ARUNDIC ACID

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C11H22O2
Molecular Weight	186.2912
Optical Activity	( - )
Defined Stereocenters	1 / 1
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CCCCCC[C@@H](CCC)C(O)=O

InChI

InChIKey=YCYMCMYLORLIJX-SNVBAGLBSA-N

InChI=1S/C11H22O2/c1-3-5-6-7-9-10(8-4-2)11(12)13/h10H,3-9H2,1-2H3,(H,12,13)/t10-/m1/s1

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Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/14619409
Curator's Comment: description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/16303147 | https://clinicaltrials.gov/ct2/show/NCT00229177 | https://clinicaltrials.gov/ct2/show/NCT00403104 | https://clinicaltrials.gov/ct2/show/NCT00212693 | https://www.ncbi.nlm.nih.gov/pubmed/28280459 | https://www.ncbi.nlm.nih.gov/pubmed/1355269

ARUNDIC ACID (ONO-2506) is an enantiomeric, three carbon atom homolog of valproic acid under development by ONO Pharmaceutical for the potential treatment of stroke, as well as Amyotrophic Lateral Sclerosis and Parkinson's disease. The injectable formulation (Proglia) is finished phase III trials for acute-phase cerebral infarction, and the oral formulation (Cereact) is finished phase II trials in the UK for Alzheimer's disease (AD) and Parkinson's disease (PD). ARUNDIC ACID restores normal astrocyte functions after brain damage by preventing reactive astrocytosis, by activating astrocytic GABAA receptors and suppressing GABA transferase. ARUNDIC ACID inhibits S-100β synthesis in activated cultured astrocytes. This agent has additional antiglutamate and antiinflammatory COX-2 inhibitor properties

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
S100 beta biosynthetic process 1 Target ID: GO:0048152 Sources: https://www.ncbi.nlm.nih.gov/pubmed/12045671	Inhibitor 8297

Conditions

Condition	Modality	Highest Phase	Product
Stroke 144 Sources: https://clinicaltrials.gov/ct2/show/NCT00229177	Primary	Phase III 656	Unknown Approved Use Unknown
Amyotrophic lateral sclerosis 41 Sources: https://clinicaltrials.gov/ct2/show/NCT00403104	Primary	Phase II 1132	Unknown Approved Use Unknown
Parkinson's disease 226 Sources: https://clinicaltrials.gov/ct2/show/NCT00212693	Primary	Phase II 1132	Unknown Approved Use Unknown

PubMed

Title	Date	PubMed
Gateways to clinical trials.	2004 Apr	15148527
Arundic acid, an astrocyte-modulating agent, protects dopaminergic neurons against MPTP neurotoxicity in mice.	2004 Dec 24	15567338
Arundic acid (ONO-2506) ameliorates delayed ischemic brain damage by preventing astrocytic overproduction of S100B.	2005 Apr	15857298
Arundic Acid ameliorates cerebral amyloidosis and gliosis in Alzheimer transgenic mice.	2006 Aug	16709678
Neuroprotective effect of arundic acid, an astrocyte-modulating agent, in mouse brain against MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) neurotoxicity.	2006 Mar	16303147
Inflammatory mechanisms in ischemic stroke: therapeutic approaches.	2009 Nov 17	19919699
Immunohistochemical analysis of brain lesions using S100B and glial fibrillary acidic protein antibodies in arundic acid- (ONO-2506) treated stroke-prone spontaneously hypertensive rats.	2009 Oct	19657585
Targeting S100B in Cerebral Ischemia and in Alzheimer's Disease.	2010	20862385
S100B Protein, A Damage-Associated Molecular Pattern Protein in the Brain and Heart, and Beyond.	2010	20827421
Effects of S100B on Serotonergic Plasticity and Neuroinflammation in the Hippocampus in Down Syndrome and Alzheimer's Disease: Studies in an S100B Overexpressing Mouse Model.	2010	20827311
S100b counteracts neurodegeneration of rat cholinergic neurons in brain slices after oxygen-glucose deprivation.	2010	20508809
A systematic review of clinical trials of pharmacological interventions for acute ischaemic stroke (1955-2008) that were completed, but not published in full.	2010 Apr 22	20412562
PSAPP mice exhibit regionally selective reductions in gliosis and plaque deposition in response to S100B ablation.	2010 Nov 16	21080947

Patents

Sample Use Guides

In Vivo Use Guide

Stroke: Once daily one-hour intravenous infusion at 8 or 12/mg/kg/hr for 7 days Amyotrophic Lateral Sclerosis: PO 1200 mg QD / 18 months

Route of Administration: Other

In Vitro Use Guide

E13.5 embryos were dissected in filter sterilized Krebs (containing the following in mM: 120.9 NaCl, 5.9 KCl, 1.2 MgCl2, 1.2 NaH2PO4, 14.4 NaHCO3, 2.5 CaCl2, and 11.5 glucose). The entire embryonic gut, including the stomach, small intestine and colon, was removed and pinned in small Sylgard dishes using 50 mm diameter tungsten wire, as described previously (Shyer et al., 2013). Gut explants were cultured in 2 ml of DMEM/F12 with 1% penicillin/streptomycin. Arundic acid (ONO-2506, Tocris Bioscience, catalog #4530) was dissolved in DMSO and added to the culture media. S100B (Sigma, cat #A6677) was dissolved in Krebs or Dulbecco’s phosphate buffered saline (DPBS) and also added to the culture media, either alone, or in combination with arundic acid. Appropriate vehicle control cultures were also performed. All preparations were incubated for 48 h at 37_C, 5% CO2 with media refreshed at 24 h.

Name

Type

Language

ARUNDIC ACID

Official Name

English

ONO-2506

Code

English

MK-0724

Code

English

arundic acid [INN]

Common Name

English

Arundic acid [WHO-DD]

Common Name

English

ARUNDIC ACID [JAN]

Common Name

English

ONO-2506PO

Code

English

(2R)-2-PROPYLOCTANOIC ACID

Systematic Name

English

MK0724

Code

English

Classification Tree Code System Code

NCI_THESAURUS

C1509