CIDD-0169124

CIDD-0169124 is a next-generation, brain-penetrant small molecule agonist of the estrogen receptor beta (ERβ). Developed by researchers at the University of Texas at San Antonio (UTSA) and UT Health San Antonio, it is an indanone- or tetralone-keto/hydroxyloxime derivative optimized from the earlier lead compound CIDD-0149897. CIDD-0169124 exhibits high selectivity for ERβ over ERα and superior blood-brain barrier permeability, achieving a peak brain-to-plasma ratio of approximately 3.12. In preclinical studies, the compound has demonstrated the ability to reduce the viability of glioblastoma stem cells (GSCs) and significantly enhance the therapeutic response to temozolomide (TMZ) by increasing DNA damage and suppressing neurosphere formation. In orthotopic xenograft models of glioblastoma, CIDD-0169124 has been shown to reduce tumor burden and prolong survival, both as a monotherapy and in combination with TMZ.