Background:
Proteus syndrome is a rare overgrowth disorder. Most people begin to have symptoms between 6 months and 2 years of age. There are very few living adults with this disease. There is also no known treatment for it. Researchers want to see if a new drug can slow down or stop overgrowth in people with Proteus syndrome.
Objective:
To learn if miransertib is a safe and effective treatment for Proteus syndrome.
Eligibility:
People ages 3 and older with Proteus syndrome
Design:
Participants will be screened with a medical checkup. They will answer questions about their medical history and current health. They will have a physical exam with vital signs. They will have an electrocardiogram to measure their heartbeat. They will give blood and urine samples. They will repeat the screening tests during the study.
Participants will take a miransertib pill once a day. They will bring their empty pill bottles with them to the NIH when they visit. If they can t swallow a pill, researchers will try to find other ways for them to take the drug.
Participants will have X-rays, ultrasounds, and imaging scans. Photos may be taken of their feet and other parts of the body that have or develop signs of Proteus syndrome.
Participants will have lung function tests to measure how much and how fast air moves out of their lungs.
Participants will complete surveys about their levels of pain, physical functioning, and quality of life.
Participants may have additional tests performed to assess their individual disease. They may have consultations with other specialists.
Participation lasts about 4 years. Participants will have 20-30 visits at the NIH....

开始日期2022-05-20

申办/合作机构

National Human Genome Research Institute

NCT04980872 / Active, not recruiting临床2期

A Multicenter, Open-label, Phase 2, Extension Trial to Study the Long-term Safety in Participants With PROS or Proteus Syndrome Who Are Currently Being Treated With Miransertib in Other Studies

This is a study of the safety and tolerability of oral miransertib (MK-7075) administered to participants at least 2 years of age with phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA)-related overgrowth spectrum (PROS) or Proteus Syndrome (PS). This is an extension of other miransertib studies (MK-7075-002 [NCT03094832] or ArQule CU/EAP [NCT03317366]), and may also enroll participants who are approved for MK-7075-002 but have not yet started miransertib therapy.

开始日期2021-11-02

申办/合作机构

Merck Sharp & Dohme Corp.

EUCTR2021-001369-19-IT / Unknown status临床2期

A Multicenter, Open-label, Phase 2, Extension Trial to Study the Long-term Safety in Participants With PROS or Proteus Syndrome Who Are Currently Being Treated with Miransertib in Other Studies - Miransertib Extension Study for PROS / PS Patients

开始日期2021-10-20

申办/合作机构-

100 项与 Miransertib 相关的临床结果

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100 项与 Miransertib 相关的转化医学

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100 项与 Miransertib 相关的专利（医药）

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项与 Miransertib 相关的文献（医药）

2023-12-01·Molecular Diversity

Identification of allosteric inhibitor against AKT1 through structure-based virtual screening

Article

作者: Karunakaran, Keerthana ; Muniyan, Rajiniraja

AKT (serine/threonine protein kinase) is a potential therapeutic target for many types of cancer as it plays a vital role in cancer progression. Many AKT inhibitors are already in practice under single and combinatorial therapy. However, most of these inhibitors are orthosteric / pan-AKT that are non-selective and non-specific to AKT kinase and their isoforms. Hence, researchers are searching for novel allosteric inhibitors that bind in the interface between pH and kinase domain. In this study, we performed structure-based virtual screening from the afroDB (a diverse natural compounds library) to find the potential inhibitor targeting the AKT1. These compounds were filtered through Lipinski, ADMET properties, combined with a molecular docking approach to obtain the 8 best compounds. Then we performed molecular dynamics simulation for apoprotein, AKT1 with 8 complexes, and AKT1 with the positive control (Miransertib). Molecular docking and simulation analysis revealed that Bianthracene III (hit 1), 10-acetonyl Knipholonecyclooxanthrone (hit 2), Abyssinoflavanone VII (hit 5) and 8-c-p-hydroxybenzyldiosmetin (hit 6) had a better binding affinity, stability, and compactness than the reference compound. Notably, hit 1, hit 2 and hit 5 had molecular features required for allosteric inhibition.

2023-09-01·European Journal of Ophthalmology

Multimodal ocular imaging in Proteus syndrome

Article

作者: Scartozzi, Luca ; Rizzo, Stanislao ; Mattei, Roberta ; Piccinni, Fabrizio ; Mosca, Luigi ; Salerni, Annabella ; Onesimo, Roberta ; Zampino, Giuseppe ; Leoni, Chiara

In this report we illustrate the ophthalmologic assessment of two patients affected by Proteus Syndrome (PS), an extremely rare genetic disorder. Case #1 describes a 26 year old male patient followed for multiple ophthalmic anomalies: a limbal dermoid cyst, a unilateral cataract, bilateral nystagmus, severe myopia and unilateral optic nerve head drusen. Case #2 describes a 20 year old female patient referred to our Ophthalmology Department for a routine ophthalmologic evaluation after being treated for 3 years with Miransertib (an experimental AKT-pathway inhibitor). Both patients underwent a complete ophthalmologic examination and a multimodal imaging evaluation. The multimodal imaging approach has revealed useful to evaluate both cases in detail and to keep track of disease evolution over time, moreover providing helpful features to further characterize this rare syndrome.

2023-08-03·Medicina (Kaunas, Lithuania)

The Synergistic Effect of Zuogui Pill and Eldecalcitol on Improving Bone Mass and Osteogenesis in Type 2 Diabetic Osteoporosis.

Article

作者: Meng, Lingxiao ; Rong, Xing ; Kou, Yuying ; Shi, Tuo ; Gao, Ruihan ; Cui, Yajun ; Hu, Sumin ; Li, Minqi ; Liu, Ting

Background and Objectives: The incidence of diabetic osteoporosis, an important complication of diabetes mellitus, is increasing gradually. This study investigated the combined effect of the Zuogui pill (ZGP) and eldecalcitol (ED-71), a novel vitamin D analog, on type 2 diabetic osteoporosis (T2DOP) and explored their action mechanism. Materials and Methods: Blood glucose levels were routinely monitored in db/db mice while inducing T2DOP. We used hematoxylin and eosin staining, Masson staining, micro-computed tomography, and serum biochemical analysis to evaluate changes in the bone mass and blood calcium and phosphate levels of mice. Immunohistochemical staining was performed to assess the osteoblast and osteoclast statuses. The MC3T3-E1 cell line was cultured in vitro under a high glucose concentration and induced to undergo osteogenic differentiation. Quantitative real-time polymerase chain reaction, Western blot, immunofluorescence, ALP, and alizarin red staining were carried out to detect osteogenic differentiation and PI3K-AKT signaling pathway activity. Results: ZGP and ED-71 led to a dramatic decrease in blood glucose levels and an increase in bone mass in the db/db mice. The effect was strongest when both were used together. ZGP combined with ED-71 promoted osteoblast activity and inhibited osteoclast activity in the trabecular bone region. The in vitro results revealed that ZGP and ED-71 synergistically promoted osteogenic differentiation and activated the PI3K-AKT signaling pathway. The PI3K inhibitor LY294002 or AKT inhibitor ARQ092 altered the synergistic action of both on osteogenic differentiation. Conclusions: The combined use of ZGP and ED-71 reduced blood glucose levels in diabetic mice and promoted osteogenic differentiation through the PI3K-AKT signaling pathway, resulting in improved bone mass. Our study suggests that the abovementioned combination constitutes an effective treatment for T2DOP.

项与 Miransertib 相关的新闻（医药）

2023-04-27

·FierceBiotech

Merck reveals HIV combo trial is back in the running after FDA partial hold lifted

Merck executives said on a first-quarter earnings call that the company is restarting a phase 2 trial testing a combination of islatravir and Gilead’s lenacapavir. The middle of Merck & Co.’s clinical batting order took center stage on the company’s first-quarter earnings call, including a phase 2 HIV combo therapy that once again returned to the lineup. The Big Pharma has resumed a phase 2 study of MK-8591D, an oral regimen of islatravir and Gilead’s Sunlenca, executives said on a call with analysts Thursday. Gilead's drug was approved in December as a twice-yearly treatment for patients with multi-drug resistant HIV. The two companies decided to slam the brakes on the trial back in November 2021 after dosing was stopped in a related study testing a combo of islatravir and another drug called MK-8507. At the time, Merck disclosed that the islatravir-MK-8507 combo spurred a reduction in patients’ lymphocyte and CD4+ T-cell levels. But now islatravir is being revived, with an FDA hold on the trial having been lifted after an amended protocol using a lower dose of islatravir was agreed to, according to a Merck spokesperson. In addition, the company is launching multiple new phase 3 studies testing the med with its FDA-approved HIV drug Pifeltro. “We are committed to advancing the science to offer new treatment options for the treatment of HIV,” Dean Li, M.D., Ph.D., president of Merck Research Labs, said on the call. But elsewhere the company is reevaluating priorities. A spokesperson confirmed to Fierce Biotech that MK-7075, a treatment for overgrowth syndrome that did not appear in the company's earnings presentation, is "not currently active." The med is still in development but is being deprioritized, the spokesperson explained. The mid-stage pipeline updates come as Merck’s executives touted internal and external victories meant to assure investors that its post-Keytruda plans were materializing. Less than two weeks ago, the company announced it was buying Prometheus Biosciences for $10.8 billion, an immunology company with a promising lead asset developed to treat ulcerative colitis and Crone’s disease that recently posted a phase 2 victory. That med, PRA023, is set to do battle with a competitor from Roivant that's so far performed similarly. The deal echoes Merck’s $11.5 billion acquisition of Acceleron Pharma in September 2021, which handed the New Jersey pharma keys to cardiovascular med sotatercept, now a potential crown jewel. After diving deeper into the med’s phase 3 victory, Merck executives said today that they plan to file for U.S. approval in the third quarter for patients with pulmonary arterial hypertension. Chief Medical Officer Eliav Barr, M.D., previously told Fierce Biotech that he expects the drug to launch in early 2024. The sum of the Big Pharma’s recent deals and internal development had CEO Rob Davis sounding confident that Merck is well-situated to thrive beyond Keytruda’s expected loss of exclusivity in 2028. “I am no longer focusing on 2028,” he said on the call. “I am looking at 'how do we have sustainable growth well into the next decade.'"

临床2期并购临床3期上市批准

2022-10-26

·BiG生物创新社

金坚团队：首个靶向AKT变构位点的PROTAC

西奈山伊坎医学院金坚教授团队长期深耕于靶向蛋白降解领域，致力于蛋白降解药物的设计与开发，以及推进这些技术的临床应用与转化。该团队已经成功开发了多种靶点的PROTAC，克服了传统小分子药物的种种缺陷，为靶向蛋白降解领域的研发不断注入强心剂。包括：组蛋白甲基转移酶NSD家族NSD2/3，激酶家族AKT和ALK，EGFR以及表观遗传家族靶点EZH2等。此外，金坚教授团队也开发了其他新型PROTAC技术：1、叶酸笼罩的Folate-Caged PROTACs，该类PROTAC进一步提高了PROTAC的细胞选择性。2、基于寡核苷酸链的TF-PROTACs，成功实现了对不可成药转录因子的降解。3、光诱导PROTACopto-PROTAC，实现了PROTAC的可控激活。4、靶向WDR5 和Ikaros的双靶点PROTAC5、开发新型的E3连接酶KEAP1配体，并成功用于BRD3/4的降解。进一步拓展了靶向蛋白质降解的有限工具箱。前言AKT是癌症治疗的一个重要靶点。近年来，在开发ATP竞争性的活性位点和变构位点的AKT抑制剂方面取得了重大进展，多款AKT小分子抑制剂获批临床。此外，研究人员也开发了多种基于AKT活性位点的PROTAC，包括MS21。MS21可以有效诱导PI3K/pten通路突变的肿瘤细胞中AKT的降解，并有效抑制肿瘤细胞增殖生长，但在KRAS/BRAF突变细胞中却显得束手无策，无法降解AKT蛋白。近日，西奈山伊坎医学院金坚教授团队和Ramon E. Parsons团队在知名药物化学期刊JMC上发表题为“Novel Allosteric Inhibitor-Derived AKT Proteolysis Targeting Chimeras (PROTACs) Enable Potent and Selective AKT Degradation in KRAS/BRAF Mutant Cells”的文章。作者开发了首个基于变构位点的新型AKT PROTAC 62，并且化合物62在KRAS/BRAF突变的癌细胞以及PI3k/pten突变的癌细胞中均显示出强效的AKT降解活性和抗增殖活性。此外，62在通过腹腔内给药的小鼠体内表现出良好的生物利用度和PK性质。作者 | 缪可研AKT靶点介绍AKT（蛋白激酶b）是一种丝氨酸/苏氨酸激酶，属于丝氨酸蛋白激酶家族。AKT作为人类癌症中最常见的PI3K/AKT/m-TOR信号级联的中心节点，在调节癌症特征中发挥关键作用，如细胞增殖、代谢、转移、侵袭性和肿瘤细胞的存活（图1）。AKT由三个高度同源的亚型组成，AKT1/2/3，它们都有三个进化上保守的结构域：一个N端PH结构域，一个中心激酶催化结构域和一个C端调控结构域。研究表明，AKT的过度活化和过表达与许多总体预后较差的人类癌症有关。图1.AKT介导的信号通路AKT小分子抑制剂研究进展AKT是一种极具临床潜力的药物靶点。在过去数十年来，基于AKT领域的药物研发已经取得了积极的研究成果，多款AKT小分子抑制剂相继获批临床，包括靶向AKT活性位点的小分子抑制剂：GSK690693、GDC-0068、AZD5363和靶向AKT变构位点的抑制剂：MK-2206、ARQ-092、TAS-117。进展最快的是罗氏的GDC-0068和阿斯利康的AZD5363，目前均处于临床三期。然而，基于活性位点的AKT抑制剂具有严重的副作用，包括高血糖、血小板减少和感染，而AKT变构抑制剂在人体临床试验中也表现出有限的疗效。图2.进入临床试验的AKT小分子抑制剂已报道的基于活性位点抑制剂的AKT PROTAC基于靶向蛋白水解嵌合体PROTAC或分子胶的靶向蛋白降解技术（TPD）是一种通过降解致病靶蛋白来治疗疾病的治疗策略。通常，由PROTAC或分子胶诱导的泛素−蛋白酶体系统（UPS）介导的降解可以同时靶向癌蛋白的催化和非催化结构域，这可能产生比小分子激酶抑制剂更大的疗效。近年来，研究人员已经开发了多种靶向活性位点的AKT PROTAC（图3），其中，MS21是已报道最有效的AKT降解剂，然而MS21不能有效诱导携带KRAS或BRAF突变的癌细胞中AKT的降解。为了克服MS21等靶向活性位点PROTAC在携带KRAS/BRAF突变的癌细胞较差的降解AKT能力。作者另辟蹊径，试图从AKT的变构抑制剂切入，开发新型的靶向变构位点的AKT降解剂。图3.已报道的靶向活性位点的AKT PROTAC下面让我们一起走进这篇文献：1. 基于ARQ-092 PROTAC的设计思路及合成研究表明，与ATP竞争性结合的AKT活性位点抑制剂优先结合激活的AKT（磷酸化的AKT，p-AKT）。由于在KRAS/BRAF突变的肿瘤细胞系中，磷酸化AKT蛋白水平较低，这就影响了与ATP竞争性结合的活性位点抑制剂的效果，从而导致耐药。与靶向活性位点抑制剂不同，AKT变构抑制剂可以结合并稳定AKT的失活形式。因此，靶向AKT变构位点的PROTAC有可能在含有KRAS/BRAF突变的癌细胞中参与结合失活的AKT，这就可能诱导MS21耐药肿瘤细胞系中AKT的降解。首先，作者选取了AKT变构抑制剂ARQ-092作为AKT PROTAC的靶头化合物，随后通过对ARQ-092与AKT1的晶体复合物进行分析，作者发现ARQ-092中的左侧苯环伸向溶剂区（图4）。因此，作者选用该位点作为连接位点进行衍生化，分别合成了末端是羧基和氨基的化合物1（末端羧基）和2（末端氨基）。随后，作者基于化合物1和2开展PROTAC合成工作。图4. ARQ-092与AKT1的晶体复合物及化合物1和2的化学结构VHL配体VHL-1和CRBN配体泊马度胺是最常用的两种E3泛素连接酶配体。作者同时采用这两种E3配体，分别合成了基于VHL配体和CRBN配体两种类型的AKT PROTAC。最先开展的是基于化合物1（末端羧基）的PROTAC合成（图5）。其中，化合物3-20是基于VHL配体的PROTAC，作者分别合成了不同长度的聚乙二醇和烷烃链两种类型PROTAC。同时作者也合成了基于泊马度胺的PROTAC 21-32，同样采用了不同长度的聚乙二醇和烷烃链两种连接链类型。图5.基于化合物1的AKT PROTAC接下来，作者合成了基于化合物2（末端氨基）PROTAC 33-61（图6）。其中，化合物33-49是基于VHL配体的PROTAC，化合物50-61是基于泊马度胺的PROTAC。并且作者同样也考察了不同长度的聚乙二醇和烷烃链的连接链类型，其中化合物33-41和57-61是聚乙二醇类型的PROTAC，化合物42-49和50-56是烷烃链类型的PROTAC。图6.基于化合物2的AKT PROTAC2. PROTAC蛋白降解能力初筛实验接下来，作者在PC3细胞系（人前列腺癌细胞）上筛选合成的PROTAC 3-61对AKT蛋白的降解能力（图7）。蛋白降解实验表明基于VHL配体的PROTAC比基于泊马度胺的PROTAC具有更强的降解能力，且烷烃链比聚乙二醇链更有效。作者从构效关系研究发现了PROTAC 20、48和49具有较强的AKT降解能力，并可以有效抑制下游信号传导，如：p-akt、p-pras40和p-s6。图7. 化合物3-61的蛋白降解实验3. 基于最优化合物20的进一步结构优化及后续生物活性研究有研究表明，VHL-2（VHL-1中苄位甲基取代的结构）对VHL具有更高的亲和力。因此，作者选用了降解活性最好的PROTAC 20进行进一步结构改造，将20中的VHL-1替换成具有更高亲和力的VHL-2，得到了PROTAC 62。作者也分别合成了化合物63和64作为阴性对照化合物（图8）。图8. PROTAC 62及阴性对照63和64的化学结构首先，作者分别测试了PROTAC 62、63、64及靶头化合物ARQ-092对AKT三种不同亚型（AKT1、AKT2、AKT3）的酶抑制活性（图9）。实验结果显示，相较于靶头化合物ARQ-092，PROTAC表现出减弱的抑制活性，但对于AKT1/2/3都具有抑制活性。图9. PROTAC 62、63、64及ARQ-092的酶活测试接下来，作者测试了PROTAC 62、63、64在MS21（已报道的降解活性最好的靶向活性位点PROTAC）耐药且KRAS突变的结直肠癌细胞系SW620的降解活性（图10）。实验结果表明，化合物62能够呈现浓度依赖方式有效诱导SW620中的AKT降解，且DC50为23±16 nM，而阴性对照63和64无降解活性。图10.化合物62在sw620中的降解实验随后，作者比较了62和MS21在其他几种携带KRAS或BRAF突变的癌细胞类型中的AKT降解效应（图11）。蛋白质印迹实验发现，化合物62可以有效诱导各种KRAS或BRAF突变的癌细胞中AKT的降解，而MS21表现出较差的AKT降解能力。图11. 62和MS21在各种携带KRAS或BRAF突变的癌细胞蛋白降解实验作者继续在SW620细胞系进行了蛋白降解机制研究（图12），实验结果表明化合物62可以以时间依赖的方式诱导AKT降解，并可以有效抑制磷酸化PRAS40蛋白水平。当加入NAE抑制剂MLN4924或蛋白酶体抑制剂MG132后，可以有效逆转AKT的降解效果。基于上述实验结果，作者认为化合物62诱导AKT蛋白的降解效果依赖于泛素蛋白酶体途径。图12. 蛋白降解机制研究实验为了探究PROTAC 62蛋白质组范围内的降解选择性，作者对化合物62进行了基于全局串联质谱标签TMT定量蛋白分析的蛋白质组学研究，实验结果表明化合物62不能降解其他靶点蛋白，具有较好的靶点选择性（图13）。图13.化合物62的蛋白质组学研究接下来，作者在SW620细胞系上测试了化合物62、靶头化合物ARQ-092、阴性对照64及降解剂MS21的抗增殖活性（图14）。从细胞集落形成实验可以看出，化合物62对SW620抑制活性与ARQ-092相当，而阴性对照化合物64和MS21表现出较弱抑制活性。图14. 化合物62、64、ARQ-092、MS21的细胞集落形成实验最后，作者对化合物62进行了PK研究（图14），评估化合物62在小鼠体内的生物利用度。实验结果发现在给药后0.5 h可达到最大血药浓度（Cmax = 1 μM），血药浓度保持在100 nM以上至少可维持12小时。这些结果表明，化合物62表现出较好的PK性质，在体内可以获得足够的血浆暴露。图14. 化合物62在小鼠血浆浓度测试总结金坚课题组报道了首个靶向变构位点的AKT PROTAC 62，PRORAC 62能够有效诱导KRAS/BRAF突变肿瘤细胞的AKT降解，这可能为靶向活性位点的MS21耐药KRAS/BRAF突变癌症提供一个潜在的策略。同时，化合物62表现出较强的降解活性、较好的靶点选择性以及较好的PK性质，这是靶向AKT PROTAC领域的一大步，也是靶向AKT领域的药物研发的一大步。参考文献1、Novel Allosteric Inhibitor-Derived AKT Proteolysis TargetingChimeras (PROTACs) Enable Potent and Selective AKT Degradation in KRAS/BRAF Mutant Cells.2、Exploiting the PI3K/AKT pathway for cancer drug discovery. Nat. Rev. Drug Discovery 2005, 4 (12), 988−1004.3、Harnessing the E3 Ligase KEAP1 for Targeted Protein Degradation. DOI: 10.1021/jacs.1c04841. J. Am. Chem. Soc.2021, 143, 37, 15073–150834、4、TF-PROTACs Enable Targeted Degradation of Transcription Factors.J. Am. Chem. Soc.2021, 143, 23, 8902–8910. doi.org/10.1021/jacs.1c03852扫码加入BiG生物创新社读者交流群，分享、交流纯粹的行业知识，非诚勿扰！BiGScientific Driven, Making Impact!创新生态丨医药论坛丨行业分析媒体公关丨BiG Webinar联系我们商务：Max 18662346610媒体：Kathy 17621909690

蛋白降解靶向嵌合体小分子药物免疫疗法

100 项与 Miransertib 相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
D11409	-	-	DB14982

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
生长障碍	临床2期	西班牙	Merck GmbH	2019-09-19
Proteus综合征	临床2期	西班牙	-	2019-09-17
PIK3CA相关的过度生长现象	临床2期	西班牙	-	2017-05-16
子宫内膜癌	临床1期	美国	ArQule, Inc.	2015-06-09
子宫内膜癌	临床1期	美国	-	2015-06-09
卵巢癌	临床1期	美国	ArQule, Inc.	2015-06-09
卵巢癌	临床1期	美国	-	2015-06-09
淋巴瘤	临床1期	美国	ArQule, Inc.	2011-11-01
先天性心脏缺损	临床前	美国	Merck GmbH	-
血管闭塞危机	临床前	美国	Merck GmbH	-

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临床结果

适应症

分期

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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


NCT03094832 (CTgov)	临床1/2期	Proteus综合征 \| PIK3CA相关的过度生长现象	50	Miransertib (Part A: Miransertib PROS/PS)	繭淵艱襯膚鏇鹹衊夢願(製顧壓範積製醖齋簾餘) = 襯齋憲鹽夢遞鏇醖衊憲壓憲網選願築構膚壓選 (壓獵鹽鹽網顧齋憲獵窪, 艱鏇襯襯鹹壓齋繭糧醖 ~ 鑰簾襯鬱願艱簾築醖鑰) 更多	-	2023-03-31
NCT03094832 (CTgov)	临床1/2期	Proteus综合征 \| PIK3CA相关的过度生长现象	50	Miransertib (Part B: Miransertib PROS (Cohort 1))	繭淵艱襯膚鏇鹹衊夢願(製顧壓範積製醖齋簾餘) = 襯窪憲廠鏇鬱夢窪艱鬱壓憲網選願築構膚壓選 (壓獵鹽鹽網顧齋憲獵窪, 齋網觸淵齋範襯窪艱衊 ~ 夢繭衊顧獵鑰構製餘鹽) 更多	-	2023-03-31
NCT03094832 (MOSAIC, Biospace) 人工标引	临床1/2期	PIK3CA相关的过度生长现象 \| Proteus综合征	-	Miransertib	鑰餘齋獵簾壓艱積廠構(選憲襯齋糧廠製顧窪積) = mostly Grade 1 or 2 AEs 膚襯淵顧淵鏇製構艱襯 (糧鏇鬱範齋齋蓋築淵築 ) 更多	积极	2019-06-17
NCT02594215 (Pubmed \| Adv Exp Med Biol) 人工标引	N/A	Proteus综合征	6	Miransertib	廠餘壓遞顧製簾獵簾顧(鏇構構選蓋積觸膚鹽艱) = 50% reduction (5/6) 憲襯遞觸艱顧襯糧選願 (齋製鬱壓壓窪築簾遞選 )	积极	2019-03-07
NCT02476955 (ASCO2017) 人工标引	临床1期	实体瘤	13	carboplatin+paclitaxel+ARQ 092	鹽遞窪觸膚廠淵壓製獵(醖廠獵壓糧選夢獵艱範) = diarrhea 69%, fatigue 54%, hyperglycemia 31%, maculopapular rash 31%, nausea 23%, mucosal inflammation 23%, anemia 15%, platelet count decreased 15% and hypokalemia 15% 顧獵鏇製觸鏇獵獵願艱 (艱夢醖簾獵齋襯鬱憲繭 ) 更多	积极	2017-06-05
AACR2013	临床1期	HR阳性/HER2低表达实体瘤	22	ARQ 092	範艱鬱願築獵簾醖壓襯(鹽願鑰憲廠簾積簾範膚) = 艱餘範餘齋齋醖蓋觸衊廠顧襯艱鹽壓鏇網製鏇 (壓顧鏇積壓繭製窪鹽範 )	-	2013-04-15