non-enzymatic

5-A-RU (5-Amino-6-(D-ribitylamino)uracil), a precursor of bacterial Riboflavin, is a mucosal-associated invariant T (MAIT) cells activator. 5-A-RU forms potent MAIT-activating antigens via non-enzymatic reactions with small molecules that are derived from other metabolic pathways.This compound is unstable in powder form and other related salt forms are recommended.

Etravirine (R165335) is a diarylpyrimidine non-nucleoside reverse transcriptase inhibitor. Etravirine is designed to be active against HIV isolates with mutations that confer resistance to the two most commonly prescribed first-generation NNRTIs. It can bind the enzyme reverse transcriptase (RT) in multiple conformations, both for native and mutant RT, thereby blocking the enzymatic activity of RT.

Pulcherriminic acid, a cyclic dipeptide antimicrobial compound predominantly found in Bacillus and yeast, exhibits a strong affinity for Fe3+. It chelates iron ions via a non-enzymatic reaction, forming the extracellular red pigment pulcherrimin. This pigment competes for iron nutrition, thereby exerting an antibacterial effect. Pulcherriminic acid holds significant potential for applications in the food, agriculture, and medical industries [1] [2].

(±)9-HEPE is produced by non-enzymatic oxidation of EPA. It contains equal amounts of 9(S)-HEPE and 9(R)-HEPE. The biological activity of (±)9-HEPE has not been clearly documented.

Advanced glycation end products (AGEs) are compounds formed by non-enzymatic chemical reactions following the bonding of sugars to proteins or lipids during diabetes, uremia, aging, rheumatic arthritis, and other conditions. A receptor for the AGEs (RAGE) binds certain members of this class to initiate cell signaling.[1][2] Pentosidine is a well-characterized natural AGE that is often used as a biomarker for the production of all AGEs. While pentosidine can be measured in urine, the majority of this AGE is catabolized before excretion.[3] Reference：[1]. Neeper, M., Schmidt, A.M., Brett, J., et al. Cloning and expression of a cell surface receptor for advanced glycosylation end products of proteins. The Journal of Biological Chemisty 267(21), 14998-15004 (1992).[2]. Brett, J., Schmidt, A.M., Yan, S.D., et al. Survey of the distribution of a newly characterized receptor for advanced glycation end products in tissues. American Journal of Pathology 143(6), 1699-1712 (1993).[3]. Miyata, T., Ueda, Y., Horie, K., et al. Renal catabolism of advanced glycation end products: The fate of pentosidine. Kidney International 53, 416-422 (1998).

(±)15-HEDE is produced by non-enzymatic oxidation of 11,14-eicosadienoic acid. There are no reports in the literature of biological activity associated with (±)15-HEDE.

(±)13-HODE is one of the two racemic monohydroxy fatty acids resulting from the non-enzymatic oxidation of linoleic acid. It is the principle hydroxylated fatty acid in human psoriatic skin scales, with a mean concentration of 17 ng/mg.[1]

(±)9-HODE is one of the two racemic monohydroxy fatty acids resulting from the non-enzymatic oxidation of linoleic acid. Approximately equal proportions of both isomers are found in mitochondrial and plasma membranes of rabbit reticulocytes. [1][2] Oxidized LDL contains significant amounts of esterified 9- and 13-HpODEs and HODEs. [3][4]

(±)5-HETE is one of the six monohydroxy fatty acids produced by the non-enzymatic oxidation of arachidonic acid. It contains equal amounts of 5(S)-HETE and 5(R)-HETE. (±)5-HETE induces the aggregation of isolated neutrophils with an IC50 value of 200 nM.[1]

(±)12-HEPE is produced by non-enzymatic oxidation of EPA. It contains equal amounts of 12(S)-HEPE and 12(R)-HEPE. The biological activity of (±)12-HEPE is likely mediated by one of the individual isomers, most commonly the 12(S) isomer in mammalian systems. 12-HEPE inhibits platelet aggregation with the same potency as 12-HETE, exhibiting IC50 values of 24 and 25 µM, respectively. [1] These compounds are also equipotent as inhibitors of U46619-induced contraction of rat aorta (IC50s = 8.6-8.8 µM).[2]

Leukotriene B4 (LTB4) compounds are produced by both enzymatic and non-enzymatic processes. The products of enzymatic origin, via Leukotriene A4 (LTA4) hydrolase, are stereospecifically 12(R). Non-enzymatic hydrolysis products are 50:50 mixtures at C-12, but are almost exclusively trans at C-6. Thus, the non-enzymatic hydrolysis product of LTA4 is 6-trans-12-epi LTB4. 12-epi LTB4 is an isomer which would not be expected to occur in either non-enzymatic hydrolysis products, or in the enzymatic products of LTA4 hydrolase. Compared to LTB4, 12-epi LTB4 has significantly reduced activity for the LTB4 receptor on human neutrophils (IC50 of 7.5 mM), and on guinea pig lung membranes with a (Ki of 4.7 mM). 12-epi LTB4 is an weak agonist at both the recombinant human BLT1 and BLT2 receptors, requiring approximately 10 mM for full activation of the receptor.

(±)18-HEPE is produced by non-enzymatic oxidation of EPA. It contains equal amounts of 18(S)-HEPE and 18(R)-HEPE. Specific biological activity attributed to (±)18-HEPE has not been documented.

(±)5-HEPE is produced by non-enzymatic oxidation of EPA. It contains equal amounts of 5(S)-HEPE and 5(R)-HEPE. The biological activity of (±)5-HEPE is likely mediated by one of the individual isomers, most commonly the 5(S) isomer in mammalian systems. EPA can be metabolized to 5-HEPE in human and bovine neutrophils, and human eosinophils, which is further metabolized to 5-oxoEPE and LTB5. The 5-series metabolites of EPA, namely 5-HEPE, 5-oxoEPE, and LTB5, have significantly decreased biological effects compared to the arachidonic acid-derived metabolites.

(±)11-HETE is one of the six monohydroxy fatty acids produced by the non-enzymatic oxidation of arachidonic acid . The individual R and S isomers of racemic HETEs have been separated and identified using chiral phase HPLC. The racemic HETEs have been quantified as an index of lipid peroxidation using GC/MS.

Pravastatin lactone is a metabolite of pravastatin , a hydroxymethylglutaryl-coenzyme A (HMG-CoA) reductase inhibitor that is a ring-hydroxylated metabolite of mevastatin . Pravastatin lactone is formed when pravastatin undergoes acid-catalyzed non-enzymatic lactonization in the stomach following oral administration.

(±)12-HETE is one of the six monohydroxy fatty acids produced by the non-enzymatic oxidation of arachidonic acid. The biological activity of (±)12-HETE is similar to that of its constituent enantiomers . It aggregates neutrophils with an EC50 value of 40 nM.[1] Reference：[1]. O'Flaherty, J.T., Thomas, M.J., Lees, C.J., et al. Neutrophil-aggregating activity of monohydroxyeicosatetraenoic acids. American Journal of Pathology 104, 55-62 (1981).

(±)9-HETE is one of the six monohydroxy fatty acids produced by the non-enzymatic oxidation of arachidonic acid. The individual R and S isomers of racemic HETEs have been separated and identified using chiral phase HPLC. The racemic HETEs have been quantified as an index of lipid peroxidation using GC/MS.

3-Methylglutaconic acid, a primary metabolite accumulating in 3-Methylglutaconic aciduria (MGTA), induces lipid and protein oxidation, while diminishing non-enzymatic antioxidant defenses in cerebral cortex supernatants, thereby promoting oxidative stress in the cerebral cortex. This compound is utilized in research concerning brain damage diseases [1].

Advanced glycation end products (AGEs) are compounds that are produced through non-enzymatic chemical reactions when sugars bond with proteins or lipids, occurring in conditions such as diabetes, uremia, aging, and rheumatic arthritis. A specific receptor, known as RAGE, interacts with select AGEs to trigger cell signaling. Pentosidine, a prominently studied natural AGE, serves as a common biomarker for assessing AGE production. Although pentosidine levels can be determined through urine analysis, it is predominantly broken down prior to excretion.

RECQL5-IN-1 is an orally active inhibitor of RECQL5 (targeting both enzymatic and non-enzymatic domains) and is a potent inhibitor of RECQL5 decapping activity (IC50 46.3 nM): RECQL5-IN-1 can be used to study breast cancer.

(±)15-HEPE is produced by non-enzymatic oxidation of EPA. It contains equal amounts of 15(S)-HEPE and 15(R)-HEPE. Specific biological activity attributed to (±)15-HEPE has not been documented.

Isoprostanes are produced by the non-enzymatic, free radical peroxidation of phospholipid-esterified arachidonic acid. They have been used as biomarkers of oxidative stress, but they also have been found to have potent biological activity. ent-8-iso-15(S)-Prostaglandin F2α (ent-8-iso-15(S)-PGF2α) is a potent vasoconstrictor of porcine retinal and brain microvessels with EC50 values of 15 and 24 nM, respectively. This isoprostane is about ten-fold more potent than 8-iso-PGF2α in a whole blood platelet aggregation inhibition assay.

(±)5-HETE, a monohydroxy fatty acid, emerges from the non-enzymatic oxidation of arachidonic acid and is one of six such derivatives. Its methyl ester variant exhibits no unique biological activity and serves as a provided standard. This methyl ester can also be present in oxidatively degraded polyunsaturated fatty acid (PUFA) methyl esters.

7-Biopterin is a 7-substituted pterin.1It is formed by non-enzymatic rearrangement of 4a-hydroxy-tetrahydropterin in the absence of pterin-4a-carbinolamine dehydratase (PCD)in vitroand levels are elevated in the urine of hyperphenylalaninemia patients carrying heterozygous mutations in the PCBD gene encoding PCD.1,2

8-iso Prostaglandin F2β (8-iso PGF2β) is an isomer of PGF2α of non-enzymatic origin. It is one of 64 possible isomers of PGF2α which can be produced by free radical peroxidation of arachidonic acid. 8-iso PGF2β exhibits very weak contraction of human umbilical vein artery and does not promote aggregation of human whole blood. However, 8-iso PGF2β moderately contracts both the canine and porcine pulmonary vein, although the effect is much weaker than that exhibited by other isoprostanes such as 8-iso PGE1, 8-iso PGE2, or 8-iso PGF2α. 8-iso-15-keto PGF2β is a potential metabolite of 8-iso PGF2β via the 15-hydroxy PG dehydrogenase pathway. There are no published reports on the formation or biological activity of 8-iso-15-keto PGF2β.

LV-320 is a potent and uncompetitive ATG4B inhibitor with an IC 50 of 24.5 μM and a K d of 16 μM. LV-320 inhibits ATG4B enzymatic activity, blocks autophagic flux in cells, and is stable, non-toxic and active in vivo. These findings suggest that LV-320 will serve as a relevant chemical tool to study the various roles of ATG4B in cancer and other contexts [1].

(±)8-HEPE is produced by non-enzymatic oxidation of EPA. It contains equal amounts of 8(S)-HEPE and 8(R)-HEPE. The ability of (±)8-HEPE to induce hatching of E. modestus and B. balanoides eggs is probably due to the presence of the 8(R) isomer within the racemic mixture.[1][2] Reference：[1]. Shing, T.K.M., Gibson, K.H., Wiley, J.R., et al. First total synthesis of a barnacle hatching factor 8(R)-hydroxy-eicosa-5(Z),9(E),11(Z)-pentaenoic acid. Tetrahedron Letters 35, 1067-1070 (1994).[2]. Hill, E.M., and Holland, D.L. Identification and egg hatching activity of monohydroxy fatty acid eicosanoids in the barnacle Balanus balanoides. Proceedings of the Royal Society of London Series B.Biological Sciences 247, 41-46 (1991).

2,3-Dinor-8-iso Prostaglandin F1α (2,3-dinor-8-iso PGF1α), an isoprostane and active metabolite of arachidonic acid deriving its formation from non-enzymatic free radical peroxidation, acts as an active metabolite of the platelet aggregation inhibitor 8-iso PGF2α. This compound exhibits vasoconstrictive properties in isolated porcine retinal and brain microvessels with EC50 values of 12.8 and 18.5 nM, respectively, yet it does not cause contraction in isolated rat aortic rings at a concentration of 31 µM. Further, at a concentration of 1 µM, it raises thromboxane B2 (TXB2) levels in isolated porcine brain slices, an effect reversible by thromboxane A synthase inhibitor CGS 12970, voltage-gated calcium channel inhibitor SKF 96365, or the nicotinic acetylcholine receptor (nAChR) antagonist α-conotoxin.

8,12-iso-iPF2α-VI, an isoprostane, arises from non-enzymatic, free radical-induced peroxidation of membrane lipids. It is the predominant isoprostane formed during lipid peroxidation and serves as a biomarker for oxidative stress. Detectable in hepatic tissue post CCl4-induced oxidative damage, 8,12-iso-iPF2α-VI levels are also elevated in the urine, blood, and cerebrospinal fluid of Alzheimer’s disease patients.

Secoisolariciresinol diglucoside (LGM2605) was cytoprotective in an in vitro model of iron overload-induced redox-inflammatory damage. Secoisolariciresinol diglucoside (25 mg/kg b.w.) exerts the antihyperglycemic effect by preventing the liver from peroxidation damage through inhibition of ROS level mediated increased level of enzymatic and non-enzymatic antioxidants.

7α-Hydroxycholesterol is a cholesterol oxide formed by both enzymatic and non-enzymatic oxidation. It can be used as a biomarker for lipid peroxidation.

Cgs 26303 is a potent non-peptidic inhibitor of neutral endopeptidase capable of protecting atrial natriuretic peptide from enzymatic degradation.

Prostaglandin B2 (PGB2) is a non-enzymatic dehydration product resulting from the treatment of PGE2 or PGA2 with strong base. It has weak agonist activity on TP receptors and can increase pulmonary blood pressure in the rabbit at relatively high doses (5 ug/kg). [1]

HIV-1 inhibitor-41 (Compound B23) is an orally active inhibitor of non-nucleoside HIV-1 reverse transcriptase with EC 50 values of 50 nM and 20.8 nM against mutant E138K strain and HIV-1 WT, respectively. HIV-1 inhibitor-41 exhibits low hERG inhibition, no apparent CYP enzymatic inhibition as well as no acute toxicity [1].

5(S),6(S)-DiHETE is one of the four diastereomeric 5,6-dihydroxy acids produced from the non-enzymatic hydrolysis of LTA4. 5(S),6(S)-DiHETE does not have significant leukotriene-like activity.