Disease relevance of Inhibitor 3

• The spinal cord ischemic tolerance induced by HBO preconditioning was attenuated when a CAT inhibitor, 3-amino-1,2,4-triazole,1 g/kg, was administered intraperitoneally 1 h before ischemia [1].
• A protein-ligand X-ray crystal structure of inhibitor 3-bound HIV-1 protease (1.35 A resolution) revealed extensive interactions in the HIV protease active site including strong hydrogen bonding interactions with the backbone [2].
• To investigate this, we have attempted to further characterise the suppression of bone formation by the potent bone resorption inhibitor 3-amino-1-hydroxypropylidine-1-bisphosphonate (AHPrBP) in ovariectomised adult female rats [3].
• 6. Pretreatment with MK886 (5-lipoxygenase-activating protein inhibitor, 3 mg kg(-1)), CP 105696 (LTB(4) receptor antagonist; 3 mg kg(-1)) or dexamethasone (0.5 mg kg(-1)) inhibited the hypersensitivity from 1 to 5 h [4].
• (Mono)ADP-ribosylation experiments with crude membranes in the presence of the (poly)ADP-ribosyltransferase inhibitor, 3-amino-benzamide, resulted in the detection of a cholera toxin substrate of 52 kDa and two pertussis toxin substrates, 33 and 39 kDa [5].

High impact information on Inhibitor 3

• Tissue metalloproteinase inhibitor 3, clusterin, vitronectin, and serum albumin were the most common proteins observed in normal donor drusen whereas crystallin was detected more frequently in AMD donor drusen [6].
• Structural basis for the inhibition of porcine pepsin by Ascaris pepsin inhibitor-3 [7].
• Increasing the stationary concentration of UVB-induced DNA breaks by inhibition of repair in the presence of the adenosine diphosphoribose (ADPR)-transferase inhibitor 3-amino-benzamide suppressed the induction of c-fos [8].
• However, the serpin PA inhibitory activity in extracts of both the normal brain and tumor is of the protease nexin I/PA inhibitor 3 type [9].
• Herein, we show that inhibitor 3, in contrast to GM6001, had no effect on pro-MMP-2 activation by MT1-MMP [10].

Chemical compound and disease context of Inhibitor 3

• This study examined the effectiveness of the cyclooxygenase/lipoxygenase inhibitor 3-amino-1-[m-(trifluoromethyl)phenyl]-2-pyrazoline (BW755C) in preventing the toxicity induced in male F-344 rats by methyl chloride (MeCl) [11].

Biological context of Inhibitor 3

• Furthermore, inhibitor 3 reduced tumor cell migration and invasion in vitro [10].
• However, an important role for active infection is demonstrated by the additional delay in apoptosis with intracellular growth and the refractory abrogation of this response by the p38 MAPK inhibitor 3 to 6 h after neutrophil infection [12].
• Heat treatment of E. chaffeensis or the addition of monodansylcadaverine, a transglutaminase inhibitor, 3 h prior to infection inhibited the up-regulation of TfR mRNA [13].
• Inhibitor 3 lowered blood pressure in sodium-deficient dogs, with in vivo potency 19 times that shown by 1, in close agreement with the relative in vitro potencies [14].
• The effects of the dual cyclooxygenase-lipoxygenase inhibitor 3-amino-1-(m[trifluoromethyl]phenyl)-2-pyrazoline (BW755C) (10 mg/kg, p.o., b.i.d.) on renal blood flow, glomerular filtration rate (GFR), and eicosanoid production were examined in anesthetized dogs that had undergone unilateral renal allotransplantation [15].

Anatomical context of Inhibitor 3

• Two separate signal transducer and activator of transcription proteins regulate transcription of the serine proteinase inhibitor-3 gene in hepatic cells [16].
• The TF/FVIIa inhibitor 3-amino-5-[1-[2-([4-[amino(imino)methyl]benzyl]amino)-2-oxoethyl]-3-chloro-5-(isopropylamino)-6-oxo-1,6-dihydropyrazin-2-yl]benzoic acid dihydrochloride (PHA-927F) was fully effective in prevention of thrombosis-induced vessel occlusion at a dose of 400 microg/kg/min, i.v., in the arterial vasculature (femoral artery) [17].
• The heart and aortic arch were carefully removed and retroinfused with enzyme solution (1 mg/ml collagenase type I, 0.5 mg/ml soybean trypsin inhibitor, 3% BSA, and 2% antibiotics) through the aortic arch [18].
• Protein phosphatase-1 inhibitor-3 is co-localized to the nucleoli and centrosomes with PP1gamma1 and PP1alpha, respectively [19].
• Genome-wide expression profiling of fetal membranes reveals a deficient expression of proteinase inhibitor 3 in premature rupture of membranes [20].

Associations of Inhibitor 3 with other chemical compounds

• However, oxidative protein modifications were also observed, including apparent crosslinked species of tissue metalloproteinase inhibitor 3 and vitronectin, and carboxyethyl pyrrole protein adducts [6].
• Clinical pharmacokinetic and pharmacodynamic studies with the nonclassical antifolate thymidylate synthase inhibitor 3, 4-dihydro-2-amino-6-methyl-4-oxo-5-(4-pyridylthio)-quinazolone dihydrochloride (AG337) given by 24-hour continuous intravenous infusion [21].
• The three most active compounds in this family were 13-membered-ring glutamine-derived inhibitor 3, 14-membered-ring diaminopropionic acid derived inhibitor 6, and 13-membered-ring diol 9 (IC50 0.61, 0.59, 0.65 microM, respectively) [22].
• The optimum hybrid inhibitor 3 is 37-fold more potent and 31-fold more selective than tacrine in vitro [23].
• Administration of p-chlorophenylalanine (PCPA, 300 mg/kg, i.p.), a tryptophan hydroxylase inhibitor, 3 days before the dialysis experiments reduced the hippocampal 5-HT content to 30% of that in saline-treated rats, but did not affect basal ACh release in the hippocampus [24].

Gene context of Inhibitor 3

• However, when the small bowel juice had been pre-incubated with soybean trypsin inhibitor 3 g/l, casein 5 g/l or lactalbumin 30 g/l, the hydrolysis of PSTI diminished so that 95%, 32%, and 33% respectively, now eluted in the characteristic position of free (i.e. intact and not bound to an enzyme) PSTI [25].
• We describe herein a set of mechanism-based inhibitors that show high selectivity to gelatinases and MMP-14 (inhibitor 3) and to only MMP-2 (inhibitors 5 and 7) [10].
• The results show that (1) the dimericity of BS-RNase is essential for its full cytotoxic action; (2) the role of the dimeric structure in the antitumor activity is that of making the enzyme insensitive to the cytosolic RNase inhibitor; (3) a RNase may not be completely insensitive to cRI to exploit a full cytotoxic potential [26].
• Activation of the rat serine proteinase inhibitor 3 gene by interferon gamma via the interleukin 6-responsive element [27].
• The gene for cyclin-dependent protein kinase inhibitor 3 (CDKN3) was identified as a potential candidate gene in a differential display experiment [28].

Analytical, diagnostic and therapeutic context of Inhibitor 3

• Immunohistochemistry demonstrated decreased proteinase inhibitor 3 protein expression in preterm premature rupture of membranes [20].
• Gene expression, measured by Affymetrix microarray analysis, indicates that in the BMRC of Ikaros-null mice, there is significant up-regulation of SMADs 6 and 7, serine protease inhibitor 3, and immediate-early protein 3 (IER3), all proteins that play a modulating role in apoptosis [29].
• To prevent ovariectomy from stimulating bone turnover, and hence complicating the interpretation of changes in bone formation, animals were also given the resorption inhibitor 3-amino-1-hydroxypropylidene-1-bisphosphonate [30].
• However, after treatment with neutrophil elastase inhibitor, 3 of 10 rats in the I/R group, survived more than 7 days [31].

References