advanced glycation end products

Advanced glycation end products are the outcome of non-enzymatic glycation reactions involving biomolecules such as proteins, lipids, nucleic acids, and reducing sugars. Advanced glycation end products are frequently employed in investigating pathological mechanisms associated with diabetes, ageing, and chronic diseases.

Ipriflavone (Osteofix) (Osteofix) is a feed additive and a catabolic agent. It is used to inhibit bone resorption.

Azeliragon (TTP488) is an antagonist at the Receptor for Advanced Glycation End products; is evaluated as a potential treatment for patients with mild-to-moderate Alzheimer_acute_s disease (AD).

FPS-ZM1 is a high-affinity, RAGE-specific inhibitor that obstructs Aβ binding to the V domain of RAGE.

4'-Methoxyresveratrol (4'-O-Methylresveratrol) is a natural product from the roots of *Rheum palmatum* L., with significant hypoglycemic, anti-inflammatory, and antioxidant effects. 4'-Methoxyresveratrol alleviates AGE-induced inflammation by suppressing RAGE-mediated MAPK/NF-κB signaling pathway and NLRP3 inflammasome activation.

D-Psicose (D-Allulose) is an orally active rare sugar. It effectively inhibits p38-MAPK phosphorylation and MCP-1 expression, while blocking the AGEs/RAGE/NF-kappaB signaling pathway. D-Psicose demonstrates significant bioactivity in research involving pancreatic beta-islet protection, hyperglycemia improvement, lipid metabolism regulation, and the mitigation of high-fat diet-induced non-alcoholic fatty liver disease (NAFLD).

ABR-238901 is an oral, active S100A8/A9 blocker that inhibits the interaction of S100A8/A9 with its receptors RAGE(receptor for advanced glycation end products) and TLR4 (toll-like receptor 4). ABR-238901 has potential as a compound for the treatment of myocardial infarction (MI).

Pyridoxylamine (pyridoxamine) is an inhibitor of advanced glycation end production (AGEs) and lipoxidation end products (ALEs).

Fructosyl-lysine is the precursor to glucosepane. Fructosyl-lysine is a lysine–arginine protein cross-link that can be an indicator in diabetes detection. Fructosyl-lysine is an amadori glycation product from the reaction of glucose and lysine by the Maillard reaction.

RuDiOBn exhibits low antioxidant activity by scavenging DPPH and ABTS free radicals with scavenging rates of 13.2% and 5.9% at a concentration of 100 μg/mL. It inhibits collagen glycation and reduces the formation of advanced glycation end-products (AGE) with an IC50 of 2.45 μg/mL. RuDiOBn also enhances fibroblast proliferation and migration, stimulates collagen synthesis, and aids in skin repair and regeneration while inhibiting collagenase.

(R)-DRF053 is a CDK inhibitor that suppresses Cdk5 and facilitates the formation of ductal progenitor β cells. Additionally, (R)-DRF053 inhibits the uptake of Dil-ox-LDL and the expression of the CD36 gene in U937 cells induced by advanced glycation end-products (AGEs).

MG-H1 is a ligand for the receptor for advanced glycation end-products (RAGE), with a Kd value of 4.12 nM. It is capable of binding to human umbilical vein endothelial cells. MG-H1 is applicable in diabetes research.

Homocarnosine is a brain-specific dipeptide composed of γ-aminobutyric acid (GABA) and histidine. As an inhibitory neurotransmitter, homocarnosine is synthesized from GABA within neurons and exerts anticonvulsant effects by enhancing GABA receptor signaling pathways. Homocarnosine also possesses antioxidant and anti-inflammatory properties; it scavenges peroxyl radicals, chelates transition metal ions such as copper, prevents oxidative damage to DNA, and inhibits the formation of advanced glycation end products (AGEs).

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).

RAGE/SERT-IN-1 is a potent, orally active inhibitor of advanced glycation end products (RAGE) and serotonin transporter (SERT), with IC50 values of 8.26 μM and 31.09 nM, respectively. It demonstrates significant neuroprotective effects against Aβ25-35-induced neuronal damage and alleviates depressive behavior in mice. RAGE/SERT-IN-1 is useful for research on the comorbidity of Alzheimer's disease and depression [1].

Gemigliptin Tartrate (LC15-0444 tartrate) is a highly selective, reversible and competitive inhibitor of dipeptidyl peptidase-4 (DPP-4). It has an IC50 of 10.3 nM for human recombinant DPP-4. Gemigliptin tartrate exhibits potent anti-glycation properties.

Homocarnosine TFA, a unique dipeptide of γ-aminobutyric acid (GABA) and histidine found in the brain, acts as an inhibitory neuromodulator synthesized from GABA within neurons. It exhibits anticonvulsant effects [1], and possesses antioxidant and anti-inflammatory properties, prevents DNA damage, and inhibits the formation of advanced glycation end-products [2].

Lucidin-ω-Me ether (Compound 2), extracted from the roots of Knoxia valerianoides, exhibits inhibitory activity against the formation of advanced glycation end products (AGEs) with an IC50 of 62.79 μM in vitro [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.

NecroX-7 (LC-280126) is a potent free radical scavenger and HMGB1 (high-mobility group box 1) inhibitor. It serves as an antidote to acetaminophen toxicity and exerts a protective effect by preventing HMGB1 release in ischemia/reperfusion injury. Additionally, NecroX-7 inhibits HMGB1-induced release of TNF and IL-6 and the expression of TLR-4 and receptor for advanced glycation end products. This compound may be used for graft-versus-host disease (GVHD) research [1].

Indole-4-carboxaldehyde-13C is the 13C-labeled version of Indole-4-carboxaldehyde, a precursor to ergot alkaloids. Indole-4-carboxaldehyde can mitigate the expression of inflammation-related genes such as TNF-α and IFN-γ induced by methylglyoxal (MGO) through NF-κB activation, showing no toxicity to HepG2 cells. It also reduces the formation of advanced glycation end-products (AGEs) induced by MGO and the expression of their receptor (RAGE). This compound is useful in studying hepatic steatosis.

Chebulic acid, a phenolcarboxylic acid compound isolated from Terminalia chebula, exhibits potent antioxidant activity by breaking protein cross-links induced by advanced glycation end-products (AGEs) and inhibiting AGE formation. It may also counteract AGE-induced endothelial cell dysfunction, suggesting it as a potential intervention for diabetic vascular complications.

Cassiaside C (Toralactone 9-O-β-D-gentiobioside), a naphthopyrone extracted from Cassia tora seeds, demonstrates in vitro inhibitory activity against the formation of advanced glycation end products (AGE).

Rubrofusarin gentiobioside (Rubrofusarin-6-O-beta-D-gentiobioside) can significantly decrease the expression of TGF-beta1 and fibronectin and NF-kappaB DNA binding activity, suggests that it has potential as a preventive agent for advanced glycation end products-related diabetic complications.