(Z)-Endoxifen

July 21, 2026: Atossa Therapeutics, Inc. (NASDAQ: ATOS) announced presentation of a preclinical poster at the AACR Special Conference in Cancer Research: Breaking Barriers in the Fight Against Rare Cancers (July 18–20, 2026; poster session July 18) describing a proposed dual mechanism for (Z)-endoxifen in McCune-Albright Syndrome–associated peripheral precocious puberty (MAS-PPP). The poster (Abstract A010; presenter Sandra Hammer, PhD) reports that (Z)-endoxifen may both block estrogen receptor (ER)-mediated transcription downstream of autonomous estrogen production and suppress PKC-β/AKT-associated proliferative and cell-cycle signaling.

Using weighted gene expression signatures in ER-positive MCF7 cells and integrating published phosphoproteomic and RNA-seq datasets, the analysis identified an estrogen-responsive gene network and found (Z)-endoxifen downregulated cell-cycle programs (including G2M Checkpoint and E2F Targets) while modulating estrogen-response pathways. Integrated mechanistic data also indicated (Z)-endoxifen targets PKC-β1, promoting dephosphorylation/degradation and inhibiting PMA-induced PKC-β1 and AKT phosphorylation. The company said the findings support further evaluation of (Z)-endoxifen for MAS-PPP and may be relevant to estrogen-driven neoplasms.