Retinoid, RARy subtype-selective

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).

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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