Retinoid, RARy selective

Roy, B., Taneja, R., and Chambon, P. (1995). Synergistic activation of retinoic acid (RA)-re-sponsive genes and induction of embryonal carcinoma ceU differentiation by an RA receptor a (RARa)-, RARP-, or RARy-selective ligand in combination vdth a retinoid X receptor-specific ligand. Mol. Cell. Biol. 15, 6481-6487. 

Figure 1. Concentration-dependent transcriptional activation of the retinoic acid receptor subtypes a, p, and yon the (TREpal)2-tfc-CAT reporter construct in CV-1 cells by (A) RARa-selective retinoids Am580 (RARa, RARp, RARy A) and Am80 (RARa, O RARp, RARy A), and (B) RARy-selective retinoids SRI 1254 (RARa, RARP, RARy A) and AHPN (RARa, O RARp, RARy A).

Because the skin contains RARa and RARy proteins, with the latter predominating (1 6) [12], research is devoted to establishing the predominant signalling pathway in the skin in order to develop more effective dermatological agents [127]. Yu et al. [59] reported that RARa-selective retinoids had greater potency than RARy-selective retinoids at reducing utricule size in... 

To further complicate this biological-activity scheme, as well as the central importance observed for RARa and RARP in mediating RA activity in breast cancer, recent studies have demonstrated the relevance of the third member of the RAR family, RARy. This receptor also seems to play a role in controlling the growth of breast cancer cells [36], being elevated by RA treatment in several ER and ER" cells, concomitant of retinoid responsiveness [37]. These data are also confirmed by the retained biological activity of RARy-selective retinoids in comparison with RA, as observed by successive studies [38]. 

In Table 3 are listed the structures and transcriptional activation activities of retinoids reported as receptor-selective based on their preferential ability to induce one retinoid receptor complex to activate gene transcription from a particular RE compared to the activities of the standards. These retinoid agonists are commonly used to identify the retinoid receptor having the most influence on a particular retinoid-signalling pathway. Four retinoids—TTNPB [23], TTNN [51], TTAB [53, 54], SRI 1256 [104], and SRI 1365 [105]—are listed as RAR class selective because they only activate the RARs. Of these, TTNPB, TTAB, and the A-oxide SRI 1365 are the most transcriptionally selective across all RAR subtypes, whereas TTNN preferentially activates RAR(3 and RARy. At higher concentrations SRI 1256,4-[3-(5,6,7,8-tetrahy-dro-5,5,8,8-tetramethyl-2-naphthalenyl)phenyl]benzoic acid, can also activate the RXRs. The parent 4-(6,7,8,9-tetrahydro-6,6,9,9-tetramethylnaphtho[2,3-Z ]pyridin-2-yl)benzoic acid from which SRI 1365 is derived was first reported by the Shudo group [106]. 

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