Affinity profile

Mignat C, Wille U, Ziegler A. (1995). Affinity profiles of morphine, codeine, dihydrocodeine, and their glucuronides at opioid receptor subtypes. Life Sci. 56(10) 793-99. 

Mutschler, E. Affinity profiles of hexahydro-sila-difenidol analogues at muscarinic receptor subtypes. 

Due to the numerous indications for these type of drugs a large number of compounds have been introduced into therapy. Differences between these drugs concern their affinity profile towards the Pi-and j82-adrenoceptors, the lipophilicity and the ability to partially activate the receptor (intrinsic sympathomimetic activity, ISA). One isomer of the racemic mixture of labetalol and carvedilol are a-blocker as well. Although this might be therapeutically useful in the treatment of conditions like hypertension and heart failure, there is no real evidence for a contribution of this property to the overall beneficial effect of these compounds. 

The plot dnp versus dphar for all (119 x 118)/2 kinase pairs (/, j) shows no correlation between the two metrics (Fig. 9.1d). However, when the highly promiscuous affinity-dominant staurosporine is incorporated to the affinity profile [14] and the affinity-based distance matrix is recalculated ( dps = pseudopharmacological distance), a good correlation (R2 = 0.875) between dps and dnp is obtained (Fig. 9.1e). This correlation reveals that promiscuity, the dominant affinity trait when staurosporine is incorporated, is fostered by targeting accessible nonpolar moieties, in turn, a highly conserved feature of protein interfaces [21], The strong correlation shown in Fig. le implies that staurosporine should bind mainly through hydrophobic contacts, as it is indeed the case in its PDB complexes [22],... 

Table 10.1 Predicted and experimental affinity profiles for the clean version of kinase inhibitor EKB-569...

Fig. 10.2 Affinity profile of the redesigned EKB-569 prototype inhibitor. High-throughput screening at 10 mM EKB-569 (blue) and prototype (red) over a battery of 228 human kinases displayed in a T7-bacteriophage-expressing library. Hit values are reported as percentage-bound kinase. Reprinted from [37], copyright 2008 with permission from Elsevier...

REUBI, J.C., et al., Affinity profiles for human somatostatin receptors subtypes SST1-SST5 of somatostatin radiotracers selected for scintigraphic and radio-therapeutic use, Eur. J. Nucl. Med. 27 (2000) 273-282. 

DOTATATE, thereby demonstrating that the presence of metal does not interfere with the receptor affinity profile. 

C. Assessing affinity profiles using parallel in sUko screening... 

Figure 3. Structures and affinity profiles (pA2 values) of (R)- and (S)-enantiomers of compounds 1 - 6 at muscarinic M] (r bit vas deferens), M2 (guinea-pig atria) and M3 receptors (guinea-pig ileum) center of chirality.

Cereda, E., Donetti, A., 1990. Affinity profile of the novel muscarinic antagonist, guanylpirenzepine. Life Sci. 47, PL55-PL58. 

The finding that the affinity profile of prazosin-related quinazolines can depend on the type of moiety linking the two nitrogen atoms of the piperazine ring of prazosin, prompted us to further modify the structure of analogue 2. In particular, two types of structural modifications were performed on the structure of 2, that is, replacement of the... 

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