prolyl endopeptidase

Prolyl Endopeptidase is highly active in the brain and other tissues, where it degrades peptides containing proline, such as Substance P, neuropeptide Y, gonadotropin-releasing hormone, thyrotropin-releasing hormone, bradykinin, and angiotensin II. This enzyme is utilized in researching neuropsychiatric disorders including stress disorders, depression, and schizophrenia.

Y-29794 Tosylate (Y-29794) is an orally active, effective, and specific non-peptide-prolyl endopeptidase (PPCE) inhibitor.

Z-Pro-Pro-CHO acts as a prolyl oligopeptidase inhibitor with half-maximal inhibitory concentrations (IC50) of 0.16 μM for human prolyl oligopeptidase and 0.01 μM for Schistosoma mansoni prolyl oligopeptidase [1].

Z-Pro-Pro-aldehyde-dimethyl acetal is a potent prolyl endopeptidase (PREP) inhibitor, effectively impeding the activity of this cytoplasmic serine endoprotease with an IC50 of 12 nM. Its significance lies in its role in modulating cognitive dysfunction associated with aging and neurodegenerative conditions, such as Alzheimer's disease [1] [2].

Prolyl Endopeptidase Inhibitor 1 is a potent inhibitor of prolyl endopeptidase (PEP; PE)(Ki : 15 nM) , has anti-amnesic effect.

Prolyl Endopeptidase Inhibitor 2 (Compound 8), a proline endopeptidase (PEP) inhibitor, exhibits an IC50 value of 31.11 μM. This compound is applicable in research related to neurodegenerative diseases [1].

Salidroside is a bioactive phenolic glycoside compound isolated from Rhodiola rosea and is a prolyl endopeptidase inhibitor. Salidroside can alleviate cachexia symptoms in a tumor cachexia mouse model by activating mTOR signaling and protect dopaminergic neurons by enhancing PINK1 Parkin-mediated mitochondrial autophagy. Salidroside can also inhibit the growth of cancer cells by regulating the CDK4-cyclin D1 pathway to block the G1 phase and or regulating the Cdc2-cyclin B1 pathway to block the G2 phase.

Baicalein (5,6,7-Trihydroxyflavone) is a xanthine oxidase inhibitor.

N-Ethylmaleimide (NEM) is a reagent for alkylation of free sulfhydryl groups, a cysteine protease inhibitor used in experimental biochemistry. N-Ethylmaleimide is also a deubiquitinating enzyme inhibitor that specifically inhibits phosphate transport in mitochondria.

Baicalin (Baicalein 7-O-β-D-glucuronide) is a prolyl endopeptidase inhibitor isolated from scutellaria baicalensis, with antioxidant, anti-tumor, anti-HIV properties.

KYP-2047 is a very potent, selective Prolyl oligopeptidase (POP) inhibitor.

Z-321 is an inhibitor of prolyl endopeptidase.

S 17092 (S 17092-1) is a potent inhibitor of cerebral prolyl-endopeptidase (PEP) with an IC50 value of 1.2 nM, used in research on memory impairment and cognitive disorders related to cerebral aging [1].

HUP-55 is a prolyl endopeptidase inhibitor with an IC50 of 5 nM, shown to mitigate α-synuclein dimerization in Neuro2a cells, stimulate autophagy in HEK293 cells, and lower hydrogen peroxide-evoked reactive oxygen species (ROS) production in SH-SY5Y cells at a 10 µM concentration. Additionally, administration of HUP-55 at a dosage of 10 mg kg reduces ipsilateral paw use and diminishes striatal oligomeric α-synuclein concentrations in a Parkinson's disease mouse model, which is induced through adenoviral vector-mediated overexpression of α-synuclein (AAV-αSyn).

JTP-4819 is a potent and selective prolyl endopeptidase (PEP) inhibitor with potential for treating Alzheimer's disease. At nanomolar concentrations, it inhibited the degradation of substance P, arginine-vasopressin, and thyrotropin-releasing hormone by PEP in supernatants of the rat cerebral cortex and hippocampus. Repeated administration of JTP-4819 reversed the aging-induced decrease in brain substance P-like and thyrotropin-releasing hormone-like immunoreactivity, suggesting it may improve the imbalance of peptidergic neuronal systems that develops with senescence by inhibiting PEP activity. Additionally, JTP-4819 increased acetylcholine release from the frontal cortex and hippocampus, regions closely associated with memory, in both young and aged rats.

Oroxylin A-7-O-glucuronide (Oroxylin A Glucoronide) and wogonoside should also be served as the chemical markers together with baicalin for the quality control of herbs and proprietary traditional Chinese medicine (PTCM) products of radix Scutellariae. Oroxylin A 7-O-glucuronide, Oroxin A, and Oroxin B can bind to the stem region of α-hemolysin (α-HL), when inhibiting the hemolytic activity of α-HL. Oroxylin A 7-O-glucuronide and 4', 5, 7-trihydroxy-6-methoxyflavone at a concentration of 100 microM inhibit 34 and 43% of total prolyl oligopeptidase (POP) activity, respectively.

β-Elemonic Acid (3-Oxotirucallenoic Acid) exhibits anti-inflammatory effects. Beta-Elemonic acid inhibits proliferation by inducing hypoploid cells and cell apoptosis, the anticancer effects of beta-Elemonic acid are related to the MAPK signaling pathway, ROS activation and glutathione depletion in human A549 lung cancer cells. Beta-Elemonic acid exhibits prolyl endopeptidase inhibitory activities.

Rosenonolactone exhibits inhibitory activity against prolyl endopeptidase and thrombin.

Z-Pro-prolinal (N-Benzyloxycarbonyl-L-prolyl-L-prolinal) is a specific and orally active inhibitor of prolyl endopeptidase (PREP) with an IC50 of 0.4 nM against porcine PREP [1] [2] [3].

Inhibitor of prolyl endopeptidase

DOTA.SA.FAPi TFA is a bifunctional chelator composed of squaric acid (squaric acid) and UAMC1110, integrating the properties of DATA5m and DOTA. It exhibits inhibitory activity against fibroblast activation protein (FAP) with an IC50 of 0.9 nM and targets the prolyl endopeptidase (PREP) with an IC50 of 5.4 μM. After labeling with 68Ga, DOTA.SA.FAPi TFA serves as a PET tracer for cancer research.

ONO-1603, a prolyl endopeptidase inhibitor, is used potentially for the treatment of Alzheimer's disease.

Picromycin is a 14-membered macrolide antibiotic and Prolyl endopeptidase (PREP) inhibitor. Pikromycin shows activity against gram-positive bacteria including mycobacteria.

Z-Thioprolyl-Thioproline is a prolyl endopeptidase inhibitor derived from bovine brain, exhibiting inhibition constants of IC50 = 16 µM and Ki = 37 µM. This compound is utilized in the investigation of neurological disorders, including memory and cognitive disorders [1].