(Z)-4-hydroxy Tamoxifen 是一种口服具有活力的雌激素受体选择性调节剂 (SERM)。它基于 ER 介导的细胞核易位诱导 CRISPR/Cas9 系统。

4-Hydroxytamoxifen is a selective estrogen receptor modulator (SERM).

4-Hydroxytamoxifen can inhibit the [3H]estradiol binding to the estrogen receptor (IC50: 3.3 nM). 4-Hydroxytamoxifen (10/100 nM) has an inhibition for the binding of [3H]oestradiol to the human 8 S estrogen receptor[1]. 4-Hydroxytamoxifen activates intein-linked inactive Cas9, decreases off-target CRISPR-mediated gene editing. In human cells, the specificity modification of target genomic sites of conditionally active Cas9s is higher 25-fold than wild-type Cas9[2].

4-Hydroxytamoxifen (0.2/1/5 μg/day, p.o.) dose-dependently decreases the uterine wet weight of immature rats[1]. In C57BL/6 J mice, 4-Hydroxytamoxifen (6 μg/0.1 mL sesame oil/day, s.c.) potently attenuates methamphetamine-induced nigrostriatal dopamine depletion in both sexes of intact and gonadectomized. 4-Hydroxytamoxifen has no effect on the dopamine content levels in the striatum[3].

Cytosol (200 μL) is incubated for 30 min at 4°C with different concentrations of oestradiol, tamoxifen and (4-Hydroxytamoxifen) or dihydroxytamoxifen administered in 10 μL methanol. Control tubes are incubated with 10 μL methanol alone and non-specific binding is determined in a parallel incubation of cytosol (200 μL) with methanol (10 μL) containing DES (5 × 106 M). [2,4,6,7-3H]Oestradiol solution (50 μL) in TED buffer is added to each tube to give a final concentration of 2 × 10-9 M. Incubation is continued for 4 h (4°C) and then 400 μL of a suspension of dextran-coated charcoal (250 mg % Norit A, 2.5 mg % dextran) in TED buffer is added and allowed to stand for 20 min. Tubes are centrifuged at 800 g for 10 min (4°C) and 400 μL samples of the supernatant are added to 10 mL tritium scintillator (6 g butyl PBD, 135 mL toluene, 720 ml dioxane, 100 g naphthalene, 45 mL absolute methanol). Samples are counted for 10 min in a liquid scintillation spectrometer. Counting efficiency is determined by external standardization (35-36 %). Results are represented as a percentage of the specifically bound radioactivity (c.p.m.) in the control tubes[1].

4-Hydroxytamoxifen is formulated in sesame oil[3].Animals of each sex are divided into two groups: one group receives 4-Hydroxytamoxifen [6 μg/0.1 mL sesame oil/day, subcutaneously (s.c.) starting at 06.00 h] injections for three consecutive days, while the other group receives an equivalent amount of sesame oil injection for 3 days. Four hours following the third injection, each group is then subdivided into two groups: one receives four cumulative doses of methamphetamine hydrochloride (10 mg/kg, s.c.), and the other receives a comparable volume of saline at 2-h intervals. Bilateral gonadectomy is performed under pentobarbital anesthesia (50 mg/kg, intraperitoneally). Five weeks after surgery, gonadectomized mice of each sex are randomly divided into six groups. Five groups of each sex receive three daily injections of various concentrations of 4-Hydroxytamoxifen (0, 1.5, 3.0, 6.0, and 12.0 μg/0.1 mL sesame oil/day). Four hours following the third injection, mice receive four doses of methamphetamine (MA, 10 mg/kg) at 2-h intervals. The remaining group of each sex receives sesame oil pretreatment for three consecutive days, followed by saline injections, and serves as the control group[3].

68047-06-3

C26H29NO2

387.523

trans-4-Hydroxytamoxifen;(Z)-4-hydroxy Tamoxifen;ICI 79280;4-羟基他莫昔芬

H2O:< 0.1 mg/mL (insoluble)
DMSO:28 mg/mL (72.26 mM)
Powder: -20°C for 3 years
In solvent: -80°C for 2 years