Identifying Inhibitors

Look at the ingredients listed on packages of cereals and crackers in your kitchen. 

Note the preservatives listed. These are chemical inhibitors. 

Compare the date on the box with the approximate date the box was purchased to estimate shelf life. 

What is the average shelf life of these products  

Surface Area Affects Rate The exposed surface area of reactant particles also affects how fast the reaction can occur. You can quickly start a campfire with small twigs, but starting a fire with only large logs would probably not work. 

---

Miscellaneous Identified Inhibitors. 3-Acetyl-6-methoxy-benzaldehyde is present in the leaves of the desert shrub Encelia farinosa. It is apparently leached from the leaves and washed into the soil by rain. Concentrations of approximately 0.5 mg. per gram of dried leaf material have been measured. In sand culture studies, growth of tomato seedlings was inhibited by 50 p.p.m. while 115 p.p.m. reduced growth by 50% (53). A concentration of 250 p.p.m. killed the test plants within one day. The structure was confirmed by synthesis, and the synthetic material was shown to be as active as the natural product (54). Derivatives were also prepared in which a cyano, nitro, or amino group was substituted for the aldehyde moiety. The amino derivative was reported to be the most highly toxic. 

ATP-STD NMR is described as a simple, cost-effective and robust assay that can be used to identify inhibitors of virtually any nucleotide-binding target. 

A Forward Chemical Genetic Screen to Identify Inhibitors of... 

In the following sections, we present protocols that can be used to set up screenings specifically aimed at identifying inhibitors of these activities. 

Our screen has the potential to identify inhibitors of cap-dependent initiation, IRES-mediated initiation, and translation elongation or termination. One assay to identify initiation inhibitors from hits obtained in the primary screen is to assess the ability of a given compound to prevent 48S and/or 80S initiation complex formation on a capped mRNA and on the HCV IBJ3S. Because initiation complexes are formed more efficiently in RRL than in... 

Peterson, J. R., Lebensohn, A. M., Pelish, H. E., and Kirschner, M. W. (2006). Biochemical suppression of small-molecule inhibitors A strategy to identify inhibitor targets and signaling pathway components. Chem. Biol. 13, 443—452. 

Since- the maximum rate is not affected significantly, this identifies inhibitor as noncompetitive. 

The discovery of inhibitors of fibrillogenesis has been hampered by the complexity of the folding pathway, the presence of mixed populations of aggregates, and the lack of sensitive markers of each oligomeric species.40 Screening assays based on thioflavin-S fluorescence or Congo-red absorbance have been used to identify inhibitors of aggregation of synthetic Af peptide. The reported compounds suffer from relatively low potency (effective at <10 pM) and "flat" SARs." 43... 

Min, D.H., Tang, W.J., Mrksich, M. Chemical screening by mass spectrometry to identify inhibitors of anthrax lethal factor. Nat. Biotcchnol. 2004, 22, 717-723. 

Tethering with extenders was also used to identify inhibitors to the antiinflammatory target caspase-1 [28, 29]. In this case, one of the same extenders previously designed for caspase-3 selected an entirely different set of fragments. This is consistent with different substrate peptide sequence preferences WEHD for caspase-1 vs DEVD for caspase-3 [30]. 

Chemo- genomics BaC Use information on targets to identify specific modulators, then look for phenotypes Compounds/drugs for novel targets Select targets Identify inhibitor Broadly assay for phenotypes... 

Kau, T. R., Schroeder, F., Ramaswamy, S., et al. (2003) A chemical genetic screen identifies inhibitors of regulated nuclear export of a forkhead transcription factor in PTEN deficient tumor cells. Cancer Cell 4, 463-467. 

S Roychoudhury, SE Blondelle, SM Collins, MC Davis, HD McKeever, RA Houghten, CN Parker. Use of combinatorial library screening to identify inhibitors of a bacterial two-component kinase. Molecular Diversity 4 173-182, 1998. 

---