Activator-inhibitor model

Nakao and Mikhailov [316] performed numerical simulations of an activator-inhibitor model, namely the Mimura-Murray model, on a large array, namely a Barabasi-Albert scale-free network with 1000 nodes and mean degree of 20 ... 

We shall then call species x the activator, since making more of it activates the production of still more. Species y is referred to as the inhibitor. A model of the form of eq. (14.1), with one positive and one negative Jacobian element, is called an activator—inhibitor model. Models of this type have played a key role in the investigation of Turing patterns. 

We wish to show how, by adding diffusion terms and the complexation of the activator species (iodide in this case) by an immobile agent, such as starch, Turing patterns can be generated from an activator-inhibitor model like eqs. (14.32) and (14.33). We shall analyze a more general version of the problem, because its solution will lead us to a systematic approach to designing new svstems that exhibit Turing pattern formation. 

Researchers at Combio and Arpida have reported a series of isoxazole-3-hydroxamic acids as PDF inhibitors [109], Molecular modelling studies predict that the aryl substituent of isoxazole (37) binds into the SF pocket and that the oxygen atom of the isoxazole is involved in a H-bonding interaction with Ile-44 in E. coli PDF, similar to the PF carbonyl of actinonin. None of the inhibitors reported has sub-micromolar inhibitory activity against E. coli or S. aureus PDF. Not surprisingly, these moderately active inhibitors also lack antibacterial activity. 

Andrews, P.R., Carson, J.M., Caselli, A., Spark, M.J., Woods, R. Conformational analysis and active site modelling of angiotensin-converting enzyme inhibitors. /. Med. Chem. 1985, 28(3), 393-399. 

Yet another indole-based lipoxygenase inhibitor has shown activity in models of inflammatory bowel disease. The starting benzylaniline (23-3) can speculatively be obtained by alkylation on the phenol oxygen in (23-2) with 2-bromomethyl-quinoline (23-1). The customary diazotisation reduction sequence then affords the... 

Peterson, Y. K., Wang, X. S., Casey, P. J., Tropsha, A. (2009) Discovery of geranylgeranyltransferase-I inhibitors with novel scaffolds by the means of quantitative structure-activity relationship modeling, virtual screening, and experimental validation. J Med Chem 52, 4210-4220. 

Iwanowicz EJ, Lau WF, Lin J, Roberts DGM, Seiler SM. Retro-binding tripeptide thrombin active inhibitors discovery, synthesis and molecular modeling. J Med Chem 1994 37 2122-2124. 

A study using a rat model of sepsis induced by cecal ligation and perforation (CLP) showed that PMXB hemoperfusion performed 24 hours after the CLP procedure reduced plasminogen activator inhibitor -1 expression in the lung, and apoptosis in renal tubular cells (Ito et al., 2009). 

Figure 8-11. PAL active site model (residues shown in black) and the mode of PheP R, 2 inhibitor binding. The closest atomic contacts with PAL residues are marked as dashed lines...

As noted above, our analysis suggests that a satisfactorily precise description of this particular set of PAL inhibitors binding is provided by the PAL active site model encompassing four out of the initial number of six amino acid residues, especially... 

As the H+, K+-ATPase inhibition is associated with the modification of mer-capto groups in the enzyme, the disulfide adduct (ESSR) can be considered as a model of the enzyme-inhibitor complex, and the sulfenamide, or possibly the sulfenic acid (C), formed from omeprazole can be considered to be the active inhibitor, which binds covalently to cysteine residues of the H+, K+-ATPase. 

Levi M, Biemond BJ, VanZonneveld AJ et al. (1992) Inhibition of plasminogen activator inhibitor-1 activity results in promotion of endogenous thrombolysis and inhibition of thrombus extension in models of experimental thrombosis. Circulation 85 305-312... 

Sidelmann UG, Cornett C, Tjornelund J, Hansen SH (1996) A comparative study of precision cut liver slices, hepatocytes and liver microsomes from the Wistar rat using metronidazole as a model substance. Xenobiotica 26 709-722 Stratford RE, Clay MP, Heinz BA et al. (1999) Application of Oral Bioavailability Surrogates in the Design of Orally Active Inhibitors of Rhinovirus Replication. J Pharm Sci 88 747-753... 

F ure 3.29. The use of active-site models in the Active Analog Approach. The structure shown is one of a series of ACE inhibitors analyzed. The thick gray lines are noncovalent interactions between the inhibitor and active-site points in the enzyme. The dashed lines correspond to the six interatomic distances monitored for each of the inhibitors analyzed... 

The following quotation [from the original research report (81 )on the design of captopril] predicted the great promise of SBDD "The studies described above exemplify the great heuristic value of an active-site model in the design of inhibitors, even when such a model is a hypothetical one."... 

Eitzman, D. T., Krauss, J. C., Shen, T. L., Cui, J. S. and Ginsburg, D. (1996). Lack of plasminogen activator inhibitor-1 effect in a transgenic mouse model of metastatic melanoma. Blood 87,4718 722. 

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