endopeptidase

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

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

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

Sacubitril (AHU-377) is a potent NEP inhibitor with an IC50 of 5 nM and is a component of the heart failure medicine LCZ696.

Sacubitril Valsartan (LCZ696) is an orally bioavailable, dual angiotensin II receptor and neprilysin inhibitor for the treatment of hypertension and heart failure.

Racecadotril (Acetorphan) has been investigated for the basic science and treatment of Diarrhea, Acute Diarrhea, and Acute Gastroenteritis.

Sacubitril hemicalcium salt (AHU377 calcium salt) is a potent NEP inhibitor with an IC50 of 5 nM. Sacubitril hemicalcium salt is a component of the heart failure medicine LCZ696. Sacubitril hemicalcium salt is a prodrug of LBQ657, which is an inhibitor of the zinc metallopeptidase neprilysin. Neprilysin degrades a variety of vasoactive peptides such as atrial and brain natriuretic peptide, bradykinin, adrenomedullin, and endothelin-1. Inhibition of neprilysin leads to an increased level of these peptides and, thus, antihypertensive effects. Formulations containing AHU377 in combination with the angiotensin II receptor antagonist valsartan are used to treat hypertension and heart failure.

Salidroside (Rhodioloside) is a bioactive phenolic glycoside compound isolated from Rhodiola crenulata. It is a prolyl endopeptidase Inhibitor.

Desonide (Prednacinolone) is a synthetic glucocorticosteroid for topical use, with anti-inflammatory activity. Desonide binds to glucocorticoid receptors in the cytoplasm, and the ligand-receptor complex is translocated as a homodimer into the nucleus, where transcription activation via glucocorticoid response elements within glucocorticoid-responsive genes occur. This agent induces transcription of genes coding for anti-inflammatory proteins, including lipocortin-1, interleukin-10, interleukin-1 receptor antagonist and neutral endopeptidase. Increased synthesis of lipocortin-1 has an inhibitory effect on phospholipase A2, which in turn inhibits the release of arachidonic acid, thereby controlling the biosynthesis of potent mediators of inflammation such as prostaglandins and leukotrienes.

Sar-[D-Phe8]-des-Arg9-Bradykinin acetate is a potent and selective bradykinin B1 receptor agonist (EC50 = 9.02 nM in rabbit aorta) that is resistant to aminopeptidase, kininase I and II (ACE) and neutral endopeptidase cleavage. Exhibits hypotensive and angiogenic activity in vivo.

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

(Rac)-Daglutril (SLV 306 acetic acid) is the racemate form of Daglutril. Daglutril is an orally active, mixed neutral endopeptidase/endothelin converting enzyme inhibitor under development for the treatment of essential hypertension and congestive heart failure.

NEP-IN-1 is an inhibitor of neutral endopeptidase (NEP, IC50 = 2 nM) and can be used in studies about female sexual arousal disorders.

RR-11a analog (aza-peptide Michael acceptor, 7a) is an inhibitor of asparaginyl endopeptidase with IC50s of 4.5 nM, 4.5 nM and 31 nM for AE1 in Trichomonas Vaginalis, AE in Ixodes ricinus and AE in Schistosoma mansoni, respectively.

LHW090-A7 is an neutral endopeptidase (NEP) inhibitor, and an enzyme responsible for the metabolic inactivation of enkephalins.

Thiorphan is an neprilysin inhibitor (NEP; IC50 : 0.007 μM).

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.

Linderene acetate is a competitive inhibitor against Prolyl endopeptidase.

Sacubitrilat (LBQ-657) (LBQ657) is an effective inhibitor of active neprilysin (NEP).

KGP94 is an inhibitor of cysteine protease Cathepsin L(CTSL).

BR102910 (4-Thiazolecarboxamide, N-[2-[(2S)-2-cyano-4,4-difluoro-1-pyrrolidinyl]-2-oxoethyl]-2-[(3,4-dichlorophenyl)methyl]-) is a selective inhibitor of fibroblast activated protein (FAP).

RB 101 suppresses enkephalinase and aminopeptidases; biologically cleaved at disulfide to produce inhibitors of both aminopeptidase N and neutral endopeptidase.

MDK7677 is a selective inhibitor of cathepsin B endopeptidase and exopeptidase activities.

MDL-100173 is a dual angiotensin-converting enzyme (ACE)/neutral endopeptidase (NEP) inhibitor.

Pepsin is an endopeptidase that breaks down proteins into smaller peptides and amino acids that can be easily absorbed in the small intestine[1]. Pepsin is stable at pH ranges as high as pH 6. Above this pH, pepsin is rapidly irreversibly inactivated and elevation of pH of the reaction mixture to pH 8 results in complete inactivation of pepsin[2]. Pepsin has been posited to be a reliable biological marker of EER. An immunologic pepsin assay of combined sputum and saliva was determined to be 100% sensitive and 89% specific for detection of EER (based on pH-metry), and an enzymatic test of nasal lavage fluid (100% sensitivity and 92.5% specificity) demonstrated an increased incidence of EER in patients with chronic rhinosinusitis[3]. Cultured hypopharyngeal epithelial (FaDu) cells were exposed to human pepsin (0.1 mg/mL) at pH 7.4 for either 1 hour or 12 hours at 37°C and both mitochondria and Golgi complexes were clearly damaged. This finding reveals a novel mechanism by which pepsin could cause cell damage, potentially even in nonacidic refluxate[4].

Azidothiorphan is a photoaffinity ligand for the active site of the neutral endopeptidase 24.11. After ultraviolet irradiation the inhibitor binds irreversibly to the enzyme, and photolabeling occurs at the active site. The competitive inhibitor thiorphan protects the endopeptidase from inactivation.

Aladotrilat is an inhibitor of neutral endopeptidase. Its prodrug is aladrotril.

Aminopeptidase N (AP-N) inhibitor is a reversible inhibitor of AP-N/CD13 (IC50 = 25 μM). It is selective for AP-N/CD13 over matrix metalloproteinase-9 (MMP-9), angiotensin converting enzyme (ACE), neutral endopeptidase (NEP), γ-glutamyl transpeptidase, and the serine proteases dipeptidyl peptidase 4 (DPP-4) and cathepsin G at a concentration of 1 mM. AP-N inhibitor is non-cytotoxic to U937 cells at a concentration of 100 μM.

Picornain 3C, a protease present in picornaviruses, exhibits endopeptidase activity by specifically cleaving Gln-Gly bonds within the poliovirus polyprotein and, through substitution, cleaves Glu for Gln, and Ser or Thr for Gly in other picornaviruses. This protease operates on non-terminal sequences and intermediates between serine peptidase chymotrypsin and cysteine peptidase papain, showcasing its role in viral polyprotein processing [1].

Potent and selective bradykinin B1 receptor agonist (EC50 = 9.02 nM in rabbit aorta) that is resistant to aminopeptidase, kininase I and II (ACE) and neutral endopeptidase cleavage. Exhibits hypotensive and angiogenic activity in vivo.

Bradykinin (1-7), an amino-truncated peptide derived from Bradykinin, is a metabolite formed through enzymatic cleavage by endopeptidase.

Candoxatrilat (U 73967, UK69578) is an active neutral endopeptidase inhibitor that reduces atrial natriuretic peptide degradation.

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].

Z-321 is an inhibitor of prolyl endopeptidase.

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).

NSC-84096 is an endopeptidase activity inhibitor of botulinum neurotoxin type A light chain (rBoNT/A-LC).

Ecadotril is a neutral endopeptidase (NEP) inhibitor, which plays an anti hypertensive role.

P516-0475 is a novel chemical inducer of Streptococcus quorum sensing acts by inhibiting the pheromone-degrading endopeptidase PepO. This compound induces quorum sensing by stabilizing SHP pheromones in culture.

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.

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.

NEP-IN-2 is a neutral endopeptidase inhibitor used in the research of proliferation in atherosclerosis and restenosis.

Hemopressin(rat) is a bioactive endogenous peptide substrate for endopeptidase 24.15, neurolysin and ACE. Ki values are 27.76, 3.43 and 1.87 μM respectively.

GLP-1(28-36)amide TFA, a C-terminal nonapeptide derived from GLP-1 cleavage by neutral endopeptidase (NEP), is an antioxidant that targets mitochondria and inhibits mitochondrial permeability transition (MPT), demonstrating anti-diabetic and cardioprotective effects [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].

APE-IN-1 can be used for the early diagnosis and drug research of Alzheimer's disease. APE-IN-1 is a potent Asparagine endopeptidase (AEP) inhibitor with IC 50 value of 89 nM [1].

Met-Arg-Phe-Ala, a peptide, serves as a potent competitive inhibitor of enkephalin-generating endopeptidase (EGE) and is utilized in neurological disease research [1].

Sampatrilat is an effecive and orally active vasopeptidase inhibitor of ACE and neutral endopeptidase. Sampatrilat inhibits C-domain ACE (Ki=13.8 nM) 12.4-fold more potent than that for the N-domain (Ki=171.9 nM).

PL-3994, a natriuretic peptide receptor-A (NPR-A) agonist resistant to neutral endopeptidase, functions as a bronchodilator, eliciting a concentration-dependent relaxation of pre-contracted guinea-pig trachea, evidenced by an IC50 of 42.7 nM [1].

Phosphoramidon is a membrane metallo-endopeptidase & endothelin-converting enzyme inhibitor and thermolysin inhibitor, which is obtained from culture filtrate of Streptomyces tanashiensis.