Abstract: Disclosed are methods and compositions relating to modulators, such as agonists and antagonists, of HNF4?.

Abstract: Disclosed are methods and compositions relating to antagonists of HNF4?.

Abstract: Bridged bicyclic aromatic compounds are provided having the structure ##STR1## wherein R.sup.1, R.sup.2, R.sup.3, R.sup.4, R.sup.5 and n are as defined herein. The novel compounds are useful for modulating gene expression of retinoic acid receptors, vitamin D receptors and thyroid receptors. Pharmaceutical compositions and methods for modulating gene expression are provided as well.

Abstract: The invention provides a method of screening a substance for the ability to effect the formation of a retinoid X receptor homodimer comprising combining the substance and a solution containing retinoid X receptors and determining the presence of homodimer formation. Also provided is a method of screening a substance for an effect on a retinoid X receptor homodimer's ability to bind DNA comprising combining the substance with the homodimer and determining the effect of the compound on the homodimer's ability to bind DNA. A method of inhibiting an activity of a retinoid X receptor heterodimer comprising increasing the formation of a retinoid X receptor homodimer, thereby preventing the retinoid X receptor from forming a heterodimer and preventing the resulting heterodimer activity is also provided. A method of inhibiting an activity of a retinoid X receptor homodimer is also provided.

Abstract: The invention provides a method of screening a substance for the ability to effect the formation of a retinoid X receptor homodimer comprising combining the substance and a solution containing retinoid X receptors and determining the presence of homodimer formation. Also provided is a method of screening a substance for an effect on a retinoid X receptor homodimer's ability to bind DNA comprising combining the substance with the homodimer and determining the effect of the compound on the homodimer's ability to bind DNA. A method of inhibiting an activity of a retinoid X receptor heterodimer comprising increasing the formation of a retinoid X receptor homodimer, thereby preventing the retinoid X receptor from forming a heterodimer and preventing the resulting heterodimer activity is also provided. A method of inhibiting an activity of a retinoid X receptor homodimer is also provided. In addition, a method of screening a response element for binding with a retinoid X receptor homodimer is provided.

Abstract: Aromatic retinoic acid analogues of the formula ##STR1## where X is hydrogen or fluorine, Y is hydrogen, halogen of atomic number 9 or 17, hydroxy, alkyl of 1 to 2 carbon atoms or alkoxy of 1 to 2 carbon atoms and R is hydroxy, alkoxy, aroxy, or NR.sup.1 R.sup.2 where R.sup.1 is hydrogen, alkyl, or aryl and R.sup.2 is alkyl or aryl, with the proviso that when Y is hydrogen, X is fluorine. These retinoids are useful as chemopreventive agents for inhibiting tumor promotion in epithelial cells and for treating nonmalignant skin disorders.

Abstract: Retinoic acid-4,4,18,18,18-d.sub.5 and esters and amides thereof are disclosed. These compounds are useful as chemopreventive agents for inhibiting tumor promotion in epithelial cells and for treating nonmalignant skin disorders.

Abstract: A compound of the formula: ##STR1## where X is ##STR2## and R is hydroxy, or an alkoxy with 0 or 1 hydroxy substituent, or aroxy with 0 or 1 hydroxy substituent, or alkoxy monosubstituted phenoxy, or NR.sup.1 R.sup.2 where R.sup.1 is hydrogen, or an alkyl or aryl with 0 or 1 hydroxy substituent, and R.sup.2 is an alkyl or aryl with 0 or 1 hydroxy substituent. These compounds are useful as chemopreventive agents for inhibiting tumor promotion in ephithelial cells and for treating nonmalignant skin disorders.

Abstract: Naphthenic and heterocyclic retinoic acid analogues such as (E)-6-[2-(2,6,6-trimethyl-1-cyclohexen-1-yl)ethenyl]-2-naphthaldehyde, methyl 6-[2-(2,6,6-trimethyl-1-cyclohexen-1-yl)ethenyl]-2-naphthoate, 6-[2-(2,6,6-trimethyl-1-cyclohexen-1-yl)ethenyl]-2-naphthoic acid, (E)-1-(5-carbethoxy-2-furanyl)-2-methyl-4-(2,6,6-trimethyl-1-cyclohexen-1- yl)-1,3-butadiene, (E)-1-(5-carboxy-2-furanyl)-2-methyl-4-(2,6,6-trimethyl-1-cyclohexen-1-yl) -1,3-butadiene, (E)-1-(5-carbethoxythien-2-yl)-2-methyl-4-(2,6,6-trimethyl-1-cyclohexen-1- yl)-1,3-butadiene, and (E)-1-(5-carboxythien-2-yl)-2-methyl-4-(2,6,6-trimethyl-1-cyclohexen-1-yl) -1,3-butadiene. These retinoids are useful as chemopreventive agents for inhibiting tumor promotion in epithelial cells and for treating nonmalignant skin disorders.

Abstract: Open ring retinoic acid analogues and 2Z isomers of the formula ##STR1## where X is ##STR2## and R is hydroxy, alkoxy with 0 or 1 hydroxy substituent, aroxy with 0 or 1 hydroxy or alkoxy-monosubstituted phenoxy or NR.sup.1 R.sup.2 where R.sup.1 is hydrogen, alkyl, or aryl and R.sup.2 is alkyl or aryl are disclosed. These retinoids are useful as chemopreventive agents for inhibiting tumor promotion in epithelial cells and for treating nonmalignant skin disorders.

Abstract: Pentaerythritol retinoates and monobenzal acetals thereof such as (E)-2.sub..alpha. -phenyl-5.sub..alpha. -hydroxy-methyl-5.sub..beta. -retinoyloxymethyl-1,3-dioxane, (E)-2.sub..alpha. -phenyl-5.sub..beta. -hydroxymethyl-5.sub..alpha. -retinoyloxymethyl-1,3-dioxane, and pentaerythritol monoretinoate are disclosed. These retinoids are useful as chemopreventive agents and as therapeutic agents for treating nonmalignant skin disorders.

Abstract: Naphthenic and heterocyclic retinoic acid analogues such as (E)-6-[2-(2,6,6-trimethyl-1-cyclohexen-1-yl)ethenyl]-2-naphthaldehyde, methyl 6-[2-(2,6,6-trimethyl-1-cyclohexen-1-yl)ethenyl]-2-naphthoate, 6-[2-(2,6,6-trimethyl-1-cyclohexen-1-yl)ethenyl]-2-naphthoic acid, (E)-1-(5-carbethoxy-2-furanyl)-2-methyl-4-(2,6,6-trimethyl-1-cyclohexen-1- yl)-1,3-butadiene, (E)-1-(5-carboxy-2-furanyl)-2-methyl-4-(2,6,6-trimethyl-1-cyclohexen-1-yl) -1,3-butadiene, (E)-1-(5-carbethoxythien-2-yl)-2-methyl-4-(2,6,6-trimethyl-1-cyclohexen-1- yl)-1,3-butadiene, and (E)-1-(5-carboxythien-2-yl)-2-methyl-4-(2,6,6-trimethyl-1-cyclohexen-1-yl) -1,3-butadiene. These retinoids are useful as chemopreventive agents for inhibiting tumor promotion in epithelial cells and for treating nonmalignant skin disorders.

Abstract: Compounds of the formulas: ##STR1## where X is methyl, methoxy, chlorine, or hydrogen, Y and Y.sub.1 are fluorine or hydrogen, R is hydroxy, alkoxy with 0 or 1 hydroxy substituent, aroxy, or NR.sup.1 R.sup.2 where R.sup.1 is hydrogen, alkyl with 0 or 1 hydroxy substituent or aryl and R.sup.2 is alkyl with 0 or 1 hydroxy substituent or aryl with the proviso that when Y or Y.sup.1 is fluorine, the other Y or Y.sup.1 is hydrogen. These compounds are useful as chemopreventive agents for inhibiting tumor promotion in epithelial cells and for treating nonmalignant skin disorders.

Abstract: 5,6-Methano-5,6-dihydroretinoids such as ethyl (E)-5,6-methano-5,6-dihydroretinoate and (E)-1-(4-carbethoxyphenyl)-2-methyl-4-(2,2,6-trimethylbicyclo[4.1.0]hept-1 -yl)-1,3-butadiene are disclosed. These componds are useful as chemopreventive agents for inhibiting tumor promotion in epithelial cells and for treating nonmalignant skin disorders.