Disease relevance of Compound

• A Novel Molecular Targeting Compound as K-samII/FGF-R2 Phosphorylation Inhibitor, Ki23057, for Scirrhous Gastric Cancer [1].
• Compounds II and IV were active against all three experimental tumors; both compounds produced significant tumor regression in the human breast tumor xenograft and Compound IV caused tumor regression in the human lung tumor xenograft [2].
• These results provide evidence that the i.v. injection of Compound 48/80 or pilocarpine causes: (a) hyperglycemia; (b) depletion of hepatic glycogen, and (c) a concomitant decrease in the number of Falck-Hillarp-positive mast cells [3].
• The cytotoxic activities of three new synthetic catechol analogues, beta-[(p-hydroxyphenyl)amino]alanine (Compound 1), N delta-(p-hydroxyphenyl)ornithine (Compound 2), and N delta-(m-hydroxyphenyl)ornithine (Compound 3), were determined against 10 human melanoma and 5 nonmelanoma cell lines [4].
• alpha-(N-Acetylaminomethylene)succinic acid hydrolase (Compound A hydrolase, EC 3.5.1-) and alpha-hydroxymethyl-alpha'-(N-acetylaminomethylene)succinic acid hydrolase (Compound B hydrolase, EC 3.5.1-) were purified to homogeneity from Pseudomonas MA-1 and Arthrobacter Cr-7, respectively [5].

Psychiatry related information on Compound

• In an in vivo experiment, nociceptin significantly inhibited a light-induced (300 lux, 1 h) phase delay of locomotor activity rhythms, and this effect was inhibited by Compound B [6].
• Complexes , also catalyzed the same reaction but required heating at 80 degrees C and longer reaction times compared with . Compound is inactive [7].
• Also, a Compound Model is proposed, with three distinctive patterns of the parent-child relationship that impact on posttraumatic symptomatology in young children [8].

High impact information on Compound

• The penetrance and severity of the defects in Egfrwa2/wa2 mice are enhanced by heterozygosity for a targeted mutation of exon 2 of Ptpn11 (ref. 3). Compound (Egfrwa2/wa2:Ptpn11+/-) mutant mice also show premature lethality [9].
• Dichloroacetylene, 2-bromo-2-chloro-1,1-difluoroethylene, and Compound A form glutathione S-conjugates that undergo hydrolysis to cysteine S-conjugates and bioactivation of the cysteine S-conjugates by renal cysteine conjugate beta-lyase to give nephrotoxic metabolites [10].
• Very similar lesions could also be induced by intradermal injection of Compound 48/80, thus suggesting a central role in the reaction for the mast cell or basophil [11].
• The mast cells possessed characteristic dense granules, which stained metachromatically, but did not release histamine on exposure to Compound 48/80 [12].
• In the present study, we found that Compound A (CpdA), a plant-derived phenyl aziridine precursor, although not belonging to the steroidal class of GR-binding ligands, does mediate gene-inhibitory effects by activating GR [13].

Chemical compound and disease context of Compound

• Two NAD+-dependent, highly specific pyridine-5-aldehyde dehydrogenases, 5-formyl-3-hydroxy-2-methylpyridine-4-carboxylic-acid (Compound 1) dehydrogenase and isopyridoxal dehydrogenase, were purified to homogeneity from Pseudomonas MA-1 and Arthrobacter Cr-7, respectively [14].
• VP4 Protein from Human Rhinovirus 14 Is Released by Pressure and Locked in the Capsid by the Antiviral Compound WIN [15].
• (E)-(S)-4-((S)-2-{3-[(5-methyl-isoxazole-3-carbonyl)-amino]-2-oxo-2H-pyridin-1-yl}-pent-4-ynoylamino)-5-((S)-2-oxo-pyrrolidin-3-yl)-pent-2-enoic acid ethyl ester (Compound 1) is a novel, irreversible inhibitor of human rhinovirus (HRV) 3C protease {inactivation rate constant (Kobs/[I]) of 223,000 M-1s-1} [16].
• This compound reversed the GBL-induced DOPA synthesis (ED50 values of 5.1 mumol/kg p.o.) and inhibited the APO induced stereotypy (ED50 values of 0.6 mumol/kg p.o.). Compound 28 induced catalepsy at 10 times higher dose than that required for the antagonism of APO-induced stereotypy (ED50 value of 7.8 mumol/kg p.o.) [17].
• Pretreatment of Compound X (a specific CCR3 antagonist), pertussis toxin, genistein, and wortmannin reduced the MAP kinase phosphorylation and cytokine production [18].

Biological context of Compound

• We used an intracellular polyglutamine protein aggregation assay based on fluorescence resonance energy transfer (FRET) to identify inhibitors of androgen receptor (AR) aggregation in three libraries of biologically active small molecules: the Annotated Compound Library, the NINDS Custom Collection and a kinase inhibitor collection [19].
• Alternatively, the physiological substrate H2O2 brings both protons to the active site of HRP, and Compound I is subsequently formed via rearrangement of the proton from the proximal to the distal oxygen atom of the bound peroxide [20].
• The kinetics of formation and breakdown of the putative active oxygenating intermediate in cytochrome P450, a ferryl-oxo-(pi) porphyrin cation radical (Compound I), have been analyzed in the reaction of a thermostable P450, CYP119, with meta-chloroperoxybenzoic acid (m-CPBA) [21].
• The inhibition of microsomal G-6-P transport by compound A was associated with inhibition of the rate of glucose output from rat hepatocytes incubated in the presence of 25 nmol/l glucagon (IC50 approximately 320 nmol/l.) Compound A (1 micromol/l) also inhibited the basal rate of glucose production by rat hepatocytes by 47% [22].
• Furthermore, Compound A and LTB4 induced chemotaxis in primary mouse keratinocytes [23].

Anatomical context of Compound

• From stopped flow data, the oxidation was concluded to occur by way of two-electron transfer and the rate constant for the reaction of thyroid peroxidase Compound I with thyroglobulin was estimated to be 1.0 X 10(7) M-1 s-1 [24].
• Cultured rat embryonic skin fibroblasts phagocytosed rat mast cell granules added to the medium or released from co-cultured mast cells by rabbit anti-rat IgE or Compound 48/80 [25].
• Using a fluorogenic peptide containing an amyloid precursor protein gamma-secretase cleavage site and Compound E, a specific gamma-secretase inhibitor, we found high levels of gamma-secretase activity in renal brush border membrane vesicles [26].
• Rat eosinophils have been showed to respond chemotactically to the supernatant from mast cells which have been disrupted by freezing and thawing and from mast cells which have been specifically degranulated by Compound 48/80 or by antigen challenge or sensitised cells [27].
• CPPD crystals also activated the ERK1 and ERK2 forms of MAP kinase (wortmannin insensitive), PKC (Compound 3 sensitive) and protein kinase B (wortmannin sensitive) in neutrophils [28].

Associations of Compound with other chemical compounds

• In the reaction between equimolar amounts of horseradish peroxidase and chlorite, the native enzyme is oxidized directly to Compound II (Hewson, W.D., and Hager, L.P. (1979) J. Biol. Chem. 254, 3175-3181) [29].
• Formation of the ferryl (FeIV=O) porphyrin radical cation known as Compound I in the reaction of horseradish peroxidase (HRP) with H2O2 is catalyzed by His-42, a residue that facilitates the binding of H2O2 to the iron and subsequent rupture of the dioxygen bond [30].
• The highly pH-dependent chemistry of Compound II can be readily demonstrated by the reduction of Compound I, with ferrocyanide at acidic, neutral, and alkaline pH values [29].
• Resonance Raman spectra of ferrous and ferric cytochrome c peroxidase and Compound ES and their pH dependences were investigated in resonance with Soret band [31].
• Spectral simulation based on Gaussian analyses and visible bands indicate that H2O2- and TBHP-induced intermediates' spectra of the wild type are close to that of Compound I of horseradish peroxidase, whereas TBHP- and CHP-induced intermediates' spectra of the mutants are close to that of Compound II of horseradish peroxidase [32].

Gene context of Compound

• In contrast, LPO Compound II is unstable and decays within seconds to ground state, suggesting that SCN- may serve as a substrate for Compound II [33].
• MPO and EPO Compound II is relatively stable and decays gradually within minutes to ground state upon H2O2 exhaustion [33].
• We previously found that 2-(2-mercaptoethanol)-3-methyl-1,4-napthoquinone or Compound 5 (Cpd 5), is a Cdc25A protein phosphatase inhibitor and causes prolonged, strong ERK phosphorylation which is triggered by epidermal growth factor receptor (EGFR) activation [34].
• Preincubation with alphaCGRP(8-37) (10(-7) -10(-5) M) and a novel nonpeptide CGRP antagonist "Compound 1" (WO98/11128) (10(-7)-10(-5) M) caused a dose-dependent rightward shift of the concentration-response curves for alphaCGRP with pA(2) values of 7.0 and 7.1, respectively [35].
• This was accomplished by treating mice genetically deficient in either LXRalpha or LXRbeta with an agonist with equal potency for both isoforms (Compound B) or a synthetic agonist selective for LXRalpha (Compound A) [36].

Analytical, diagnostic and therapeutic context of Compound

• By using cDNA array analysis, we have identified downstream genes whose expression is altered by Compound 2 in human cancer cells [37].
• The affinity of resting (ferric) KatG[S315T] for INH, measured using isothermal titration calorimetry, was greatly reduced compared with wild-type KatG, as were rates of reaction of Compound I with the drug [38].
• Using primary cultures of adult rat hepatocytes that are in G0/G1 phase until stimulated into DNA synthesis by epidermal growth factor, we found that 2-(2-mercaptoethanol)-3-methyl-1,4-naphthoquinone or Compound 5 (Cpd 5) inhibited hepatocyte DNA synthesis and PTP activity in cell culture and in vivo after a two-thirds partial hepatectomy [39].
• In addition, crystals were analyzed by UV-vis absorption and electron paramagnetic resonance spectroscopies before and after data collection to determine the state of the Fe(IV) center and the cationic Trp191 radical formed in Compound I [40].
• We used peptide mapping by HPLC, Edman sequencing, and matrix-assisted time-of-flight (MALDI-TOF) mass spectrometry to identify the site of interaction with radiolabeled Compound 1 [41].

References