Delving into the Latest Updates on Arginine Butyrate with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Target

thymidine kinase

Mechanism

thymidine kinase stimulants(Thymidine kinase stimulants)

Therapeutic Areas

Digestive System DisordersEndocrinology and Metabolic DiseaseOther Diseases

Active Indication

Short Bowel Syndrome

Inactive Indication

Anemia, Sickle CellBeta-ThalassemiaEpstein-Barr virus positive Lymphoma+ [2]

Originator Organization

Boston University

Active Organization

Baxter Healthcare Corp.

Inactive Organization

Boston UniversityHemaQuest Pharmaceuticals, Inc.

Drug Highest PhasePreclinical

First Approval Date-

RegulationOrphan Drug (US)

Login to view timeline

Structure

Molecular FormulaC10H22N4O4

InChIKeyHTWPXGKLFMPZHG-WCCKRBBISA-N

CAS Registry80407-72-3

View All Structures (2)

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.

Start Date01 Mar 1999

Sponsor / Collaborator

Boston University

100 Clinical Results associated with Arginine Butyrate

Login to view more data

100 Translational Medicine associated with Arginine Butyrate

Login to view more data

100 Patents (Medical) associated with Arginine Butyrate

Login to view more data

44

Literatures (Medical) associated with Arginine Butyrate

01 Sep 2022·Molecular Diagnosis & Therapy

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

Review

Author: 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.

01 Nov 2014·Neurobiology of DiseaseQ2 · MEDICINE

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

Q2 · MEDICINE

Article

Author: Roulot, Morgane ; Sebrié, Catherine ; Fromes, Yves ; Benoit, Evelyne ; Herbin, Marc ; 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.

01 Jul 2014·American Journal of HematologyQ1 · MEDICINE

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

Q1 · MEDICINE

Article

Author: 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 Deals associated with Arginine Butyrate

Login to view more data

R&D Status

10 top R&D records.

Login

to view more data

Indication	Highest Phase	Country/Location	Organization	Date
Short Bowel Syndrome	Preclinical	US	Baxter Healthcare Corp.	09 Mar 2023
Epstein-Barr virus positive Lymphoma	Preclinical	US	HemaQuest Pharmaceuticals, Inc.	01 May 2010
Epstein-Barr Virus-Related Lymphoma	Preclinical	US	HemaQuest Pharmaceuticals, Inc.	01 Sep 2008
Anemia, Sickle Cell	Discovery	US	Boston University	01 Sep 1997
Beta-Thalassemia	Discovery	US	Boston University	01 Sep 1997
Leg Ulcer	Discovery	US	Boston University	01 Sep 1997

Login to view more data

Clinical Result

Indication

Phase

Evaluation

View All Results

Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT00004412 (CTgov)	Phase 2	Beta-Thalassemia \| Leg Ulcer \| Anemia, Sickle Cell	23	Standard local care dressing (Standard Local Care Dressing)	ivaaorehfa(hixxcrcbuw) = uzojfsjzfe qmuuehcwql (ytjzmtdoaw, xphpxpwzho - wucwgomjpe) View more	-	31 Mar 2015
NCT00004412 (CTgov)	Phase 2	Beta-Thalassemia \| Leg Ulcer \| Anemia, Sickle Cell	23	Standard local care dressing+Arginine Butyrate (Arginine Butyrate)	ivaaorehfa(hixxcrcbuw) = ccylcjoqmt qmuuehcwql (ytjzmtdoaw, ywogbbqmzo - uwitjyrhox) View more	-	31 Mar 2015
NCT00004412 (Pubmed \| Int J Radiat Oncol Biol Phys)	Phase 2	Leg Ulcer	23	Arginine Butyrate (Standard local care)	wseouxvjbg(rfbbrlzypy) = qhgrjjseel kdadklxlyg (wjyeemblbi )	-	01 Dec 2010
NCT00004412 (Pubmed \| Int J Radiat Oncol Biol Phys)	Phase 2	Leg Ulcer	23	Standard care with Arginine Butyrate	wseouxvjbg(rfbbrlzypy) = bwtqigztdx kdadklxlyg (wjyeemblbi )	-	01 Dec 2010
NCT00006340 (Pubmed \| Circulation)	Phase 1/2	Epstein-Barr virus associated Neoplasms	15	Arginine butyrate	(onebshlwls) = sctfqkzexm mephanvkmc (trjsxerdpl )	-	15 Mar 2007
ASCO2006	Phase 1/2	Epstein-Barr virus associated Neoplasms	-	Arginine Butyrate	(lalzxivivi) = efhpxeezoj ameelomqto (ukvmlmszxu )	-	20 Jun 2006