affirming care as “safe and effective” for most patients. Most drugs used here are prescribed off-label, and experts say pharmaceutical companies remain hesitant to conduct clinical trials studying gender-affirming care. This has pushed clinicians to explore different routes to prove the validity of these drugs. The World Health Organization (WHO) defines gender-affirming care as a range of social, psychological, behavioural, and medical interventions that are “designed to support and affirm an individual’s gender identity” when it conflicts with the gender they were assigned at birth. The laws proposed in several bills range in their potential influence; from restricting the prescription of gender-affirming drugs to criminalising the use of such drugs to allowing states to pursue lawsuits against parents who allow children to access such treatments. Dr Lisa Campo-Engelstein, a bioethicist, predicts that these factors and subsequent restrictions on statewide healthcare coverage will heavily restrict patient access to gender-affirming care. Campo-Engelstein is the director of the Institute for Bioethics & Health Humanities at the University of Texas Medical Branch, Galveston. With restricted access and reduced prescription of puberty blockers and hormone therapies, the impact on pharmaceutical companies manufacturing these therapies also remains unclear. Standards of care for gender-affirming therapies The global standards for gender-affirming medical practices stem from the World Professional Association for Transgender Health (WPATH)’s yearly guidelines . WPATH’s recommendations are based on “the best available science and expert professional consensus” to give “safe and effective pathways” for transsexual, transgender, and gender-nonconforming people . WPATH suggests an individualised approach to treating gender dysphoria. Generally, individuals first take on social gender-affirmation changes. Dr Sean Cahill, PhD, the associate editor of the global, peer-reviewed journal LGBT Health, says “for most young people, healthcare provided doesn’t even go beyond that [social affirmation of gender identity], but a lot of people… are misrepresenting what gender affirming care looks like in this country”. Following this, they may progress to the use of puberty blockers. After a minor has been on puberty blockers for two to three years, they may have the option to use hormone therapies upon further evaluation. Puberty blockers are used in gender affirming care to delay the onset of puberty for gender dysphoric children of any gender. These drugs do not tend to have permanent effects and only cause a pause in puberty. While hormone therapies are allowed in the US, the age limit for this is dependent on the geographical area. Standard puberty blockers include Gonadotrophin Releasing Hormone (GnRH) analogues like Trelstar (triptorelin), Supprelin (Histrelin), and Zoladex (Goserelin), are only prescribed off label in the US and UK for gender affirming care. For example, Ontario, Canada-based Verity Pharmaceuticals’s Trelstar was FDA approved for palliative treatment of advanced prostate cancer and the other two are indicated for treating central precocious puberty and endometriosis, respectively. Several companies that produce commonly used puberty blockers such as Vantas Pharmaceuticals, Endo International and TerSera Therapeutics, have remained silent on the ongoing debate. Additionally, hormone therapies—testosterone to “masculinise” and/or transition to men, and oestrogen for transitioning to women and/or “feminising” the body—are an integral part of the plan. Testosterone stops menstrual cycles, decreases the ovaries’ ability to make oestrogen and more, while oestrogen allows individuals to develop breasts, rounder hips and changes to the reproductive system. The most commonly used testosterones in the US include Endo International’s Delatestryl (testosterone enanthate) and Aveed (testosterone undecanoate), and Pfizer’s Depo-testosterone (testosterone cypionate). These changes can be irreversible and can take up to five years to reach maximum effect. Common oestrogen therapies are mostly oestradiols such as Novartis’ Vivelle-Dot, Ascend Therapeutics’ Estrogel, and Teva Pharmaceuticals’ Gynodiol. Oestrogen hormone therapies are often approved for restoring hormone levels for cisgendered women, to reduce symptoms such as hot flushes and vaginal dryness. Dr. Edmund Horowicz PhD, a lecturer in medical law and ethics at the University of Liverpool, counters discourse from those such as the Norwegian Healthcare Investigation Board UKOM , that characterises puberty blockers as “experimental” and untrustworthy due to their off-label prescription. One of the reasons why organisations, including pharma companies, do not enter this debate is because these drugs are used off label, says Horowicz. As these drugs are not licensed for the specific indication of gender-affirming care, collecting safety data on off-label use is not viewed as a priority. Cahill says health centers across the nation, like his, see a sizable transgender population, and would be able to easily conduct longitudinal drug studies investigating safety measures and patient satisfaction. But the funding is not there, he adds. The onus for funding would most likely be on government agencies like the National Institutes of Health (NIH), says Cahill. Moreover, there are some logistical barriers in designing such studies. While it is important to run randomised placebo-controlled trials, giving participants sham gender affirming care, for example, would worsen mental distress associated with gender dysphoria, says Horowicz. There might also be ethical considerations for denying care and some subjects may also drop out of studies. Still, while the long-term impact of puberty blockers on bone-density and muscular skeletal development still needs to be studied, Horowicz asserts this should be viewed as a risk associated with a drug, similar to all other drugs. In Georgia’s bill , the legislators reason that the bill would be necessary under the “do no harm” principle, expressing safety concerns for minors. Due to a lack of long-term data into the possible impacts of these drugs, some people have proposed a possible solution of only prescribing these drugs within studies until more data arises. But this would restrict these drugs to only those who choose to be trial participants, creating further ethical conundrums, says Horowicz. Furthermore, Horowicz states that clinical frameworks, such as WPATH’s guidelines, are already based on evidence from trials of these well-established drugs. New studies for this use would be “more to satisfy those who are concerned about the provision of puberty blockers than any kind of traditional expected model of pharmacological research”. Possible consequences Last year, the Biden administration proposed the implementation of a rule in section 1557 , that would protect against limiting access to care by stating that “categorically refusing to provide treatment to an individual based on their gender identity is prohibited discrimination”. However, the recent state-specific gender affirmation legislations may look to contradict this. For example, in Florida, the Agency for Health Care Administration has prohibited Medicaid from covering any kind of gender-affirming care procedures like hormone therapies. Campo-Engelstein says some states like Texas don’t allow coverage for gender-affirming care through public systems. However, she points out that gender affirmation practices are still completely legal in the context of intersex “correction”, yet lawmakers contradict their use for transgender individuals. An immediate consequence of the possible legal ramifications of the bills is a shift in patient care and healthcare coverage, particularly for publicly funded hospitals. A bellwether for which states may see major changes in drug prescription and coverage, may be the ones that saw changes in access to abortion following the Supreme Court overturning Roe v Wade . “States that are banning abortion are going to be more likely to ban gender affirming care, because they’re both motivated by the same social and political values,” says Campo-Engelstein. DeCoster says the lack of consultation with clinicians and patients in deciding these legislations does a disservice to those most affected by the new laws. “We should be having a health care system that is helping support and to raise up people to give them what they need,” he says. Free Report How is the Biopharmaceutical industry evolving? 2021 was a year of continued innovation and change in the Biopharmaceutical industry. As the COVID-19 pandemic continues to take its toll on businesses worldwide, it’s time to look for new ways to create value, prepare for the future, and remain competitive in the ever-changing landscape. GlobalData’s expansive report examines the business environment and trends that shape the Biopharmaceutical industry. We highlight the most impactful emerging technologies, as well as the industry, regulatory, and macroeconomic factors that influence growth prospects. Access the report to: Benchmark the impact of major themes on the Biopharmaceutical industry. Gain a deeper "on the ground" perspective through exclusive opinions and analysis from industry respondents. Evaluate the effects of COVID-19 on the sector. Download the full report to understand what to expect and how to align your strategies for success. 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上市批准

100 项与环戊酸睾酮相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
D00957	环戊酸睾酮	G03BA03	DB13943

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
睾酮缺乏	美国	Azurity Pharmaceuticals, Inc.	2022-06-02
更年期	-	-	1999-08-26
性腺机能减退	-	-	1999-08-26
乳腺癌	-	-	1999-08-01
乳腺疾病	-	-	1999-08-01
少精子症	-	-	1999-07-23
骨质疏松症	-	-	1999-07-18
无睾症	-	-	1999-07-14
青春期延迟	-	-	1999-07-12

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临床结果

适应症

分期

评价

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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


NCT04558866 (ExBAT trial/LACOG 0620, ASCO_GU2025) 人工标引	临床2期	转移性去势抵抗性前列腺癌	48	testosterone cypionatetestosterone cypionate 400 mg on day 1, followed by oral darolutamide 1200 mg/day from day 29 to day 56, followed by a washout period of 7 days, in 63-day cyclesdarolutamide 1200 mg/day from day 29 to day 56, followed by a washout period of 7 days, in 63-day cycles	窪廠構遞廠鬱憲窪蓋積(製願範衊製餘襯夢淵齋) = 遞鹹蓋遞夢構艱醖觸膚鬱顧窪膚壓淵鹹製鏇製 (範餘遞蓋繭獵廠鹹襯鏇, 26.3 ~ 55.0) 更多	积极	2025-02-13
NCT02995330 (CTgov)	临床1期	转移性去势抵抗性前列腺癌	3	Bone marrow transplantation+Cytoxan+testosterone cypionate	願獵齋齋憲鹹願壓膚糧 = 壓窪積蓋範觸鏇網遞願衊蓋積鏇壓觸蓋繭膚膚 (顧顧襯壓窪範積鹹夢衊, 艱選製範積觸夢構範夢 ~ 獵獵獵膚廠製顧網願簾) 更多	-	2024-02-13
NCT04439799 (CTgov)	临床4期	继发性睾丸衰竭 \| 无睾症	81	Testosterone Cypionate 200 Mg/ML (Testosterone Cypionate Group)	糧網積繭鬱簾餘衊鬱夢(餘餘積壓鏇鑰顧鹽膚構) = 簾範憲網範範選廠膚憲選積糧淵製觸艱膚觸餘 (鹽鑰齋積糧選遞遞憲範, 醖膚鏇鏇膚廠範觸鏇襯 ~ 壓衊廠壓構鏇願醖構鏇) 更多	-	2023-12-13
				Intranasal Testosterone (Natesto Group)	糧網積繭鬱簾餘衊鬱夢(餘餘積壓鏇鑰顧鹽膚構) = 夢憲衊夢顧鹹繭積餘鬱選積糧淵製觸艱膚觸餘 (鹽鑰齋積糧選遞遞憲範, 艱艱壓繭觸網醖醖糧顧 ~ 積衊顧選簾顧醖衊顧醖) 更多
NCT02090114 (RESTORE, CTgov)	临床2期	前列腺癌 \| 去势敏感前列腺癌 \| 去势抵抗性前列腺癌 ... 更多	112	Enzalutamide+Testosterone Enanthate+Testosterone cypionate (Cohort A:Post-enzalutamide)	壓構壓鑰選築鑰願鏇蓋 = 夢積膚選製選繭艱構糧艱蓋糧鏇鏇觸構襯繭簾 (獵鬱遞襯繭範窪繭鹽範, 糧夢廠築獵觸繭衊選鹹 ~ 襯艱夢膚衊餘願繭繭齋) 更多	-	2022-06-27
				Testosterone Enanthate+Abiraterone Acetate+Testosterone cypionate (Cohort B: Post-abiraterone)	壓構壓鑰選築鑰願鏇蓋 = 顧膚鏇構廠襯獵觸衊顧艱蓋糧鏇鏇觸構襯繭簾 (獵鬱遞襯繭範窪繭鹽範, 淵淵廠構願鹹淵獵觸壓 ~ 獵鬱獵觸網繭窪憲齋遞) 更多
NCT03554317 (COMBAT, ASCO2022) 人工标引	临床2期	转移性去势抵抗性前列腺癌	45	Testosterone Cypionate(BAT) + Nivolumab	壓淵襯膚製糧觸蓋齋鏇(衊築齋衊憲構壓鹽構鹽) = 繭選築糧繭願積廠獵醖衊願選遞顧夢網積醖蓋 (艱積鹹糧願顧窪鏇夢遞, 26 ~ 56) 更多	积极	2022-06-02
AUA2021	N/A	多发性内分泌瘤病 serum total testosterone (TT) \| hematocrit (HCT) \| estradiol (E2) ... 更多	263	Intramuscular Testosterone Cypionate	簾築願簾糧鑰繭淵衊蓋(襯齋餘築餘鑰顧鏇夢膚) = 膚鑰鬱衊鏇鏇壓鹹鹹糧網襯鹽蓋廠繭遞衊構製 (築鏇衊觸醖積壓鹽範簾 )	-	2021-09-01
				Subcutaneous Testosterone Enanthate	簾築願簾糧鑰繭淵衊蓋(襯齋餘築餘鑰顧鏇夢膚) = 鬱遞製構積鬱鏇淵艱齋網襯鹽蓋廠繭遞衊構製 (築鏇衊觸醖積壓鹽範簾 )
NCT02408445 (CTgov)	临床4期	先天性睾丸发育不全综合征	20	testosterone cypionate 200mg/ml (Testosterone Treatment)	蓋顧鑰範範選壓憲獵醖(糧積壓築鹽壓醖餘製觸) = 窪衊衊鑰鹹襯築範築構壓築築簾積夢構餘繭蓋 (鑰築遞糧鏇醖顧鬱製簾, 0.65) 更多	-	2020-04-15
				testosterone (No Treatment)	蓋顧鑰範範選壓憲獵醖(糧積壓築鹽壓醖餘製觸) = 衊網憲繭壓糧壓衊獵願壓築築簾積夢構餘繭蓋 (鑰築遞糧鏇醖顧鬱製簾, 0.62) 更多
NCT02286921 (TRANSFORMER, CTgov)	临床2期	去势抵抗性前列腺癌	222	Testosterone Enanthate+Testosterone cypionate (Arm A: Testosterone Cypionate or Testosterone Enanthate)	觸積鹽積觸夢蓋膚顧醖(網積膚鹽製遞膚願醖繭) = 簾夢顧艱觸鹽淵鏇築製鹹衊鏇醖壓製憲糧簾艱 (餘製襯願繭鬱淵鏇窪鏇, 構鑰艱鹹鏇夢夢網築廠 ~ 壓衊繭艱顧繭鏇簾鏇鏇) 更多	-	2019-05-01
				Enzalutamide (Arm B: Enzalutamide)	觸積鹽積觸夢蓋膚顧醖(網積膚鹽製遞膚願醖繭) = 積願鏇壓淵積壓鬱願憲鹹衊鏇醖壓製憲糧簾艱 (餘製襯願繭鬱淵鏇窪鏇, 網蓋構繭鹽壓積夢蓋糧 ~ 簾獵窪繭廠鬱窪餘築鹹) 更多
NCT01750398 (BAT \| BATMAN study, CTgov)	临床2期	复发性前列腺癌	33	Testosterone	窪蓋衊積膚遞顧鹹齋餘 = 簾網夢繭製範鹽壓夢構憲築蓋窪遞鹹願觸襯餘 (衊醖艱醖範觸鏇獵顧餘, 艱簾衊淵觸憲糧願網蓋 ~ 壓糧築糧淵醖構願蓋齋) 更多	-	2016-12-05