AGN194204 is an Orally Active and Selective RXR Agonist
Posted On 2020-03-03
Rexinoids are selective ligands for the retinoid X receptors (RXRα, RXRβ, and RXRγ). Specifically, rexinoids are multifunctional drugs that are useful for both the prevention and treatment of lung and breast cancer in preclinical animal models. Besides, retinoid X receptors heterodimerize with other receptors in the nuclear receptor superfamily. They modulate the activities of numerous steroid-like molecules and thus regulate cell proliferation, differentiation, and apoptosis pathways. Moreover, Retinoids are small-molecule hormones that exert their biological effects by activating nuclear receptors and modulating gene transcription. Furthermore, Retinoids play key roles in both embryogenesis and maintenance of various cellular processes such as cell growth and differentiation. The ability of RXRs to form heterodimers with other receptors has established a central role for these proteins in many endocrine signaling pathways. AGN194204 is an orally active and selective RXR agonist with anti-inflammatory and anticarcinogenic actions.
AGN194204 (IRX4204) is an orally active and selective RXR agonist with Kd values 0.4 nM, 3.6 nM and 3.8 nM for RXRα, RXRβ and RXRγ, respectively. Meanwhile, AGN194204 has EC50s of 0.2 nM, 0.8 nM and 0.08 nM for RXRα, RXRβ and RXRγ, respectively. Nonetheless, AGN194204 is inactive against RAR and has anti-inflammatory and anticarcinogenic actions. In the A/J mouse model of lung cancer, AGN194204 significantly reduced the number and size of tumors on the surface of the lungs. Finally, AGN194204 reduced the total tumor volume per slide by 64% to 81%. All in all, AGN194204 is an orally active and selective RXR agonist with anti-inflammatory and anticarcinogenic actions.
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