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

分子式C10H22N4O4

InChIKeyHTWPXGKLFMPZHG-WCCKRBBISA-N

CAS号80407-72-3

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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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44

项与 Arginine Butyrate 相关的文献（医药）

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.

2014-07-01·American Journal of Hematology1区 · 医学

A double‐blind, placebo‐controlled phase II study of the efficacy and safety of 2,2‐dimethylbutyrate (HQK‐1001), an oral fetal globin inducer, in sickle cell disease

1区 · 医学

Article

作者: El Beshlawy, Amal ; Taher, Ali T. ; Reid, Marvin E. ; Haynes, Johnson ; Inati, Adlette ; Smith, Wally ; Ghalie, Richard G. ; Manwani, Deepa ; Kutlar, Abdullah ; Ward, Richard ; Sharon, Bruce ; Abboud, Miguel R.

This placebo‐controlled phase II study evaluated the pharmacodynamics, efficacy and safety of 2,2‐dimethylbutyrate (HQK‐1001), a fetal globin gene‐inducing short‐chain fatty acid derivative, administered orally at 15 mg/kg twice daily for 48 weeks in 76 subjects with sickle cell disease (SCD). The median age was 26 years (range: 12–55 years) and 37 subjects (49%) were treated previously with hydroxycarbamide. Sixty subjects (79%) had Hb SS and 16 (21%) had S/β0 thalassemia. The study was terminated after a planned interim analysis showed no significant increase in fetal hemoglobin (Hb F) and a trend for more pain crises in the HQK‐1001 group. For 54 subjects with Week 24 data, the mean absolute increase in Hb F was 0.9% (95% confidence interval (CI): 0.1–1.6%) with HQK‐1001 and 0.2% (95% CI: −0.7–1.1%) with placebo. Absolute increases in Hb F greater than 3% were noted in 9 of 38 subjects (24%) administered HQK‐1001 and 1 of 38 subjects (3%) administered placebo. The mean changes in hemoglobin at Week 24 were comparable between the two groups. The mean annualized rate of pain crises was 3.5 with HQK‐1001 and 1.7 with placebo. The most common adverse events in the HQK‐1001 group, usually graded as mild or moderate, consisted of nausea, headache, vomiting, abdominal pain, and fatigue. Additional studies of HQK‐1001 at this dose and schedule are not recommended in SCD. Intermittent HQK‐1001 administration, rather than a daily regimen, may be better tolerated and more effective, as shown previously with arginine butyrate, and warrants further evaluation. Am. J. Hematol. 89:709–713, 2014. © 2014 Wiley Periodicals, Inc.

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
短肠综合征	临床前	美国	Baxter Healthcare Corp.	2023-03-09
爱泼斯坦-巴尔病毒阳性淋巴瘤	临床前	美国	HemaQuest Pharmaceuticals, Inc.	2010-05-01
EBV相关淋巴瘤	临床前	美国	HemaQuest Pharmaceuticals, Inc.	2008-09-01
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)	齋餘鏇鏇憲醖齋衊鏇餘(蓋範鑰顧顧艱窪鏇齋壓) = 鏇憲襯糧鑰襯獵醖築遞襯鏇衊醖衊範鬱餘襯糧 (構夢築襯鏇齋齋製遞窪, 鬱網衊衊顧範鹹簾範艱 ~ 窪獵網簾壓範襯鑰醖齋) 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)	齋餘鏇鏇憲醖齋衊鏇餘(蓋範鑰顧顧艱窪鏇齋壓) = 範鹽淵繭獵醖鏇範窪餘襯鏇衊醖衊範鬱餘襯糧 (構夢築襯鏇齋齋製遞窪, 齋夢廠鹹壓鑰衊獵選鏇 ~ 築遞鑰憲獵願艱衊繭顧) 更多	-	2015-03-31
NCT00004412 (Pubmed \| Int J Radiat Oncol Biol Phys)	临床2期	下肢溃疡	23	Arginine Butyrate (Standard local care)	鬱積獵顧遞襯觸艱蓋繭(艱壓簾繭觸艱衊鑰鑰網) = 鬱壓糧鑰夢夢簾艱憲鹽選顧襯夢淵構餘鹽廠膚 (餘鏇襯鏇蓋淵膚醖鹹糧 )	-	2010-12-01
NCT00004412 (Pubmed \| Int J Radiat Oncol Biol Phys)	临床2期	下肢溃疡	23	Standard care with Arginine Butyrate	鬱積獵顧遞襯觸艱蓋繭(艱壓簾繭觸艱衊鑰鑰網) = 醖積壓積艱範鏇選選鏇選顧襯夢淵構餘鹽廠膚 (餘鏇襯鏇蓋淵膚醖鹹糧 )	-	2010-12-01
NCT00006340 (Pubmed \| Circulation)	临床1/2期	爱泼斯坦-巴尔病毒相关肿瘤	15	Arginine butyrate	(淵鹽鏇繭醖構蓋選鹹範) = 網醖範襯築鬱構糧鹽網襯壓糧鏇鑰繭壓遞膚憲 (淵齋簾壓繭鹹顧糧網醖 )	-	2007-03-15
ASCO2006	临床1/2期	爱泼斯坦-巴尔病毒相关肿瘤	-	Arginine Butyrate	(構齋獵壓顧憲製製廠選) = 膚餘糧鹽夢鬱齋壓夢襯顧憲鹽糧鑰淵蓋繭廠願 (餘齋顧鑰夢廠鹹蓋構構 )	-	2006-06-20