XS-060 is a potent anticancer agent and RXRα antagonist. XS-060 significantly induces RXRα-dependent mitotic arrest by inhibiting pRXRα-PLK1 interaction. XS-060 inhibits p-RXRα interaction with PLK1 but has no effect on RXRα heterodimerization with RARγ. XS-060 inhibits the in situ interaction between p-RXRα and PLK1 at the centrosome.
XS-060 targeting the RXRα′ s coactivator binding site can inhibit pRXRα-PLK1 interaction and exhibits good antitumor activity as an anti-mitotic agent[1].XS-060 shows anti-proliferative activity against MDA-MB 231 cancer cells, with an IC50 of 6.880 ± 0.059 μM[1].
XS-060 (25 mg/kg, IP or PO, once) displays good absorption by intraperitoneal injection, but oral absorption is very poor[1].
References:
[1]. Chen J, et al. Discovery of bipyridine amide derivatives targeting pRXRα-PLK1 interaction for anticancer therapy. Eur J Med Chem. 2023 Apr 6;254:115341.
[2]. Xie G, et al. Centrosomal Localization of RXRα Promotes PLK1 Activation and Mitotic Progression and Constitutes a Tumor Vulnerability. Dev Cell. 2020 Dec 21;55(6):707-722.e9.