4-Hydroxytamoxifen ≥70% Z isomer (remainder primarily E-isomer)

Cell permeable, synthetic estrogen receptor ligand. Active metabolite of tamoxifen. Widely used for inducible genome manipulation. ≥70% Z isomer (remainder primarily E-isomer).

Cre-LoxP / CreER system:

De facto standard for use in the inducible Cre-LoxP system for manipulation of CreER/CreERT2 recombinase for genome/ genetic manipulation (e.g. gene deletion). 4-OHT allows external temporal control of Cre activity in vivo.

TRAP / TRAP2

Used as part of the TRAP/TRAP2 systems (targeted recombination in active populations) (e.g. FosTRAP, ArcTRAP) to provide genetic access to neurons.

CRISPR/Cas9 gene editing:

Activates an inactived Cas9 nuclease (rendered inactive by insertion of a 4-OHT dependent-intein) to reduce off-target CRISPR-mediated gene editing (once bound with 4-OHT, conditionally active Cas9s modify target genomic sites with ~25-fold higher specificity than wild-type Cas9).

Also allows tight, repeated on-off control of the nuclease activity of the ‘iCas’ Cas9 variant which shows high editing efficiency at multiple loci once bound with 4-OHT.

Cancer:

Chemotherapeutic agent. Induces apoptosis through an ER-dependent mechanism and inhibits proliferation of multiple myeloma cells in vitro.

Pure (Z)-4-hydroxytamoxifen (100% isomer) also available.

Storage of solid

• This compound is light sensitive; exposure to light may affect compound performance. You should therefore store the material in the dark and protect from light.

Storage of solutions

• Do not store the material in solution; make up solutions and use immediately:
• The compound has been shown to isomerise rapidly in solution in most solvents (particularly solvents with a low dielectric constant). You should therefore make up and use solutions immediately.
• The isomerisation process can be precluded by storage of the compound at -25°C in the dark as a THF solution containing ca. 0.025% BHT. (Katzenellenbogen et al (1982) J. Org. Chem. 47 2387.)