ESR1 and neoplasm: In the case of (Z)-4-hydroxytamoxifen (4-OHT), which is the active metaboliteof tamoxifen, H12 is repositioned, AF2 is not formed, and interactionswith coactivator peptides are blocked in hormone-dependent tumor cells,preventing their growth.11,12 Nevertheless, in someother target tissues (endometrium, bones), activation is possibledue to an insufficient shielding of the charge at Asp351 (at ERα)by the basic side chain.