UT-34 是一种有效的,选择性的,具有口服活性的第二代泛雄激素受体 (AR) 拮抗剂和降解剂,对野生型AR,F876L-AR和W741L-AR的IC50分别为 211.7 nM,262.4 nM 和 215.7 nM。UT-34 与配体结合结构域 (LBD) 和功能 1 (AF-1) 结构域结合,并需要泛素蛋白酶体途径来降解AR。UT-34 具有抗前列腺癌的功效。
生物活性 | UT-34 is a potent, selective and orally active second-generation pan-androgen receptor(AR)antagonist and degrader withIC50s of 211.7 nM, 262.4 nM and 215.7 nM forwild-type,F876LandW741L AR, respectively. UT-34 binds to ligand-binding domain (LBD) and function-1 (AF-1) domains and requires ubiquitinproteasomepathway to degrade theAR. UT-34 has anti-prostatecancerefficacy[1][2]. |
IC50& Target | IC50: 211.7 nM (Wild-type AR), 262.4 nM (F876L AR) and 215.7 nM (W741L AR)[1] |
体外研究 (In Vitro) | UT-34 (3-10 μM; 24 hours; LNCaP cells) treatment inhibits the expression of PSA and FKBP5 and growth of LNCaP cells starting from 100 nM with maximum effect observed at 10 μM[1]. UT-34 (0.1-10 μM; 24 hours; LNCaP cells) treatment results in a reduction of AR levels at 1000 nM in LNCaP cells[1]. Treatment of ZR-75-1 cells maintained in serum-containing growth medium with UT-34 results in downregulation of AR protein levels, but not estrogen receptor (ER) or progesterone receptor (PR) levels. Furthermore, in MDA-MB-453 breast cancer cells that express AR and glucocorticoid receptor (GR), UT-34 induces the downregulation of AR, but not GR[1]. UT-34 is an effective degrader of both AR and AR-V7. LNCaP-ARV7 cells are treated for 24 hours in the presence of 0.1 nM R1881 or 10 ng/mL Doxycycline. Doxycycline induces the expression of EDN2, which is inhibited by UT-34, while UT-34 inhibits the expression of R1881-induced FKBP5 gene expression[1].
Cell Viability Assay[1] Cell Line: | LNCaP cells | Concentration: | 3 μM, 10 μM | Incubation Time: | 24 hours | Result: | Inhibited the expression of PSA and FKBP5 and growth of LNCaP cells starting from 100 nM with maximum effect observed at 10 μM. |
Western Blot Analysis[1] Cell Line: | LNCaP cells | Concentration: | 0.1 μM, 1 μM, 10 μM | Incubation Time: | 24 hours | Result: | Resulted in a reduction of AR levels at 1000 nM. |
|
体内研究 (In Vivo) | UT-34 (20-40 mg/kg; oral administration; daily; for 14 days; NSG mice) at 20 and 40 mg/kg reduces the seminal vesicle weight by 10%-20% and 50%-60 %, respectively[1]. UT-34 inhibits androgen-dependent tissues such as prostate and seminal vesicles in rats, and the growth of Enzalutamide-resistant castration-resistant prostate cancer (CRPC) xenografts. UT-34 also induces tumor regression in intact immunocompromised rats[1].
Animal Model: | Non obese diabetic/severe combined immunodeficiency Gamma (NSG) mice injected with MR49F cells[1] | Dosage: | 20 mg/kg or 40 mg/kg | Administration: | Oral administration; daily; for 14 days | Result: | Reduced the seminal vesicle weight. |
|
分子量 | |
性状 | |
Formula | |
CAS 号 | |
运输条件 | Room temperature in continental US; may vary elsewhere. |
储存方式 | Powder | -20°C | 3 years | | 4°C | 2 years | In solvent | -80°C | 6 months | | -20°C | 1 month |
|
溶解性数据 | In Vitro: DMSO : 250 mg/mL(701.71 mM;Need ultrasonic) 配制储备液 1 mM | 2.8069 mL | 14.0343 mL | 28.0686 mL | 5 mM | 0.5614 mL | 2.8069 mL | 5.6137 mL | 10 mM | 0.2807 mL | 1.4034 mL | 2.8069 mL |
*请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液;一旦配成溶液,请分装保存,避免反复冻融造成的产品失效。 储备液的保存方式和期限:-80℃, 6 months; -20℃, 1 month。-80℃ 储存时,请在 6 个月内使用,-20℃ 储存时,请在 1 个月内使用。 In Vivo: 请根据您的实验动物和给药方式选择适当的溶解方案。以下溶解方案都请先按照In Vitro方式配制澄清的储备液,再依次添加助溶剂: ——为保证实验结果的可靠性,澄清的储备液可以根据储存条件,适当保存;体内实验的工作液,建议您现用现配,当天使用;
以下溶剂前显示的百 分比是指该溶剂在您配制终溶液中的体积占比;如在配制过程中出现沉淀、析出现象,可以通过加热和/或超声的方式助溶 1. 请依序添加每种溶剂: 10% DMSO 40%PEG300 5%Tween-80 45% saline Solubility: ≥ 2.08 mg/mL (5.84 mM); Clear solution
此方案可获得 ≥ 2.08 mg/mL (5.84 mM,饱和度未知) 的澄清溶液。 以 1 mL 工作液为例,取 100 μL 20.8 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中,混合均匀;向上述体系中加入50 μL Tween-80,混合均匀;然后继续加入 450 μL生理盐水定容至 1 mL。 2. 请依序添加每种溶剂: 10% DMSO 90% (20%SBE-β-CDin saline) Solubility: ≥ 2.08 mg/mL (5.84 mM); Clear solution
此方案可获得 ≥ 2.08 mg/mL (5.84 mM,饱和度未知) 的澄清溶液。 以 1 mL 工作液为例,取 100 μL 20.8 mg/mL 的澄清 DMSO 储备液加到 900 μL20% 的 SBE-β-CD 生理盐水水溶液中,混合均匀。 3. 请依序添加每种溶剂: 10% DMSO 90%corn oil Solubility: ≥ 2.08 mg/mL (5.84 mM); Clear solution
此方案可获得 ≥ 2.08 mg/mL (5.84 mM,饱和度未知) 的澄清溶液,此方案不适用于实验周期在半个月以上的实验。 以 1 mL 工作液为例,取 100 μL 20.8 mg/mL 的澄清 DMSO 储备液加到 900 μL玉米油中,混合均匀。 *以上所有助溶剂都可在本网站选购。
|