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更新于：2025-03-04

Rocilinostat

更新于：2025-03-04

概要

概要

基本信息

药物类型

小分子化药

别名

Ricolinostat、ACY-1215、ACY-63

靶点

HDAC6

作用机制

HDAC6抑制剂(组蛋白去乙酰化酶-6抑制剂)

治疗领域

神经系统疾病内分泌与代谢疾病肿瘤+ [3]

在研适应症

糖尿病周围神经病变乳腺癌神经炎+ [1]

非在研适应症

腓骨肌萎缩症霍奇金淋巴瘤套细胞淋巴瘤+ [8]

原研机构

Celgene Corp.

在研机构

Acetylon Pharmaceuticals, Inc.北京本草瑞生医药科技香港有限公司

Regenacy Pharmaceuticals LLC初创企业

非在研机构

Celgene Corp.

最高研发阶段临床2期

首次获批日期-

最高研发阶段(中国)临床1期

特殊审评-

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结构/序列

分子式C24H27N5O3

InChIKeyQGZYDVAGYRLSKP-UHFFFAOYSA-N

CAS号1316214-52-4

关联

项与 Rocilinostat 相关的临床试验

CTR20220099

/ Completed临床1期

一项在乳腺癌患者中考察Ricolinostat治疗化疗诱导的周围神经病变（CIPN）的安全性、有效性和生物标志物作用的探索性研究

本研究的主要目的是评价 ricolinostat 在出现 CIPN 症状和体征的患者中的安全性和耐受性。探索性目的是评估 ricolinostat 治疗对 CIPN 临床表现和 IENFD 的作用。

开始日期2022-11-17

申办/合作机构

精鼎医药研究开发（上海）有限公司

[+2]

CTR20213336

/ Completed临床1期

一项开放、单次给药的I期临床研究，评价Ricolinostat在健康中国成年受试者中的安全性和药代动力学特征

主要目的：评价健康中国成年受试者单次口服120mg（10mg/mL）Ricolinostat后的安全性。次要目的：评价健康中国成年受试者单次口服Ricolinostat后原型药和代谢产物（ACY-344和ACY-349）的药代动力学特征。

开始日期2022-01-17

申办/合作机构

精鼎医药研究开发（上海）有限公司

[+2]

NCT05193851

/ Completed临床1期

A Phase I Clinical Study Evaluating the Safety and Pharmacokinetics of Ricolinostat in Chinese Subjects

This study is an open-label, phase I clinical study to evaluate the safety and pharmacokinetics of ricolinostat in healthy Chinese adult subjects.

开始日期2022-01-12

申办/合作机构-

100 项与 Rocilinostat 相关的临床结果

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100 项与 Rocilinostat 相关的转化医学

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100 项与 Rocilinostat 相关的专利（医药）

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235

项与 Rocilinostat 相关的文献（医药）

2024-12-01·INTERNATIONAL IMMUNOPHARMACOLOGY

IDH1/MDH1 deacetylation promotes NETosis by regulating OPA1 and autophagy

Article

作者: Zhang, Xiaoya ; Wang, Yukun ; Guo, Jin ; Gong, Zuojiong ; Shi, Chunxia ; Zhang, Danmei

BACKGROUND:

As a heterogeneous and life-threatening disease, the pathogenesis of acute liver failure (ALF) is complex. Our previous study has shown that IDH1/MDH1 deacetylation promotes ALF by regulating NETosis (a novel mode of cell death). In this article, we explore the manners of IDH1/MDH1 deacetylation regulates NETosis.

METHODS:

In vitro experiments, the formation of NETs was detected by immunofluorescence staining and Western blotting. LC3 fluorescence staining was used to detect autophagosome formation. To observe mitochondrial morphology, cells were stained by Mito-Tracker Red. Western blotting was used to detect the levels of autophagy protein and mitochondrial dynamin. In vivo experiments, the ALF model in mouse was established with LPS/D-gal, and the formation of NETs was detected by immunofluorescence staining and Western blotting. The autophagy levels were detected by Western blotting in liver samples.

RESULTS:

In dHL-60 cells, Western blotting results showed that the expression of OPA1 was higher in the IDH1/MDH1 deacetylated group compared with the IDH1/MDH1 WT group. And histone deacetylase inhibitor 6 (HDAC6i, ACY1215) decreased the expression level of OPA1 in IDH1/MDH1 deacetylated group. IDH1/MDH1 deacetylation increased the expression levels of both LC3B-II and Beclin 1, while decreasing the expression level of P62. It was reversed by ACY1215. Combined with our previous experiments, IDH1/MDH1 deacetylation upregulated autophagy concomitant with the increased expression of the markers of NETs formation. In a mouse model of ALF, ACY1215 further decreased the expression levels of LC3B-II and Beclin 1, while increasing the expression level of P62 in IDH1/MDH1 deacetylated mice.

CONCLUSIONS:

IDH1/MDH1 deacetylation promoted NETosis by regulating autophagy and OPA1 in vitro. The regulation of neutrophil autophagy on NETosis during IDH1/MDH1 deacetylation might be masked in mice. ACY1215 might attenuate NETosis by regulating neutrophil autophagy, which alleviated ALF aggravated by IDH1/MDH1 deacetylation.

2024-10-30·BIOLOGICAL & PHARMACEUTICAL BULLETIN

ACY1215 Exerts Anti-inflammatory Effects by Inhibition of NF-κB and STAT3 Signaling Pathway to Repair Spinal Cord Injury

Article

作者: Ding, Zhenfei ; Zhang, Hui ; Wang, Xiaohe ; Gao, Weilu ; Dai, Ce ; Liu, Rui ; Yin, Zongsheng

Spinal cord injury (SCI), a public health problem caused by mechanical injury, leads to secondary excessive inflammatory reactions and long-term damage to neurological function. ACY1215 is a highly selective histone deacetylase 6 (HDAC6) inhibitor and reportedly has anti-inflammatory effects; however, its regulatory role in SCI has not been studied. The purpose of this study was to explore the role of ACY1215 in preventing inflammation, inhibiting astrogliosis, enhancing remyelination and preserving axons after spinal cord injury and further exploring the possible cellular signaling pathways involved. First, lipopolysaccharide (LPS) was utilized to stimulate rat astrocytes in vitro. Quantitative RT (qRT)-PCR and Western blotting showed that ACY1215 inhibited the expression of glial fibrillary acidic protein (GFAP), interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-α (TNFα) in LPS-activated astrocytes. In addition, Western blotting results showed that ACY1215 could inhibit the signal transduction pathway of nuclear factor-κB (NF-κB) and signal transducer and activator of transcription 3 (STAT3). In vivo, ACY1215 could exert anti-inflammatory effects by inhibiting the expression of inflammatory cytokines, including IL-1β, IL-6, and TNF-α. Moreover, ACY1215 repaired spinal cord injury by reducing the formation of glial scars and promoting remyelination and nerve recovery. In summary, ACY1215 can inhibit the NF-κB and STAT3 signaling pathways in astrocytes, reduce inflammation and ameliorate SCI. Our results provide a novel strategy for the treatment of SCI.

2024-10-01·EXPERIMENTAL NEUROLOGY

ClassIIb histone deacetylase participates in perioperative neurocognitive disorders in elderly mice via HSP90/GR signaling pathway

Article

作者: Jin, Qiqi ; Wang, Jiao ; Li, Jun ; Liu, Yu ; Nivar, John ; Wang, Xinlin ; Cao, Hong ; Pan, Chi ; Cai, Weicha ; Tao, Yuanxiang

OBJECTIVE:

Multiple factors contribute to the development of perioperative neurocognitive disorders (PND). This study was designed to investigate whether Histone Deacetylase 6 (HDAC6) was involved in the formation of postoperative cognitive dysfunction in elderly mice by regulating the degree of acetylation of heat shock protein (HSP90) and related protein functions and quantities.

METHODS:

C57BL/6 J male mice were randomly divided into six groups: control naive (group Control), anesthesia (group Anesthesia), splenectomy surgery (group Surgery), splenectomy surgery plus dissolvent (group Vehicles), splenectomy surgery plus the inhibitor ACY-1215 (group Ricolinostat), and splenectomy surgery plus the inhibitor RU-486(group Mifepristone). After the mice were trained for Morris Water Maze (MWM) test for five days, anesthesia and operational surgery were carried out the following day. Cognitive function was assessed on the 1st, 3rd and 7th days post-surgery. The hippocampi were harvested on days 1, 3, and 7 post-surgeries for Western blots and ELISA assays.

RESULTS:

Mice with the splenectomy surgery displayed the activation of the hypothalamic-pituitary-adrenal axis (HPA-axis), marked an increase in adrenocorticotropic hormone (ACTH), glucocorticoid, mineralocorticoid at the molecular level and impaired spatial memory in the MWM test. The hippocampus of surgical groups showed a decrease in acetylated HSP90, a rise in glucocorticoid receptor (GR)-HSP90 association, and an increase in GR phosphorylation and translocation. HDAC6 was increased after the surgical treated. Using two specific inhibitors, HDAC6 inhibitor Ricolinostat (ACY-1215) and GR inhibitor Mifepristone (RU-486), can partially mitigate the effects caused by surgical operation.

CONCLUSIONS:

Abdominal surgery may impair hippocampal spatial memory, possibly through the HDAC6-triggered increase in the function of HSP90, consequently strengthening the negative role of steroids in cognitive function. Targeting HDAC6- HSP90/GR signaling may provide a potential avenue for the treatment of the impairment of cognitive function after surgery.

项与 Rocilinostat 相关的新闻（医药）

2022-09-28

·BioSpace

Portfolio Highlights: Clinical and Financial Updates of ABM, F5, AceLink, HAYA, Regenacy, and Arthrosi

SHANGHAI, Sept. 28, 2022 /PRNewswire/ -- As the investment division of Viva Biotech, Viva BioInnovator is committed to being a collaborative platform for Innovative Biotech companies from around the world. Over the past 2 months, our portfolio companies progressed greatly. ABM Therapeutics Announces First Patient Dosed in Phase I Clinical Trial of ABM-1310 in China On September 16, 2022, ABM Therapeutics, a clinical-stage biopharmaceutical company that is invested and incubated by Viva BioInnovator, announced that the first patient has been successfully dosed with ABM-1310 in a multi-center phase I clinical trial in China. ABM-1310, ABM Therapeutic's proprietary clinical candidate developed as a next-generation BRAF inhibitor, is a highly selective, highly water-soluble, orally administrated, and brain-penetrant small molecule BRAF inhibitor. ABM-1310 phase I trial, conducted in China, is a multi-center, open-label study to investigate the safety, tolerability, pharmacokinetics, and preliminary anti-tumor activity of ABM-1310 in Chinese patients with BRAF V600X mutated advanced solid tumors. F5 Therapeutics awarded First Servier FAST Discovery Award F5 Therapeutics, which invested and incubated by Viva BioInnovator, was recently awarded the first Servier FAST Discovery Award. Winning this award means F5 stood out from 23 applications, indicating the industry's recognition of F5's innovative treatment methods in the field of biomedicine. "Servier FAST Discovery Award" is co-sponsored by Servier and the California Life Sciences Association (CLSA) to support early-stage life science companies using innovative approaches in areas designated by the group: oncology, auto-immune diseases, genetically driven neurodegenerative, and movement disorders. F5 is transforming targeted protein degradation to advance drug discovery by utilizing the cell's normal protein regulation systems to remove disease-causing proteins that cannot be targeted by traditional approaches. The NExMods™ Platform (NEosubstrate Expression Modulators) represents a novel approach to "molecular glues" capable of delivering effective medicines to patients across diverse therapeutic areas: oncology, immuno-oncology, fibrosis, inflammation, and neurodegeneration. AceLink Therapeutics Receives Orphan Drug Designation for its Novel GCS inhibitor AL01211 for the Treatment of Fabry Disease AceLink Therapeutics, Inc. (AceLink), invested and incubated by Viva BioInnovator, is an innovative biopharmaceutical company developing transformative therapies for genetic diseases. On September 7, 2022, they announced that they received Orphan Drug Designation (ODD) from the U.S. Food and Drug Administration (FDA) for AL01211 as a treatment for Fabry Disease. AL01211 was selected based on its unique properties to effectively treat peripheral organs that Fabry disease affects by reducing the risk of off-target effects by preventing the crossing of the blood-brain barrier. HAYA Therapeutics won the "TOP 100 Swiss Startup Award 2022" and was successfully selected for the "Soonicorn Club 2022" On Sept. 7th, 2022, the "Top 100 Swiss Startup Award 2022," sponsored by Venturelab, was announced. HAYA Therapeutics, invested and incubated by Viva BioInnovator, was named TOP100 Swiss Startups' 8th Best Startup and came first in the Cardiovascular & Drug Discovery sectors. In addition, HAYA Therapeutics was recently included in the"SoonicornClub 2022", which names the top Swiss technology startups. The awards given demonstrate the industry's recognition of their potential in the field of biomedicine. Regenacy Pharmaceuticals Announces Completion of Enrollment for their Phase 2 Study in Diabetic Peripheral Neuropathy and $9.3 Million in Series B Financing Regenacy Pharmaceuticals Inc, invested and incubated by Viva BioInnovator, is a clinical-stage, biopharmaceutical company developing breakthrough treatments for diabetes and other peripheral neuropathies. On August 24, 2022, they announced completion of enrollment for the company's phase 2 study of ricolinostat, an oral selective deacetylase 6 (HDAC6) inhibitor for painful diabetic peripheral neuropathy (DPN). The company also announced the closing of a $9.3 million Series B financing led by Cobro Ventures. Arthrosi Completes AR882 Renal Impairment Study and its Phase 2b Study Enrollment Arthrosi Therapeutics, Inc., which invested and incubated by Viva BioInnovator, is a clinical-stage biotechnology company focused on the treatment and management of gout. On August 9, 2022, they announced the completion of their renal impairment study that utilizes the lead compound, AR882. AR882 is a potent and selective uricosuric agent which has shown effectiveness in lowering serum urate in patients with normal renal function and in patients with mild to severe renal impairment. On Aug. 23, 2022, Arthrosi announced the completion of enrollment for its global Phase 2b clinical study of AR882 for the treatment of chronic gout. The study, which exceeded the initial target enrollment of 120 patients, is designed to evaluate the safety and efficacy of AR882 in chronic gout patients who meet ACR/EULAR gout classification. About ABM Therapeutics ABM Therapeutics, a clinical-stage biopharmaceutical company with a mission to focus on the small molecule research and development of novel drugs for the treatment of cancer, and on brain cancer and cancer metastases. ABM has been building its broad and robust proprietary pipeline to construct a brain medicine R&D platform through collaboration with CROs. ABM's pipeline includes several programs in various stages of discovery and development, most of which have improved brain permeability to address the unmet needs of treating cancers and metastases in the brain. About F5 Therapeutics F5 is evolving targeted protein degradation to transform the landscape of drug discovery by utilizing the cell's normal protein regulation systems to remove disease causing proteins that cannot be targeted by traditional approaches. The NExMods™ Platform (NEosubstrate Expression Modulators) represents a novel approach to "molecular glues" capable of delivering impactful medicines to patients across diverse therapeutic areas: oncology, immuno-oncology, fibrosis, inflammation, and neurodegeneration. About AceLink Therapeutics Founded in 2018, AceLink Therapeutics is an innovative biopharma startup focusing on developing safe and effective medicines to address genetic diseases with high unmet needs. The company's initial focus is to develop novel therapeutics for Fabry disease. For more information, please visit . About HAYA Therapeutics HAYA Therapeutics is a precision therapeutics company that discovers and develops innovative tissue- and cell-selective genomic medicines for fibrotic diseases and other serious health conditions associated with aging, including cancer. The company's discovery engine focuses on long non-coding RNAs (lncRNAs) within the "dark matter" of the human genome -- key tissue and cell-specific drivers of fibrosis and other disease processes -- to identify novel targets and drug candidates with the potential for greater efficacy and safety than existing treatments. About Regenacy Regenacy Pharmaceuticals, Inc. is a clinical-stage biopharmaceutical company regenerating biological function by protein acetylation for the treatment of diabetic and other peripheral neuropathies and other chronic conditions. The company's selective inhibition technology provides superior safety profiles and potential enhanced efficacy compared to non-selective HDAC inhibitors. Regenacy selectively inhibits histone deacetylase 6 (HDAC6) to restore normal intracellular protein and organelle transport in peripheral neuropathies, and also has a portfolio of selective HDACs 1 and 2 inhibitors that have potential to treat major blood diseases such as leukemia, sickle cell disease, β-thalassemia, and cognitive dysfunction in neurological disorders. About Arthrosi Therapeutics Arthrosi Therapeutics, Inc. was founded in San Diego, CA, in 2018 with a mission to create a revolutionary treatment option to target uric acid levels and reduce joint damage for people living with gout. With its vast therapeutic and treatment knowledge, Arthrosi has accumulated a comprehensive and robust intellectual property portfolio and impressive Phase I and Phase II data showing industry leading efficacy rates and superior safety pro To learn more about Arthrosi, please visit View original content: SOURCE Viva Biotech Holdings

合作孤儿药小分子药物

2022-08-25

·BioSpace

Regenacy Pharmaceuticals Announces Completion of Enrollment for Phase 2 Study in Diabetic Peripheral Neuropathy & $9.3 Million Series B Financing

WALTHAM, Mass.--(BUSINESS WIRE)-- Regenacy Pharmaceuticals Inc, a clinical-stage biopharmaceutical company developing breakthrough treatments for diabetic and other peripheral neuropathies, announced completion of enrollment of the company’s phase 2 study of ricolinostat, an oral selective histone deacetylase 6 (HDAC6) inhibitor, in painful diabetic peripheral neuropathy (DPN). The company also announced the closing of a $9.3 million Series B financing led by Cobro Ventures with participation from Taiwania Capital Management Corporation, 3E Bioventures Capital, Yonjin Venture, and other undisclosed private investors. Painful DPN is characterized by debilitating symptoms that include pain, aberrant sensation, and loss of motor and sensory function. There is an important medical need for new treatments since available therapies do not address the full spectrum of signs and symptoms and offer only limited relief for many patients. Ricolinostat, and other HDAC6 inhibitors, have shown efficacy in animal models of DPN, chemotherapy-induced peripheral neuropathy (CIPN) and Type 2 Charcot Marie Tooth (CMT) disease, and have demonstrated a promising safety and tolerability profile. The ongoing double-blinded placebo-controlled clinical study, which recently completed enrollment, assesses the efficacy of ricolinostat in patients with painful DPN and other neuropathic symptoms. Initial results are expected to be available later this year. Regenacy plans to use the additional financing from this Series B to continue advancing the ricolinostat clinical development program. “Regenacy is committed to exploring ricolinostat’s unique and differentiating potential to address the underlying pathophysiology of small fiber neuropathies,” said David Michelson, M.D., Regenacy’s Chief Medical Officer. “The compelling data we have seen in preclinical studies indicate ricolinostat’s selective inhibition of HDAC6 may provide meaningful relief to patients suffering from painful DPN and other neuropathies, and we look forward to its continued progression in the clinic.” “We are energized by the ongoing support of our investors who share in our mission to address the underlying causes of peripheral neuropathy,” said John Rocha, Regenacy’s Chief Financial Officer. “This Series B positions Regenacy for continued progress as we uncover the potential of ricolinostat to restore peripheral nerve function.” “We at Regenacy believe that ricolinostat shows first-in-class potential to go beyond symptomatic treatment and instill lasting disease-modifying effects for patients with peripheral neuropathies,” said Simon Jones, Ph.D., Regenacy’s President and Chief Executive Officer. “This Series B financing comes at a pivotal stage in our clinical development, as we continue to evaluate ricolinostat in painful diabetic peripheral neuropathy while simultaneously advancing our joint venture Beijing 3E-Regenacy Pharmaceuticals Co., Ltd. to investigate ricolinostat in patients with chemotherapy-induced peripheral neuropathy (CIPN) in China.” Concurrent with the financing, Todd Kaloudis, Managing Director at Cobro Ventures, has joined Regenacy’s Board of Directors. Additionally, Regenacy announced the appointment of William W. Chin, M.D., SVP of Clinical and Translational Science at Frequency Therapeutics, as Executive Chairman of the Board and Michael Huang, Managing Partner at Taiwania Capital, as Vice-Chairman, effective immediately. Mr. Huang has served on Regenacy’s Board since 2020, and Dr. Chin has served since 2018 and is Chairman of Regenacy’s Scientific Advisory Board. About Ricolinostat Ricolinostat, an oral, selective histone deacetylase 6 (HDAC6) inhibitor, has the potential to become the first-in-class treatment that reverses the underlying peripheral neuropathy, thereby relieving pain, numbness, motor function loss, and all other symptoms of the disease. Ricolinostat restores nerve function by inhibiting HDAC6, which reestablishes the transport function of microtubules in the axon of the nerve cell. A functioning microtubule transport system is the key to restoring nerve function because nerves rely on this network to supply the energy and nutrients necessary to maintain the nerve signaling in the ends of the nerves in the skin and muscles of the feet and hands. When this transport is disrupted by a disease like diabetes or neurotoxic drugs used in chemotherapy, nerve cells can malfunction and send random signals (pain, tingling, muscle spasms) or no signal at all (numbness, paralysis). Multiple preclinical animal models have demonstrated that HDAC6 inhibition restores nerve fibers, leading to the reversal of both pain and numbness in peripheral and other neuropathies, such as diabetic peripheral neuropathy (DPN), chemotherapy-induced peripheral neuropathy (CIPN) and Charcot-Marie-Tooth disease Type 2, an orphan-designated disease. About Regenacy Regenacy Pharmaceuticals, Inc. is a clinical-stage biopharmaceutical company regenerating biological function by protein acetylation for the treatment of diabetic and other peripheral neuropathies and other chronic conditions. The company’s selective inhibition technology provides superior safety profiles and potential enhanced efficacy compared to non-selective HDAC inhibitors. Regenacy selectively inhibits histone deacetylase 6 (HDAC6) to restore normal intracellular protein and organelle transport in peripheral neuropathies, and also has a portfolio of selective HDACs 1 and 2 inhibitors that have potential to treat major blood diseases such as leukemia, sickle cell disease, β-thalassemia, and cognitive dysfunction in neurological disorders.

First in Class

2022-08-05

·生物谷

Cell Stem Cell: 我国科学家在化学重编程获得巨核细胞及血小板研究领域取得重要突破

运用化学重编程技术实现了人成红细胞向巨核细胞及血小板的命运转换，并利用单细胞转录组和染色质开放性测序技术系统追踪了该过程中的细胞动态变化。血小板是由骨髓等造血组织中巨核细胞产生的具有生物活性的无核细胞，在机体止血、血栓形成、免疫调节、抗感染等生理和病理过程中发挥重要作用。临床上，血小板减少症常见于再生障碍性贫血、特发性血小板减少性紫癜等血液系统疾病。此外，病毒/细菌性感染、创伤、急性放射病、肿瘤放化疗等也易引发血小板减少。血小板输注是临床治疗血小板减少症、防治出血、挽救生命的主要手段之一。然而临床上血小板供应仅有健康志愿者捐献的唯一途径，而血小板贮存时间短且易被污染，遇到战争、重大自然灾害、突发公共卫生事件（如突发传染病）发生时，血小板短缺问题就会更加突出，因此亟需运用新技术解决血小板来源问题。基于干细胞技术、细胞重编程技术获取巨核细胞及血小板的研究一直是国际竞争的前沿与热点领域之一。体外仅通过化学小分子介导的重编程技术制备人巨核细胞（血小板的前体细胞）及血小板的研究成果鲜有报道。近日，军事医学研究院裴雪涛/李艳华团队联合天津大学医学部张健课题组运用化学重编程技术实现了人成红细胞向巨核细胞及血小板的命运转换，并利用单细胞转录组和染色质开放性测序技术系统追踪了该过程中的细胞动态变化。2022年8月4日，干细胞领域顶级期刊《Cell Stem Cell》（《细胞·干细胞》）在线发表了相关研究论文。在细胞重编程的研究中，种子细胞的选择对于能否成功而有效地启动细胞命运转换至关重要。前期研究表明，起始细胞和目的细胞在发育谱系上亲缘关系越近，越容易实现细胞类型转化。成红细胞是存在于骨髓、外周血和脐带血中的一种有核红细胞，成红细胞和巨核细胞在发育过程中来自共同的前体，即巨核-红系共祖细胞，它们之间紧密的谱系联系使成红细胞成为获得巨核细胞理想的候选种子细胞。研究人员通过从多个表观遗传调控和信号通路相关的小分子化合物中筛选出一个含有四个小分子的化合物组合，惊奇地发现该小分子化合物“鸡尾酒”能将人成红细胞高效地重编程为巨核细胞。研究人员进一步确定了两阶段的诱导及巨核细胞特化的体系，最终获得了与天然巨核细胞特性相似的诱导性巨核细胞（induced megakaryocytes, iMKs）。巨核细胞最重要的功能是能产生前血小板及血小板。研究人员首先通过体外实验分析iMKs是否具有生成血小板的能力。在体外特定诱导分化条件下，iMKs能够形成网状的具有多个分支延伸突起的前血小板并释放血小板。更为重要的是，研究人员发现iMKs来源的血小板表现出与天然血小板相似的凝血酶激活响应，并具有粘附、聚集等功能。为了确定iMKs是否具有体内生成功能性血小板的能力，研究人员将iMKs直接通过尾静脉注射到血小板减低症的免疫缺陷小鼠体内，他们在iMKs输注后的第1-3天检测到了人源性血小板，并通过微流控实验证实这些血小板具有参与血栓形成的能力。为了解析四个小分子“鸡尾酒”如何实现成红细胞向巨核细胞的谱系命运转变，研究人员运用单细胞测序技术、染色质开放性测序技术对重编程过程进行了系统追踪和深度剖析。他们发现起始细胞经历了一个红系/巨核共前体细胞的阶段，该阶段的细胞具有红细胞及巨核细胞的双向分化潜能。进一步分析发现，该化合物组合引发了广泛的染色质重塑变化，红系细胞发育关键性基因的染色质开放程度逐渐降低，造血及巨核发生相关的重要转录因子基因位点的染色质开放程度逐渐升高，从而逐渐启动了巨核细胞发育程序。值得注意的是，他们发现iMKs可以分为两个亚群，其中一个亚群为血小板生成偏向性强的巨核细胞，在iMKs总群体中的比例大于70%。另一个亚群是免疫偏向性的巨核系细胞，可能在免疫调节、炎症调节过程中发挥作用。四分子的重编程体系更有利于产生血小板生成偏向性强的巨核细胞。综上所述，该研究团队独辟蹊径，仅运用小分子化合物成功实现成红细胞向功能性巨核细胞及血小板的命运转变，为体外大规模人工制备巨核细胞和血小板开辟了新的路径。该化学重编程技术具有安全可控、高效便捷等优势，通过该技术获得的功能性巨核细胞及血小板有望为临床血小板短缺等问题的解决开辟全新的途径，在血液系统疾病、急性放射病、战创伤、病毒或细菌性传染病等多种疾病引发的血小板减少症、出血的防治等方面展现出潜在的临床应用价值。军事医学研究院裴雪涛研究员和李艳华研究员为该论文的共同通讯作者。军事医学研究院覃金华副研究员、天津大学医学部张健副教授以及军事医学研究院博士研究生姜佳楠是论文的并列第一作者。该研究得到国家重点研发计划和国家自然科学基金的支持和资助。

小分子药物

100 项与 Rocilinostat 相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
-	-	-	DB12376

研发状态

10 条进展最快的记录,

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适应症	最高研发状态	国家/地区	公司	日期
糖尿病周围神经病变	临床2期	美国	Regenacy Pharmaceuticals LLC初创企业	2020-12-07
霍奇金淋巴瘤	临床2期	美国	Acetylon Pharmaceuticals, Inc.	2014-04-02
套细胞淋巴瘤	临床2期	美国	Acetylon Pharmaceuticals, Inc.	2014-04-02
多发性骨髓瘤	临床2期	美国	Acetylon Pharmaceuticals, Inc.	2014-04-02
难治性非霍奇金淋巴瘤	临床2期	美国	Acetylon Pharmaceuticals, Inc.	2014-04-02
难治性多发性骨髓瘤	临床2期	美国	Celgene Corp.	2014-03-01
乳腺癌	临床1期	中国	北京本草瑞生医药科技香港有限公司	2022-11-17
神经炎	临床1期	中国	北京本草瑞生医药科技香港有限公司	2022-11-17
卵巢癌	临床1期	美国	Celgene Corp.	2016-06-15
原发性腹膜癌	临床1期	美国	Celgene Corp.	2016-06-15

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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


NCT03176472 (CTgov)	临床2期	糖尿病周围神经病变	282	ricolinostat (Ricolinostat)	餘窪窪鬱範繭艱遞獵積(觸遞淵鹽繭衊範衊積衊) = 蓋選艱網夢淵構鏇鹹膚獵廠網憲夢築鹹膚範築 (築觸遞顧廠觸艱願選選, 鏇蓋醖壓獵憲繭鹹鹽蓋 ~ 鹹鬱範襯蓋選糧製選壓) 更多	-	2023-09-21
NCT03176472 (CTgov)	临床2期	糖尿病周围神经病变	282	Placebo (Placebo)	餘窪窪鬱範繭艱遞獵積(觸遞淵鹽繭衊範衊積衊) = 構窪壓齋齋觸鑰顧鹹齋獵廠網憲夢築鹹膚範築 (築觸遞顧廠觸艱願選選, 夢範夢鏇鏇築築構鏇範 ~ 鬱鹽壓廠鹽遞鹹廠鬱繭) 更多	-	2023-09-21
AACR2020	临床1/2期	转移性乳腺癌	16	Ricolinostat 240 mg qd + nab-paclitaxel	廠鏇觸獵鹹鹽鏇遞選淵(簾鬱築鏇製鹹鹽壓蓋構) = 鹽顧衊範簾壓觸壓顧淵鑰築鑰繭繭鏇顧鏇構積 (觸願積觸艱憲選窪醖淵, 4.45 ~ 11.0)	积极	2020-08-15
NCT02661815 (CTgov)	临床1期	卵巢癌 \| 原发性腹膜癌 \| 复发性铂耐药性输卵管癌	6	paclitaxel+Ricolinostat (Phase 1 Escalation Cohort)	膚壓繭網鑰選艱憲憲衊(膚艱鑰憲遞窪膚窪遞願) = 繭醖窪構鑰齋鹹觸鏇獵鬱網襯襯鏇艱築淵簾淵 (膚齋憲選構廠獵憲艱壓, 製觸廠餘蓋衊積艱鑰繭 ~ 壓獵艱觸願鬱壓顧鬱鹹) 更多	-	2019-11-08
NCT02661815 (CTgov)	临床1期	卵巢癌 \| 原发性腹膜癌 \| 复发性铂耐药性输卵管癌	6	paclitaxel+Ricolinostat (Phase 1 Expansion Cohort A)	構鑰選築廠餘鏇願夢憲(鹽願餘積遞願遞範鑰鹹) = 鬱壓鏇顧鏇餘繭觸夢憲選獵繭衊鏇蓋壓膚鏇鑰 (蓋廠壓艱襯淵憲鬱網積, 繭遞廠憲選鹽遞範鏇窪 ~ 遞夢鑰衊艱鬱衊衊鬱獵) 更多	-	2019-11-08
NCT02661815 (Pubmed) 人工标引	临床1期	复发性卵巢癌 \| 铂类耐药性原发性腹膜癌 \| 输卵管癌二线	6	paclitaxel+ricolinostat	鹹獵築觸醖鹽觸窪壓醖(簾遞鹽襯製襯糧選觸憲) = 構願廠鹽願鬱觸簾製廠構簾網鏇築襯鏇壓願醖 (餘顧淵齋憲遞願選範鹹 ) 更多	积极	2019-08-10
NCT02632071 (ASCO 12018 \| ASCO 22018) 人工标引	临床1期	转移性乳腺癌	17	ACY-1215+nab-paclitaxel	製鹹觸鏇衊遞糧窪糧網(鏇齋蓋衊遞範鹹鏇夢積) = none 鏇觸構網衊簾廠餘遞糧 (觸積網憲窪憲網積繭醖 ) 更多	积极	2018-06-02
NCT01583283 (Pubmed \| Lancet Oncol) 人工标引	临床1期	多发性骨髓瘤	38	lenalidomide+dexamethasone+ricolinostat	齋壓廠膚齋淵鏇網鹹願(壓構壓夢膚繭鏇選膚顧) = icolinostat（160 mg once daily on days 1-21 of a 28 day cycle）+ lenalidomide（25 mg）+dexamethasone（40 mg）衊製願鬱憲壓壓製憲顧 (膚窪願鏇壓襯糧遞壓齋 ) 更多	积极	2016-11-01