Arginine Butyrate(Arginine Butyrate) - 药物靶点：thymidine kinase_在研适应症：短肠综合征_专利_临床

概要

基本信息

药物类型

小分子化药

别名

靶点

thymidine kinase

作用机制

thymidine kinase刺激剂(胸苷激酶刺激剂)

治疗领域

消化系统疾病内分泌与代谢疾病其他疾病

在研适应症

短肠综合征

非在研适应症

镰状细胞血症β地中海贫血爱泼斯坦-巴尔病毒阳性淋巴瘤+ [2]

原研机构

Boston University

在研机构

Baxter Healthcare Corp.

非在研机构

Boston UniversityHemaQuest Pharmaceuticals, Inc.

最高研发阶段临床前

首次获批日期-

最高研发阶段(中国)-

特殊审评孤儿药 (美国)

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结构/序列

分子式C10H22N4O4

InChIKeyHTWPXGKLFMPZHG-WCCKRBBISA-N

CAS号80407-72-3

关联

5

项与 Arginine Butyrate 相关的临床试验

NCT00992732

/ Terminated临床2期

A Phase 2a Open-Label Multi-Center Study Evaluating HQK-1004 Administered With Valganciclovir in Patients With Relapsed or Refractory Epstein-Barr Virus-Positive Lymphoid Malignancies or Lymphoproliferative Disorders

The purpose of this study is to determine if treatment with HQK-1004 and valganciclovir will result in complete or partial responses in patients with EBV-positive lymphoid malignancies or lymphoproliferative disorders.

开始日期2010-05-01

申办/合作机构

HemaQuest Pharmaceuticals, Inc.

NCT00917826

/ Terminated临床2期

A Phase II Trial of Low-Dose Arginine Butyrate and Ganciclovir/Valganciclovir in EBV(+)Lymphoid Malignancies

The purpose of this study is to assess whether administration of Arginine Butyrate + ganciclovir/valganciclovir for up to three 21-day cycles is tolerable, and results in partial or complete responses in patients with EBV(+) lymphoid malignancies.

开始日期2008-09-01

申办/合作机构

HemaQuest Pharmaceuticals, Inc.

[+1]

NCT00006136

/ Completed临床2期IIT

Phase II Study of Arginine Butyrate With or Without Epoetin Alfa in Patients With Thalassemia Intermedia

OBJECTIVES: I. Determine whether arginine butyrate with or without epoetin alfa can stimulate gamma-globin chain production to a degree that decreases anemia and results in hematologic improvement in patients with thalassemia intermedia.
II. Determine whether a proportional increase in gamma-globin synthesis and mRNA and an improvement in nonalfa and alfaglobin chain imbalance by at least 10% over baseline correlate with improved hematologic response in these patients when treated with this regimen.
III. Determine whether a decrease in hemolysis, as assayed by a decrease in LDH, compared to baseline levels correlates with improved hematologic response in these patients when treated with this regimen.
IV. Determine whether any particular genotypes are more responsive than others to this therapy in these patients.
V. Determine whether baseline epoetin alfa levels, gender, and/or baseline reticulocyte counts (or percent circulating nucleated erythroblasts) correlate with improved hematologic response in these patients when treated with this regimen.

开始日期1999-03-01

申办/合作机构

Boston University

100 项与 Arginine Butyrate 相关的临床结果

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100 项与 Arginine Butyrate 相关的转化医学

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100 项与 Arginine Butyrate 相关的专利（医药）

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52

项与 Arginine Butyrate 相关的文献（医药）

2025-06-01·Biomaterials

Bioresponsive nanoreactor initiates cascade reactions for tumor vascular normalization and lactate depletion to augment immunotherapy

Article

作者: Peng, Xinran ; Yu, Jiayin ; Chen, Jiaoyu ; Hong, Sheng ; Ding, Xin ; Bu, Changxin ; Yuan, Peiyan ; Lu, Yuting

Immune checkpoint blockade (ICB) therapy has revolutionized cancer treatment. However, abnormal tumor vasculature and excess lactate contribute to tumor immunosuppression and confer resistance to ICB therapy, seriously limiting its clinical application. Here, we have developed a bioresponsive nanoreactor, ALMn, which consists of hollow manganese dioxide nanoparticles with encapsulation of lactate oxidase and L-Arginine, to overcome immunosuppression and sensitize ICB therapy. In the tumor microenvironment, lactate oxidase catalyzes lactate to produce hydrogen peroxide, which subsequently oxidizes L-Arginine to generate nitric oxide for vascular normalization. Through cascade reactions, ALMn effectively depletes excess lactate and normalize tumor vasculature, reshaping the immunosuppressive phenotype to an immune-activated one. Transcriptomics and immunological analyses prove that ALMn facilitates the infiltration and activation of effector cells, further potentiating antitumor immunity. Consequently, ALMn sensitizes anti-PD-L1 therapy, significantly suppressing tumor growth with an 83.7 % suppression, and prolonging the survival of mice, with the median survival time increasing from 29.5 days to 54.5 days. Our study demonstrates that ALMn effectively alleviates tumor immunosuppression and synergizes with anti-PD-L1, which shows promise in boosting ICB therapy.

2022-09-01·Molecular Diagnosis & Therapy

Targeting Genetic Modifiers of HBG Gene Expression in Sickle Cell Disease: The miRNA Option

Review

作者: Gu, Qingqing ; Pace, Betty S ; Starlard-Davenport, Athena

Sickle cell disease (SCD) is one of the most common inherited hemoglobinopathy disorders that affects millions of people worldwide. Reactivation of HBG (HBG1, HBG2) gene expression and induction of fetal hemoglobin (HbF) is an important therapeutic strategy for ameliorating the clinical symptoms and severity of SCD. Hydroxyurea is the only US FDA-approved drug with proven efficacy to induce HbF in SCD patients, yet serious complications have been associated with its use. Over the last three decades, numerous additional pharmacological agents that reactivate HBG transcription in vitro have been investigated, but few have proceeded to FDA approval, with the exception of arginine butyrate and decitabine; however, neither drug met the requirements for routine clinical use due to difficulties with oral delivery and inability to achieve therapeutic levels. Thus, novel approaches that produce sufficient efficacy, specificity, and sustainable HbF induction with low adverse effects are desirable. More recently, microRNAs (miRNAs) have gained attention for their diagnostic and therapeutic potential to treat various diseases ranging from cancer to Alzheimer's disease via targeting oncogenes and their gene products. Thus, it is plausible that miRNAs that target HBG regulatory genes may be useful for inducing HbF as a treatment for SCD. Our laboratory and others have documented the association of miRNAs with HBG activation or suppression via silencing transcriptional repressors and activators, respectively, of HBG expression. Herein, we review progress made in understanding molecular mechanisms of miRNA-mediated HBG regulation and discuss the extent to which molecular targets of HBG might be suitable prospects for development of SCD clinical therapy. Lastly, we discuss challenges with the application of miRNA delivery in vivo and provide potential strategies for overcoming barriers in the future.

2014-11-01·Neurobiology of Disease2区 · 医学

Arginine butyrate per os protects mdx mice against cardiomyopathy, kyphosis and changes in axonal excitability

2区 · 医学

Article

作者: Roulot, Morgane ; Sebrié, Catherine ; Herbin, Marc ; Benoit, Evelyne ; Fromes, Yves ; Vianello, Sara ; Boerio, Delphine ; de la Porte, Sabine ; Bouyon, Sophie

Duchenne muscular dystrophy (DMD) is a progressive neuromuscular disease caused by lack of dystrophin, a sub-sarcolemmal protein, which leads to dramatic muscle deterioration. We studied in mdx mice, the effects of oral administration of arginine butyrate (AB), a compound currently used for the treatment of sickle cell anemia in children, on cardiomyopathy, vertebral column deformation and electromyographic abnormalities. Monthly follow-up by echocardiography from the 8th month to the 14th month showed that AB treatment protected the mdx mice against drastic reduction (20-23%) of ejection fraction and fractional shortening, and also against the ≈20% ventricular dilatation and 25% cardiac hypertrophy observed in saline-treated mdx mice. The phenotypic improvement was corroborated by the decrease in serum CK level and by better fatigue resistance. Moreover, AB treatment protected against the progressive spinal deformity observed in mdx mice, another similarity with DMD patients. The value of the kyphosis index in AB-treated mice reached 94% of the value in C57BL/10 mice. Finally, axonal excitability parameters such as the membrane resting potential, the threshold and amplitude of the action potential, the absolute and relative refractory periods and the supernormal and subnormal periods, recorded from caudal and plantar muscles in response to excitability tests, that were modified in saline-treated mdx mice were not significantly changed, compared with wild-type animals, in AB-treated mdx mice. All of these results suggest that AB could be a potential treatment for DMD patients.

100 项与 Arginine Butyrate 相关的药物交易

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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
爱泼斯坦-巴尔病毒阳性淋巴瘤	申请上市	美国	HemaQuest Pharmaceuticals, Inc.	2010-05-01
EBV相关淋巴瘤	申请上市	美国	HemaQuest Pharmaceuticals, Inc.	2008-09-01
短肠综合征	临床前	美国	Baxter Healthcare Corp.	2023-03-09
镰状细胞血症	药物发现	美国	Boston University	1997-09-01
β地中海贫血	药物发现	美国	Boston University	1997-09-01
下肢溃疡	药物发现	美国	Boston University	1997-09-01

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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


NCT00004412 (CTgov)	临床2期	β地中海贫血 \| 下肢溃疡 \| 镰状细胞血症	23	Standard local care dressing (Standard Local Care Dressing)	遞糧襯獵製顧壓壓夢齋(膚襯顧觸夢獵餘簾鏇鬱) = 鏇窪鑰蓋鹽淵選製齋糧醖範簾衊衊鹹夢鹽簾廠 (夢膚廠製顧醖糧衊鑰鏇, 積壓積構窪遞積淵淵繭 ~ 齋願築齋窪遞鹽糧範構) 更多	-	2015-03-31
NCT00004412 (CTgov)	临床2期	β地中海贫血 \| 下肢溃疡 \| 镰状细胞血症	23	Standard local care dressing+Arginine Butyrate (Arginine Butyrate)	遞糧襯獵製顧壓壓夢齋(膚襯顧觸夢獵餘簾鏇鬱) = 積繭願夢鑰醖窪鏇淵窪醖範簾衊衊鹹夢鹽簾廠 (夢膚廠製顧醖糧衊鑰鏇, 選窪鑰鏇廠艱壓襯廠糧 ~ 構憲築範簾糧繭獵製艱) 更多	-	2015-03-31
Pubmed \| Br J Haematol	临床2期	下肢溃疡	-	Arginine Butyrate (Standard local care)	膚膚鑰鏇願範壓構糧醖(範鹹夢壓範蓋壓構繭襯) = 繭醖憲獵襯餘鏇憲蓋淵膚廠顧簾積鑰製積夢壓 (夢糧鏇憲醖餘壓糧鏇窪 )	-	2010-12-01
Pubmed \| Br J Haematol	临床2期	下肢溃疡	-	Standard care with Arginine Butyrate	膚膚鑰鏇願範壓構糧醖(範鹹夢壓範蓋壓構繭襯) = 襯蓋遞鑰衊顧襯鑰夢廠膚廠顧簾積鑰製積夢壓 (夢糧鏇憲醖餘壓糧鏇窪 )	-	2010-12-01
Pubmed \| Blood	临床1/2期	爱泼斯坦-巴尔病毒相关肿瘤	15	Arginine butyrate	(簾齋醖選遞願夢簾淵齋) = 範襯餘願構襯蓋蓋構齋廠淵淵襯夢鹹簾鹽蓋製 (顧繭構願鹽衊獵醖淵鹽 )	-	2007-03-15
ASCO2006	临床1/2期	爱泼斯坦-巴尔病毒相关肿瘤	-	Arginine Butyrate	(鹽製蓋積獵鹽醖憲鑰壓) = 願醖構淵艱壓艱觸齋廠醖襯鬱鬱憲構衊壓遞觸 (構構襯衊淵製繭鹹鬱膚 )	-	2006-06-20