Receptor fitting

Agonists are dru that bind with a receptor to produce a therapeutic response Dru that bind only partially to the receptor will most probably have some, although slight, therapeutic response Figure 1-3 identifies the different drug-receptor interactions. Partial agonists are dm that have some drug receptor fit and produce a response but inhibit other responses. 

If we assume that those peculiarities of the toxin which cause their distribution are localized in a special group of the toxin molecules and the power of the organs and tissues to react with the toxin are localized in a special group of the protoplasm, we arrive at the basis of my side chain theory. The distributive groups of the toxin I call the haptophore group and the corresponding chemical organs of the protoplasm the receptor. . .. Toxic actions can only occur when receptors fitted to anchor the toxins are present. 

Volm M, Koomagi R, Mattern J. Prognostic value of vascular endothelial growth factor and its receptor Fit-1 in squamous cell lung cancer. Int J Cancer 1997 74 64-68. 

VEGF binds to endothelial receptors Fit-1 and Flk-1 to activate a signal transduction cascade (Fig. 4). Neutralizing antibodies to Flk-1 inhibit angiogenesis (21). This inhibition of angiogenesis is most effective in glioblastoma xenographs and also reduces tumor... 

Chintalgattu, V., Nair, D. M., and Katwa, L. C. 2003. Cardiac myofibroblasts a novel source of vascular endothelial growth factor (VEGF) and its receptors Fit-1 and KDR. J. Mol. Cell. Cardiol. 35 277-286. 

BAY 43-9006 (Sorafenib Bayer/Onyx Pharmaceuticals, Emeryville, CA) is a biaryl urea that inhibits Raf-1 kinase activity in vitro with IC50 value of 6nM, and B-Raf with IC50 value of 22 nM (25). This compound also inhibits some receptor tyrosine kinases, which include VEGF receptor family members, PDGF receptor. Fit, and c-Kit, at close to the same potency. 

A consistent feature exists in all of these models, in that, for a good odorant/receptor fit, each model requires a polar group in the odorant that can form a hydrogen bond or similar interaction with a donor site in the receptor and the rest of the fit is determined by a spatial match with the shape of the... 

Shihab FS, Bennett WIVl,Yi H, AndohTF. Expression of vascuiar endotheiiai growth factor and its receptors Fit-1 and KDR/Fik-1 in chronic cyciosporine nephrotoxicity.Transpiantation 2001 72 164-168. 

Vedani A, Zbinden P. Quasi-atomistic receptor modeling A bridge between 3D QSAR and receptor fitting. Pharmaceut acta Helv 1998 73 11-8. 

When considering in vivo activities, the difference in activity observed for the two enantiomers is neither always and nor exclusively the result of the quality of the ligand-receptor fit. It must be kept in mind that in vivo the pharmacokinetic processes (ADME) may account for the observed difference in activity. The interpretation of pharmacological data obtained from in vivo assays should thus be questioned and does not allow anticipating the quality of the ligand-receptor interaction. 

Receptors for IGF peptides have also been described in a wide variety of other cells and tissue preparations, of which liver (K3, M13), adipocytes (Zl), chondrocytes (P4) and chondrosarcoma (A9), fibroblasts (A4), pituitary and neural tissues (G6, S7), erythrocytes (P12) and lymphocytes (Rll), Sertoli cells (B31), and arterial smooth muscle (P3) represent a cross-section. In general it appears that the structurally defined (M7) type-I and type-II growth factor receptors fit satisfactorily into two functional classes. The type-I receptor has a high affinity for SM-C/IGF-I, a somewhat lower (but sometimes equal) affinity for IGF-II, and low affinity for insulin (O.I to 1% of that for SM-C/IGF-I). The type-II receptor has a high affinity for IGF-II, low to moderate affinity for SM-C/IGF-I, and does not interact at all with insulin. A type-III receptor for IGF-II has recently been postulated to exist on IM-9 lymphocytes (H2I), but whether this will eventually turn out to be a distinct structural class, or simply the result of interactions of IGF-II tracer with IGF-I, IGF-II and insulin receptors, remains to be established. 

Although the majority of receptors fit into the classes described previously, there are some receptors that do not. Smaller classes of receptors include receptor... 

C. Some drug-receptor fit. Slight therapeutic response possible. 

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