Retinoid antagonist

Proton Pump Inhibitors and Acid Pump Antagonists retinoid X receptor (RXR) and is also activated by various lipophilic compounds produced by the body such as bile acids and steroids. PXR heterodimerized with RXR stimulates the transcription of cytochrome P450 3A monooxygenases (CYP3A) and other genes involved in the detoxification and elimination of the... 

Benzimidazole and benzodiazepines derivatives as retinoid antagonists 96YZ928. 

The antagonist-induced conformation of nuclear hormone receptors attracts co-repressors like Nco/SMRT (nuclear hormone receptor co-repressor/silencing mediator of retinoid and thyroid receptors) which further recruit other nuclear proteins with histone deacetylase activity. Their action leads to chromatin condensation, thus preventing the general transcription apparatus from binding to promoter regions. 

Synthetic Retinoid Receptor Selective Agonists/ Antagonists... 

It has been shown that the expression of connexin 43 (Cx43) is upregulated by cancer-preventive retinoids and carotenoids, which correlate with the suppression of carcinogen-induced transformation in 10T1/2 cells. Recently, it has been reported that Cx43 induction by astaxanthin, but not by a RAR-specific retinoid, was inhibited by GW9662, a PPARy antagonist (Bertram et al., 2005). 

Agarwal C, Chandraratna RA, Johnson AT, Rorke EA, and Eckert RL [1996] AGN193109 is a highly effective antagonist of retinoid action in human ectocervical epithelial cells. J Biol Chem 271 12209-12212... 

Dr David Graham from the FDA, speaking to the US senate in 2004, controversially raised concerns (refuted by the respective Pharmaceutical Companies) over the safety of the retinoid, isotretinoin (used in the treatment of cancer), the statin, rosuvastatin (used to lower cholesterol), a long-acting p2-receptor antagonist, salmeterol (used in asthma therapy), and a selective serotonin reuptake inhibitor, paroxetine (used as an antidepressant) (21). 

Toxicologically the function of the terminal hormones of endocrine cascades (i.e., steroid, retinoid, thyroid hormones) appear to be most susceptible to disruption by chemicals. This is because many foreign molecules share sufficient characteristics with these hormone molecules to allow binding to the nuclear receptors of these hormones in either an agonistic or antagonistic fashion. The binding of the xenobiotic to the... 

The present and future efforts of medicinal chemists in the development of novel retinoid compounds are discussed in this section. This body of work should ultimately lead to receptor and receptor subtype-selective agonists and antagonists and novel compounds that block proliferative signaling processes. 

Adapalene (6) is a naphthoic acid derivative with a methoxyphenyl adamant side-chain and is a commonly used antiacne drug [74]. Similar to the adion of tazarotene in its hydrolyzed form, tazarotenic acid, adapalene interacts seledively with RARP and RARy, and its activity on proliferation and differentiation can be blocked by a RARy antagonist [75]. In addition, adapalene has antiinflammatory potential due to its anti-API adivity [75]. Although its efficacy is similar to that of other retinoids, it has an improved therapeutic ratio due to its better tolerance (reviewed in Ref. [76]). 

Eyrolles, L., Kagechika, H., Kawachi, E., Fukasawa, H., Iijima, T., Matsushima, Y., Hashimoto, Y. and Shudo, K. (1994) Retinobenzoic adds. 6. Retinoid antagonists with a heterocydic ring. Journal of Medicinal Chemistry, 37, 1508-1517. 

Lumsden, 2001 Wendling et al., 2001). Blocking retinoid signaling therefore results in a caudal truncation of the hindbrain, with hindbrain disruptions being progressively more severe the earlier the treatment. In the most extreme form of retinoid deprivation elicited by antagonist treatments, the caudal hindbrain becomes truncated below r4, while the remaining rhombomeres are expanded. 

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