Genomes and Genes
serine proteinase inhibitors
Summary: Exogenous or endogenous compounds which inhibit SERINE ENDOPEPTIDASES.
- Gatto M, Iaccarino L, Ghirardello A, Bassi N, Pontisso P, Punzi L, et al. Serpins, immunity and autoimmunity: old molecules, new functions. Clin Rev Allergy Immunol. 2013;45:267-80 pubmed publisher..Here, we provide an overview of serpin origin, function, and dysfunction, focusing on human serpins and ov-serpins, with a hub on SERPINB3. ..
- Almonte A, Sweatt J. Serine proteases, serine protease inhibitors, and protease-activated receptors: roles in synaptic function and behavior. Brain Res. 2011;1407:107-22 pubmed publisher..In this review, we discuss emerging roles for serine proteases in the regulation of mechanisms underlying synaptic plasticity and memory formation. ..
- Mulenga A, Khumthong R, Chalaire K. Ixodes scapularis tick serine proteinase inhibitor (serpin) gene family; annotation and transcriptional analysis. BMC Genomics. 2009;10:217 pubmed publisherb>Serine proteinase inhibitors (Serpins) are a large superfamily of structurally related, but functionally diverse proteins that control essential proteolytic pathways in most branches of life...
- Suzuki K. The multi-functional serpin, protein C inhibitor: beyond thrombosis and hemostasis. J Thromb Haemost. 2008;6:2017-26 pubmed publisher..Thus, PCI is a unique multi-functional serpin playing diverse roles in the thrombosis and hemostasis in multiple organs and tissues of a variety of species. ..
- Raboisson P, Lin T, Kock H, Vendeville S, Vreken W, McGowan D, et al. Discovery of novel potent and selective dipeptide hepatitis C virus NS3/4A serine protease inhibitors. Bioorg Med Chem Lett. 2008;18:5095-100 pubmed publisher..20 nM, EC(50)=3.7 nM), selective, and orally bioavailable dipeptide NS3/4A protease inhibitor, which has features attractive for further preclinical development. ..
- Millers E, Trabi M, Masci P, Lavin M, de Jersey J, Guddat L. Crystal structure of textilinin-1, a Kunitz-type serine protease inhibitor from the venom of the Australian common brown snake (Pseudonaja textilis). FEBS J. 2009;276:3163-75 pubmed publisher..5 nm versus 0.053 nm) and could also account for an observed narrower binding specificity. ..
- Fowell A, Nash K. Telaprevir: a new hope in the treatment of chronic hepatitis C?. Adv Ther. 2010;27:512-22 pubmed publisher..In this review, we summarize the pharmacology, pharmacokinetics, and results of phase 1 and 2 clinical trials of telaprevir, and discuss the likely role of this agent in the future management of CHC...
- Shimada T, Sugano N, Ikeda K, Shimada K, Iizuka T, Ito K. Protease-activated receptor 2 mediates interleukin-8 and intercellular adhesion molecule-1 expression in response to Aggregatibacter actinomycetemcomitans. Oral Microbiol Immunol. 2009;24:285-91 pubmed publisher..A. actinomycetemcomitans extract-induced IL-8 and ICAM-1 expression in gingival epithelial cells is mediated by PAR-2. ..
- Mueller N, Pattabiraman N, Ansarah Sobrinho C, Viswanathan P, Pierson T, Padmanabhan R. Identification and biochemical characterization of small-molecule inhibitors of west nile virus serine protease by a high-throughput screen. Antimicrob Agents Chemother. 2008;52:3385-93 pubmed publisher..Furthermore, compound B was capable of inhibiting West Nile virus RNA replication in cultured Vero cells (50% effective concentration, 1.4 +/- 0.4 microM; selectivity index, 100), presumably by inhibition of polyprotein processing. ..
- Fewer D, Jokela J, Rouhiainen L, Wahlsten M, Koskenniemi K, Stal L, et al. The non-ribosomal assembly and frequent occurrence of the protease inhibitors spumigins in the bloom-forming cyanobacterium Nodularia spumigena. Mol Microbiol. 2009;73:924-37 pubmed publisher..Our results demonstrate that bloom-forming N. spumigena strains produce a cocktail of enzyme inhibitors, which may explain in part the ecological success of this cyanobacterium in brackish water bodies worldwide...
- Jin X, Deng L, Li H, Zhang Z, He Q, Yang C, et al. Identification and characterization of a serine protease inhibitor with two trypsin inhibitor-like domains from the human hookworm Ancylostoma duodenale. Parasitol Res. 2011;108:287-95 pubmed publisher..These results suggested that AduTIL-1 may be involved in the survival of A. duodenale in host by targeting related digestive enzymes and neutrophil elastase. ..
- Kantyka T, Fischer J, Wu Z, Declercq W, Reiss K, Schroder J, et al. Inhibition of kallikrein-related peptidases by the serine protease inhibitor of Kazal-type 6. Peptides. 2011;32:1187-92 pubmed publisher..3nM, KLK6 with K(i)=140nM, caspase-14 with a K(i) approximating 1?M and no activity against KLK1, KLK3 and KLK11. Taken together, SPINK6 is a potent inhibitor of distinct KLKs members. ..
- Brandt I, Gerard M, Sergeant K, Devreese B, Baekelandt V, Augustyns K, et al. Prolyl oligopeptidase stimulates the aggregation of alpha-synuclein. Peptides. 2008;29:1472-8 pubmed publisher..If PO displays this activity also in vivo, PO inhibitors might have an effect on neurodegenerative disorders through a decrease in the aggregation of alpha-synuclein. ..
- Carter J, Buerke U, Rossner E, Russ M, Schubert S, Schmidt H, et al. Anti-inflammatory actions of aprotinin provide dose-dependent cardioprotection from reperfusion injury. Br J Pharmacol. 2008;155:93-102 pubmed publisher..The cardioprotective effect appears to be at least partly due to reduced PMN adhesion and infiltration with subsequently reduced myocardial necrosis and apoptosis. ..
- Sudha V, Arora N, Gaur S, Pasha S, Singh B. Identification of a serine protease as a major allergen (Per a 10) of Periplaneta americana. Allergy. 2008;63:768-76 pubmed publisher..This study was undertaken to isolate and characterize a protease from Periplaneta americana and determine its allergenicity...
- Swedberg J, Nigon L, Reid J, de Veer S, Walpole C, Stephens C, et al. Substrate-guided design of a potent and selective kallikrein-related peptidase inhibitor for kallikrein 4. Chem Biol. 2009;16:633-43 pubmed publisher..The re-engineered inhibitor was designed using a combination of molecular modeling and sparse matrix substrate screening. ..
- Li X, Zhang R, Sun R, Lan J, Zhao X, Wang J. Three Kazal-type serine proteinase inhibitors from the red swamp crayfish Procambarus clarkii and the characterization, function analysis of hcPcSPI2. Fish Shellfish Immunol. 2010;28:942-51 pubmed publisherThree Kazal-type serine proteinase inhibitors, hcPcSPI2, hpPcSPI3, and hpPcSPI4, with complete cDNA sequences, were identified from a cDNA library of the red swamp crayfish, Procambarus clarkii...
- Sidique S, Shiryaev S, Ratnikov B, Herath A, Su Y, Strongin A, et al. Structure-activity relationship and improved hydrolytic stability of pyrazole derivatives that are allosteric inhibitors of West Nile Virus NS2B-NS3 proteinase. Bioorg Med Chem Lett. 2009;19:5773-7 pubmed publisher..We now report the design, synthesis and in vitro evaluation of pyrazole derivatives that are inhibitors of WNV NS2B-NS3 proteinase with greatly improved stability in the assay medium. ..
- Ha K, Byun M, Choi J, Jeong J, Lee K, Jue D. N-tosyl-L-phenylalanine chloromethyl ketone inhibits NF-kappaB activation by blocking specific cysteine residues of IkappaB kinase beta and p65/RelA. Biochemistry. 2009;48:7271-8 pubmed publisher..These results suggest that TPCK inhibits NF-kappaB activation by directly modifying thiol groups on two different targets: Cys-179 of IKKbeta and Cys-38 of p65/RelA. ..
- Yang X, Wang Y, Lu Z, Zhai L, Jiang J, Liu J, et al. A novel serine protease inhibitor from the venom of Vespa bicolor Fabricius. Comp Biochem Physiol B Biochem Mol Biol. 2009;153:116-20 pubmed publisher..The peptide is homologous to serine protease inhibitors isolated from venoms of Anoplius samariensis and Pimpla hypochondriaca. Bicolin showed inhibitory ability against trypsin and thrombin. ..
- Flight S, Johnson L, Du Q, Warner R, Trabi M, Gaffney P, et al. Textilinin-1, an alternative anti-bleeding agent to aprotinin: Importance of plasmin inhibition in controlling blood loss. Br J Haematol. 2009;145:207-11 pubmed publisher..Based on these data, textilinin-1 merits further investigation as a therapeutic alternative to aprotinin. ..
- Ishizaki M, Tanaka H, Kajiwara D, Toyohara T, Wakahara K, Inagaki N, et al. Nafamostat mesilate, a potent serine protease inhibitor, inhibits airway eosinophilic inflammation and airway epithelial remodeling in a murine model of allergic asthma. J Pharmacol Sci. 2008;108:355-63 pubmed..These findings suggest that increased serine protease activity in the airways is involved in the development of antigen-induced allergic eosinophilic inflammation and epithelial remodeling in bronchial asthma. ..
- Ismail N, El Dine R, Hattori M, Takahashi K, Ihara M. Computer based design, synthesis and biological evaluation of novel indole derivatives as HCV NS3-4A serine protease inhibitors. Bioorg Med Chem. 2008;16:7877-87 pubmed publisher..The product was converted into 10l, which showed lower activity than the mixture of the corresponding diastereoisomers. ..
- He Y, Liu S, Lee W, Qian J, Zhang Y. Isolation, expression and characterization of a novel dual serine protease inhibitor, OH-TCI, from king cobra venom. Peptides. 2008;29:1692-9 pubmed publisher..46 x10(-8)M for trypsin and chymotrypsin, respectively. To our knowledge, it was the first report of Kunitz/BPTI serine proteinase inhibitor from snake venom that had equivalent trypsin and chymotrypsin inhibitory activities. ..
- Sales K, Masedunskas A, Bey A, Rasmussen A, Weigert R, List K, et al. Matriptase initiates activation of epidermal pro-kallikrein and disease onset in a mouse model of Netherton syndrome. Nat Genet. 2010;42:676-83 pubmed publisher..These results uncover a pathogenic matriptase-pro-kallikrein pathway that could operate in several human skin and inflammatory diseases. ..
- Aikawa N, Ishizaka A, Hirasawa H, Shimazaki S, Yamamoto Y, Sugimoto H, et al. Reevaluation of the efficacy and safety of the neutrophil elastase inhibitor, Sivelestat, for the treatment of acute lung injury associated with systemic inflammatory response syndrome; a phase IV study. Pulm Pharmacol Ther. 2011;24:549-54 pubmed publisher..The results of this study suggest the clinical usefulness of Sivelestat in this patient population. ..
- Morikawa K, Lange C, Gouttenoire J, Meylan E, Brass V, Penin F, et al. Nonstructural protein 3-4A: the Swiss army knife of hepatitis C virus. J Viral Hepat. 2011;18:305-15 pubmed publisher..This review provides a concise update on the biochemical and structural aspects of NS3-4A, its role in the pathogenesis of chronic hepatitis C and the clinical development of NS3-4A protease inhibitors. ..
- Mize G, Wang W, Takayama T. Prostate-specific kallikreins-2 and -4 enhance the proliferation of DU-145 prostate cancer cells through protease-activated receptors-1 and -2. Mol Cancer Res. 2008;6:1043-51 pubmed publisher..These data indicate that prostatic kallikreins (hK2 and hK4) directly stimulate prostate cancer cell proliferation through PAR1 and/or PAR2 and may be potentially important targets for future drug therapy for prostate cancer. ..
- Schwertz H, Carter J, Russ M, Schubert S, Schlitt A, Buerke U, et al. Serine protease inhibitor nafamostat given before reperfusion reduces inflammatory myocardial injury by complement and neutrophil inhibition. J Cardiovasc Pharmacol. 2008;52:151-60 pubmed publisher..Reduced leukocyte accumulation and complement activity seem involved in the mechanism of this cardioprotective effect. ..
- Flores M, Strawbridge J, Ciaramella G, Corbau R. HCV-NS3 inhibitors: determination of their kinetic parameters and mechanism. Biochim Biophys Acta. 2009;1794:1441-8 pubmed publisher..In the case of BILN-2061, a better fit is obtained using a one-step model, indicating that the loss of potency is due to an increase in the off-rate of the EI complex. ..
- Rimphanitchayakit V, Tassanakajon A. Structure and function of invertebrate Kazal-type serine proteinase inhibitors. Dev Comp Immunol. 2010;34:377-86 pubmed publisher..Silk moths produce KPIs to protect their cocoon from predators and microbial destruction. ..
- Bahgat M, Błazejewska P, Schughart K. Inhibition of lung serine proteases in mice: a potentially new approach to control influenza infection. Virol J. 2011;8:27 pubmed publisher..Blocking influenza A virus infection in cultured lung epithelia and in mice by the used serine protease inhibitors may provide an alternative approach for treatment of influenza infection. ..
- Myöhänen T, Tenorio Laranga J, Jokinen B, Vázquez Sánchez R, Moreno Baylach M, Garcia Horsman J, et al. Prolyl oligopeptidase induces angiogenesis both in vitro and in vivo in a novel regulatory manner. Br J Pharmacol. 2011;163:1666-78 pubmed publisher..Our results also advocate a role for Ac-SDKP in angiogenesis, and suggest that POP has a pro-angiogenic role via the release of Ac-SDKP from its precursor T?4 and POP inhibitors can block this action. ..
- Hayakawa M, Katabami K, Wada T, Sugano M, Hoshino H, Sawamura A, et al. Sivelestat (selective neutrophil elastase inhibitor) improves the mortality rate of sepsis associated with both acute respiratory distress syndrome and disseminated intravascular coagulation patients. Shock. 2010;33:14-8 pubmed publisher..The length of ICU stay of the sivelestat group was significantly shorter than that of the control group. In addition, sivelestat administration was found to be an independent predictor of survival of those patients. ..
- Gunasekera S, Miller M, Kwan J, Luesch H, Paul V. Molassamide, a depsipeptide serine protease inhibitor from the marine cyanobacterium Dichothrix utahensis. J Nat Prod. 2010;73:459-62 pubmed publisher..032 and 0.234 muM against elastase and chymotrypsin, respectively. There was no apparent inhibition of trypsin at 10 microM, the highest concentration tested. ..
- Torres Castillo J, Mondragón Jacobo C, Blanco Labra A. Characterization of a highly stable trypsin-like proteinase inhibitor from the seeds of Opuntia streptacantha (O. streptacantha Lemaire). Phytochemistry. 2009;70:1374-81 pubmed publisher..When comparing its sequence in the MEROPS database for peptidases and peptidase inhibitors, it showed 34.48% identity with a serine-proteinase inhibitor from the I15 family...
- Li Q, Nacion K, Bu H, Lin F. The complement inhibitor FUT-175 suppresses T cell autoreactivity in experimental autoimmune encephalomyelitis. Am J Pathol. 2009;175:661-7 pubmed publisher..These results argue that complement regulators, which inhibit C5a/C3a production, may have therapeutic efficacy in multiple sclerosis and in other clinical conditions in which T cells drive disease pathogenesis. ..
- Ma D, Wang Y, Yang H, Wu J, An S, Gao L, et al. Anti-thrombosis repertoire of blood-feeding horsefly salivary glands. Mol Cell Proteomics. 2009;8:2071-9 pubmed publisher..The extreme diversity of horsefly anti-thrombosis components also reveals the anti-thrombosis molecular mechanisms of the traditional Eastern medicine insect material. ..
- Jalkanen A, Hakkarainen J, Lehtonen M, Venäläinen T, Kääriäinen T, Jarho E, et al. Brain pharmacokinetics of two prolyl oligopeptidase inhibitors, JTP-4819 and KYP-2047, in the rat. Basic Clin Pharmacol Toxicol. 2011;109:443-51 pubmed publisher..KYP-2047 is a brain-penetrating, potent and long-acting PREP inhibitor; thus, it represents a convenient pharmacological tool for assessing the potential of PREP as a drug target. ..
- Ascenzi P, Gianni S. Functional role of transient conformations: Rediscovering "chronosteric effects" thirty years later. IUBMB Life. 2013;65:836-44 pubmed publisher..Here, some recent results on the folding and function of proteins are reported on the light of chronosteric effects. ..
- Xu C, Deng F, Mao Z, Zhang J, Wang H, Wang J, et al. The interaction of the second Kunitz-type domain (KD2) of TFPI-2 with a novel interaction partner, prosaposin, mediates the inhibition of the invasion and migration of human fibrosarcoma cells. Biochem J. 2012;441:665-74 pubmed publisher..The results of the present study revealed that TFPI-2 interacts with PSAP, which may play an important role in the physiology and pathology of diseases such as cancer. ..
- Bourliere M, Khaloun A, Wartelle Bladou C, Oules V, Portal I, Benali S, et al. Future treatment of patients with HCV cirrhosis. Liver Int. 2012;32 Suppl 1:113-9 pubmed publisher..First generation protease inhibitors plus PR appear to be a new step forward in the management of HCV genotype 1 patients with cirrhosis. ..
- Xu S, Li H, Shao X, Fan C, Ericksen B, Liu J, et al. Critical effect of peptide cyclization on the potency of peptide inhibitors against Dengue virus NS2B-NS3 protease. J Med Chem. 2012;55:6881-7 pubmed publisher..In addition, this work highlights the critical effect of peptide cyclization on the potency of oligopeptide inhibitors against DENV protease, which may advance the design of peptide inhibitors for homologous virus proteases. ..
- Craik C, Shahian T. A screening strategy for trapping the inactive conformer of a dimeric enzyme with a small molecule inhibitor. Methods Mol Biol. 2012;928:119-31 pubmed publisher..This methodology can be applicable to other systems where an alpha helical moiety plays a dominant role at the interaction site of interest, and in vitro assays to monitor function are in place. ..
- Goodarzi M, Bora A, Borota A, Funar Timofei S, Avram S, Heyden Y. Modeling of 2-pyridin-3-yl-benzo[d][1,3]oxazin-4-one derivatives by several conformational searching tools and molecular docking. Curr Pharm Des. 2013;19:2194-203 pubmed..We conclude that OMEGA software generates the most representative conformers to model the protein-ligand interactions. ..
- Karpuzoglu E, Gogal R, Ansar Ahmed S. Serine protease inhibitor, 4-(2-aminoethyl)-benzene sulfonyl fluoride, impairs IL-12-induced activation of pSTAT4?, NF?B, and select pro-inflammatory mediators from estrogen-treated mice. Immunobiology. 2011;216:1264-73 pubmed publisher..These findings provide a new understanding of inflammation and inhibition of serine proteases has important implications for designing novel therapeutic strategies for a broad range of inflammatory diseases. ..
- Campos M, Kueppers F, Stocks J, Strange C, Chen J, Griffin R, et al. Safety and pharmacokinetics of 120 mg/kg versus 60 mg/kg weekly intravenous infusions of alpha-1 proteinase inhibitor in alpha-1 antitrypsin deficiency: a multicenter, randomized, double-blind, crossover study (SPARK). COPD. 2013;10:687-95 pubmed publisher..The effect of this dosing regimen on slowing and/or preventing emphysema progression in subjects with AATD warrants further investigation. ..
- Siles R, Kawasaki Y, Ross P, Freire E. Synthesis and biochemical evaluation of triazole/tetrazole-containing sulfonamides against thrombin and related serine proteases. Bioorg Med Chem Lett. 2011;21:5305-9 pubmed publisher..Thrombin binding affinity of the same compound was determined by ITC and demonstrated that the binding of this new triazole-based scaffold is enthalpically driven, making it a good candidate for further development. ..
- Zhou L, Ruan M, Cai Q, Liu G, Sun L, Su W, et al. Purification, characterization and cDNA cloning of a trypsin from the hepatopancreas of snakehead (Channa argus). Comp Biochem Physiol B Biochem Mol Biol. 2012;161:247-54 pubmed publisher..5-9.5 and below 45°C. The enzymatic activity was strongly inhibited by serine proteinase inhibitors, such as MBTI, Pefabloc SC, PMSF, LBTI and benzamidine...
- Sidhu P, Abdel Aziz M, Sarkar A, Mehta A, Zhou Q, Desai U. Designing allosteric regulators of thrombin. Exosite 2 features multiple subsites that can be targeted by sulfated small molecules for inducing inhibition. J Med Chem. 2013;56:5059-70 pubmed publisher..The results suggest that multiple avenues are available within exosite 2 for inducing thrombin inhibition. ..