Tissue selectivity

The possibility that 11-desoxyprostaglandins might exhibit tissue selectivity in therapeutic applications provided an incentive to develop a short synthetic route to this series (Ref. 1). 

Kenakin, T. P., and Beek, D. (1980). Is prenalterol (H 133/80) really a selective beta-1 adrenoceptor agonist Tissue selectivity resulting selective beta-1 adrenoceptor agonist Tissue selectivity resulting from difference in stimulus-response relationships. J. Pharmacol. Exp. Ther. 213 406—413. 

Molecnlar Mechanisms of SERM Action as a Means of Understanding their Tissue-Selective Activities... 

Wolters PJ, Mallen-St Clair J, Lewis CC, Villalta SA, 27 Baluk P, Erie DJ, Caughey GH Tissue-selective mast cell reconstitution and differential lung gene expression in mast cell-deficient sash mice. 

Kusuhara, H. and Y. Sugiyama. Role of transporters in the tissue-selective distribution and elimination of drugs transporters in the liver, small intestine, brain and kidney. J. Control. Release 2002, 78, 43-54. 

Yamazaki, M., Tokui, T., Ishigami, M., Sugiyama, Y., Tissue-selective uptake of pravastatin in rats contribution of a specific carrier-mediated uptake system, Biopharm. Drug Dispos. 1996, 17, 775-789. 

Ronkin S, Clarke L, Boudes P, Constantine G (2001) TSE-424, a novel tissue selective estrogen, reduces biochemical indices of bone metabolissm in a dose-related fashion. J Bone Miner Res 16(Suppl) S413... 

Fig. 3.2. Potential genomic and nongenomic activation routes thatmaybe induced by natural or synthetic ER ligands. The hypotheses that explain the tissue-selective action of SERMs include (a) selective activation of ER subtypes, (b) different changes in the 3D configuration of the ligand-ER complex, (c) recruitment of coactivator and corepressor proteins, and (d) activation of alternative response elements in certain inducible genes...

Evans GL, Turner NY (1995) Tissue selective actions of estrogens analogs. Bone 17(Suppl 4) 181S-190S... 

This is a third-generation SERM. It binds with high affinity to human estrogen receptors and acts as a tissue-selective estrogen antagonist or agonist. 

Grese TA, Sluka JP, Bryant HU, Culhnan GJ, Glasebrook AL, Jones CD, Matsumoto K, Palkowitz AD, Sato M, Termine JD, Winter MA, Yang NN, Dodge JA (1997) Molecular determinants of tissue selectivity in estrogen receptor modulators. Proc Natl Acad Sci USA 94(25) 14105—14110... 

Somjen D, Waisman A, Kaye AM (1996) Tissue selective action of tamoxifen methiodide, raloxifene and tamoxifen on creatine kinase B activity in vitro and in vivo. J Steroid Biochem Mol Biol 59(5-6) 389-396... 

Despite the discovery of ERcx selective SERMs and their subsequent use as chemical tools to evaluate the pharmacological significance of this receptor sub-type, the respective roles that ERcx and ER(3 play in regulating tissue selectivity is not yet clear. As a result, the identification of non-receptor subtype selective SERMs remains of considerable interest. Along these lines, isochroman 26 and... 

Tissue-selective activation of classical prodrugs Site-specific delivery of ad hoc chemical systems... 

Turning our attention first to alkyl carbamates of cyclic amides, we find interesting attempts to improve the pharmaceutical and pharmacokinetic properties of 5-fluorouracil (8.152, R = H) [194-196], This antitumor agent, while clinically useful, suffers from poor water solubility, unsatisfactory delivery properties and low tissue selectivity. A variety of prodrug candidates were prepared, in particular the alkyl and aryl carbamates presented in Table 8.12. With the exception of the more-lipophilic derivatives, these compounds exhibited somewhat improved water solubility. More importantly, both rectal and oral bioavailability were markedly improved. The activation... 

C. R. Sirtori, Tissue Selectivity of Hydroxymethylglutaryl Coenzyme A (HMG CoA) Reductase Inhibitors , Pharmacol. Ther. 1993, 60, 431-459. 

Voss, H.P., Shukrula, S., Wu, T.S., Donnell, D., and Bast, A., A functional beta-2 adrenoceptor-mediated chronotropic response in isolated guinea pig heart tissue selectivity of the potent beta-2 adrenoceptor agonist TA 2005, /. Pharmacol. Exp. Ther., 271, 386-389, 1994. 

De novo design generation of proteins Tissue selections... 

Table 14.2. Organ and tissue selective distribution of potential drug carriers based on receptor recognizing principles a few examples.

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