4OHT

4OHT, short for 4-hydroxytamoxifen, is the active metabolite of the selective estrogen receptor modulator tamoxifen and a high-affinity ligand for estrogen receptors ERα and ERβ. In research, 4OHT is widely used to induce Cre recombinase activity in Cre-ERT2 (or CreER) inducible systems, enabling temporal control of genetic modification.

In cells expressing a CreER fusion protein, CreER is retained in the cytoplasm in the absence of ligand. Binding of 4OHT promotes a conformational change that releases CreER, allowing it to translocate to the nucleus and catalyze recombination at loxP sites. This enables inducible knockout, activation, or lineage tracing of target genes.

Chemically, 4OHT is the active metabolite of tamoxifen and acts as a potent estrogen receptor ligand. It often provides faster and more consistent induction than tamoxifen because it does not require metabolic activation to engage CreER. It binds ERα and ERβ, with tissue- and context-dependent estrogenic or antiestrogenic effects.

Applications and handling: In vitro studies typically use low micromolar to sub-micromolar concentrations; in vivo use requires established dosing regimens in mouse or other models. 4OHT is prepared as a stock solution in organic solvents such as ethanol or DMSO and diluted in culture medium or administered to animals under standard laboratory safety guidelines.

Safety: 4OHT is a hormonal modulator and not approved for clinical use. It should be handled in accordance with institutional safety procedures, with attention to potential estrogenic effects and off-target actions in experimental systems.