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Biological Activity:

(Z)-4-Hydroxytamoxifen (also called 4-OH-TAM) was previously characterized as an Estrogen Receptor antagonist and now found to improve genome-editing specificity in CRISPR-mediated gene editing. It can activate intein-linked inactive Cas9, reducing off-target. Such system has ~25-fold higher specificity than wtCas9. (Z)-4-Hydroxytamoxifen is a Tamoxifen metabolite to be used as chemotherapeutic agent. It exhibits greater potency than Tamoxifen.

How to Use:

In vitro: (Z)-4-Hydroxytamoxifen was used at 1 µM final concentration in CRISPR-mediated gene editing experiments.
In vivo: (Z)-4-Hydroxytamoxifen was used at 10 mg/Kg orally for the in vivo animal models.

Reference:

• 1. Jordan VC, et al. A monohydroxylated metabolite of tamoxifen with potent antioestrogenic activity. (1977) J Endocrinol. 75(2):305-16.
• 2. Desta Z, et al. Comprehensive evalsuation of tamoxifen sequential biotransformation by the human cytochrome P450 system in vitro: prominent roles for CYP3A and CYP2D6. (2004) J Pharmacol Exp Ther. 310(3):1062-75.
• 3. Davis KM, et al. Small molecule-triggered Cas9 protein with improved genome-editing specificity (2015) Nat Chem Biol. 11(5):316-8.