Background:

Target: RARγ, RARβ and RARα

Ki: 150, 1500, and 2750 nM

CD1530 is a potent and selective RAR receptor agonist with Ki values of 150, 1500 and 2750 nM for RARγ, RARβ and RARα receptors, respectively [1]. In addition, CD1530 shows moderate RARγ selectivity in the transcriptional assay with AC50 value of 1.8 nM. RAR-α is present in the majority of tissues while the distribution of RAR-β and γ is more selective [1]. RARγ mediated retinoic acid (RA)-induced growth arrest and apoptosis of neoplastic mouse papilloma cell lines [2].

In vitro: CD1530 inhibited excessive ROS production in tongue epithelial cells [2]. In addition, CD1530 was also a potent CYP26A1 inhibitor as ketoconazole with an IC50 value of 530 nM [3].

In vivo: The combination of the drugs bexarotene (300 mg/kg) and CD1530 (2.5 mg/100 mL in drinking water) was more effective than either drug alone in preventing oral carcinogenesis induced by the carcinogen 4-nitroquinoline 1-oxide (4-NQO) in a mouse model of oral-cavity squamous-cell carcinoma (OCSCC), which did not cause cardiovascular risks [2]. High fat diet (HFD)-fed mice treated with CD1530 (2.5 mg/100 ml in drinking water) showed no decreases in steatosis, Kupffer cell TGF-β1 expression, or Hepatic stellate cells (HSCs) activation [4].

参考文献:
1.  Thacher SM, Vasudevan J, Chandraratna RA. Therapeutic applications for ligands of retinoid receptors. Curr Pharm Des. 2000;6(1):25-58.
2.  Tang XH, Osei-Sarfo K, Urvalek AM, Zhang T, Scognamiglio T, Gudas LJ. Combination of bexarotene and the retinoid CD1530 reduces murine oral-cavity carcinogenesis induced by the carcinogen 4-nitroquinoline 1-oxide. Proc Natl Acad Sci U S A. 2014;111(24):8907-12.
3.  Thatcher JE, Buttrick B, Shaffer SA, Shimshoni JA, Goodlett DR, Nelson WL, et al. Substrate specificity and ligand interactions of CYP26A1, the human liver retinoic acid hydroxylase. Mol Pharmacol. 2011;80(2):228-39.
4.  Trasino SE, Tang XH, Jessurun J, Gudas LJ. A retinoic acid receptor beta2 agonist reduces hepatic stellate cell activation in nonalcoholic fatty liver disease. J Mol Med (Berl). 2016.