876150-14-0

Basic information

• Product Name: Pentanedioic acid, 2-oxo-, 1-octyl ester
• CAS NO: 876150-14-0
• Molecular Formula: C13H22O5
• Molecular Weight: 258.315
• Mol File: 876150-14-0.mol
• Article Data: 3

Chemical Properties

• CAS DataBase Reference: Pentanedioic acid, 2-oxo-, 1-octyl ester(CAS DataBase Reference)
• NIST Chemistry Reference: Pentanedioic acid, 2-oxo-, 1-octyl ester(876150-14-0)
• EPA Substance Registry System: Pentanedioic acid, 2-oxo-, 1-octyl ester(876150-14-0)

Safety Data

• Hazardous Substances Data: 876150-14-0(Hazardous Substances Data)

Usage

Description

Pentanedioic acid, 2-oxo-, 1-octyl ester, also known as Octyl-α-ketoglutarate, is a chemical compound that serves as a substrate for prolyl hydroxylases. It is characterized by its ability to accumulate rapidly in cells with a dysfunctional tricarboxylic acid cycle. This unique property makes it a promising candidate for various applications in different industries.

Uses

Used in Pharmaceutical Industry:
Pentanedioic acid, 2-oxo-, 1-octyl ester is used as a pharmaceutical agent for its ability to prevent succinate or fumarate-mediated inhibition of prolyl hydroxylases. This makes it a potential candidate for the development of treatments targeting diseases associated with the tricarboxylic acid cycle dysfunction.
Used in Drug Development:
In the field of drug development, Pentanedioic acid, 2-oxo-, 1-octyl ester is used as a research tool to study the effects of tricarboxylic acid cycle dysfunction on cellular processes. Its rapid accumulation in affected cells allows researchers to investigate the underlying mechanisms and develop targeted therapies for related conditions.
Used in Biochemical Research:
Pentanedioic acid, 2-oxo-, 1-octyl ester is utilized as a biochemical research compound to understand the role of prolyl hydroxylases in various cellular processes. Its ability to prevent succinate or fumarate-mediated inhibition of these enzymes aids in elucidating their functions and potential applications in therapeutic interventions.

Biological Activity

octyl-α-ketoglutarate is a stable, cell-permeable form of α-ketoglutarate, a substrate of prolyl hydroxylases (phd) [1][2].the high turnover of hifα is initiated by prolyl hydroxylases (phd), which hydroxylate proline residues on the oxygen-dependent degradation (odd) domain of hifα, facilitating ubiquitination and degradation. to catalyze proline hydroxylation, phds convert molecular oxygen and α-ketoglutarate to carbon dioxide and succinate [2]. loss of idh1 activity would reduce cellular levels of α-kg [3].octyl-α-ketoglutarate is a cell-permeating α-ketoglutarate derivative, which built up rapidly and preferentially in cells with a dysfunctional tca cycle. octyl-α-ketoglutarate increased intracellular levels of freeα-ketoglutaric acid by approximately fourfold. in hek293-derived cell lines expressing both a gfp-odd fusion protein and ha-tagged pvhl, octyl-α-ketoglutarate reactivated phd activity inhibited by succinate or fumarate. octyl-α-ketoglutarate restored hydroxylation and targeted hif1 for ubiquitylation and proteasomally mediated degradation [2]. octyl-α-ketoglutarate inhibited the hif-1α induction caused by idh1 knockdown in hela cells or overexpression of idh1r132h mutant in u-87mg cells, suggesting a reduction in idh1 activity caused a reduction in α-kg levels that in turn led to stabilization of hif-1α [3].

references

[1]. gottlieb e, tomlinson ip. mitochondrial tumour suppressors: a genetic and biochemical update. nat rev cancer. 2005 nov;5(11):857-66.[2]. mackenzie ed, selak ma, tennant da, et al. cell-permeating alpha-ketoglutarate derivatives alleviate pseudohypoxia in succinate dehydrogenase-deficient cells. mol cell biol. 2007 may;27(9):3282-9. [3]. zhao s, lin y, xu w, et al. glioma-derived mutations in idh1 dominantly inhibit idh1 catalytic activity and induce hif-1alpha. science. 2009 apr 10;324(5924):261-5.

Upstream product

• 111-83-1 1-bromo-octane 
• 22202-68-2 α-ketoglutaric acid sodium salt 
• 35120-18-4 ethyl 1-bromocyclobutane-1-carboxylate 
• 14924-53-9 ethyl cyclobutylcarboxylate 
• 23519-90-6 1-cyclobutenecarboxylic acid 
• 1415100-67-2 octyl cyclobut-1-enecarboxylate 
• 1421780-82-6 C₁₃H₂₂O₄ 
• 111-87-5 octanol 

Relevant articles and documents

The metabolite α-ketoglutarate extends lifespan by inhibiting ATP synthase and TOR

Metabolism and ageing are intimately linked. Compared with ad libitum feeding, dietary restriction consistently extends lifespan and delays age-related diseases in evolutionarily diverse organisms. Similar conditions of nutrient limitation and genetic or pharmacological perturbations of nutrient or energy metabolism also have longevity benefits. Recently, several metabolites have been identified that modulate ageing; however, the molecular mechanisms underlying this are largely undefined. Here we show that α-ketoglutarate (α-KG), a tricarboxylic acid cycle intermediate, extends the lifespan of adult Caenorhabditis elegans. ATP synthase subunit β 2 is identified as a novel binding protein of α-KG using a small-molecule target identification strategy termed drug affinity responsive target stability (DARTS). The ATP synthase, also known as complex V of the mitochondrial electron transport chain, is the main cellular energy-generating machinery and is highly conserved throughout evolution. Although complete loss of mitochondrial function is detrimental, partial suppression of the electron transport chain has been shown to extend C. elegans lifespan. We show that α-KG inhibits ATP synthase and, similar to ATP synthase knockdown, inhibition by α-KG leads to reduced ATP content, decreased oxygen consumption, and increased autophagy in both C. elegans and mammalian cells. We provide evidence that the lifespan increase by α-KG requires ATP synthase subunit β and is dependent on target of rapamycin (TOR) downstream. Endogenous α-KG levels are increased on starvation and α-KG does not extend the lifespan of dietary-restricted animals, indicating that α-KG is a key metabolite that mediates longevity by dietary restriction. Our analyses uncover new molecular links between a common metabolite, a universal cellular energy generator and dietary restriction in the regulation of organismal lifespan, thus suggesting new strategies for the prevention and treatment of ageing and age-related diseases.

ALPHA-KETOGLUTARATES AND THEIR USE AS THERAPEUTIC AGENTS

The present invention relates generally to the field of pharmaceuticals and medicine. More particularly, the present invention relates to certain compounds (e.g., α-ketoglutarate compounds; compounds that activate HIFα hydroxylase; compounds that increases the level of α ketoglutarate, etc.) and their use in medicine, for example, in the treatment of cancer (e.g., cancer in which the activity of one of the enzymes in the tricarboxylic acid (TCA) cycle is down regulated), in the treatment of angiogenesis (e.g., hypoxia-induced angiogenesis). One preferred class of compounds are α-ketoglutarate compounds having a hydrophobic moiety that is, or is part of, an ester group formed from one of the acid groups of α ketogluartic acid; and pharmaceutically acceptable salts, solvates, amides, esters, ethers, N oxides, chemically protected forms, and prodrugs thereof.