UT-34

本公司产品仅用于科研实验，不得用于人体或动物的临床与诊断

UT-34 是第二代泛雄激素受体 (AR) 和降解剂的选择性口服活性拮抗剂（对于野生型、F876L 和 W741L AR，IC50 分别为 211.7 nM、262.4 nM 和 215.7 nM），并具有抗-前列腺癌功效。在 LNCaP 细胞中，UT-34（3-10 μM；24 小时）处理从 100 nM 开始抑制 PSA 和 FKBP5 的表达以及 LNCaP 细胞的生长，在 10 μM 时观察到最大效果。

UT-34 is a selective and orally active antagonist of second-generation pan-androgen receptor (AR) and degrader(IC50s of 211.7 nM, 262.4 nM and 215.7 nM for wild-type, F876L and W741L AR, respectively), and has anti-prostate cancer efficacy. In LNCaP cells, UT-34 (3-10 μM; 24 hours) treatment inhibits the expression of PSA and FKBP5 and growth of LNCaP cells starting from 100 nM with maximum effect observed at 10 μM.In LNCaP cells UT-34 (0.1-10 μM; 24 hours; LNCaP cells) treatment results in a reduction of AR levels at 1000 nM. 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. UT-34 is an effective degrader of both AR and AR-V7.LNCaP-ARV7 cells were treated in the presence of 0.1 nM R1881 or 10 ng/mL doxycycline for 24 hours. Doxycycline induces the expression of EDN2, which is inhibited by UT-34, and UT-34 inhibits the expression of FKBP5 gene expression induced by R1881.In NSG mice, UT-34 (20-40 mg/kg; oral administration; daily; for 14 days ) at 20 and 40 mg/kg reduces the seminal vesicle weight by 10%-20% and 50%-60 %, respectively[1]. in rats,UT-34 inhibits androgen-dependent tissues such as prostate and seminal vesicles , and the growth of Enzalutamide-resistant castration-resistant prostate cancer (CRPC) xenografts. In intact immunocompromised rats, UT-34 also induces tumor regression.

Cell Viability Assay 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 Cell Line:LNCaP cells Concentration:0.1 μM, 1 μM, 10 μM Incubation Time:24 hoursResult:Resulted in a reduction of AR levels at 1000 nM.

Animal Model:Non obese diabetic/severe combined immunodeficiency Gamma (NSG) mice injected with MR49F cells Dosage:20 mg/kg or 40 mg/kg Administration:Oral administration; daily; for 14 daysResult:Reduced the seminal vesicle weight.

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Endocrinology/Hormones

Androgen Receptor (AR)

androgen receptor

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2168525-92-4

356.27

C15H12F4N4O2

>98% (HPLC)

DMSO:71 mg/mL (199.29 mM)

C[C@](O)(Cn1cc(F)cn1)C(=O)Nc1ccc(C#N)c(c1)C(F)(F)F

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(-20℃)

With Ice Pack

≥ 2 years