ARD-61

发表于由

上海金畔生物科技有限公司为生命科学和医药研发人员提供生物活性分子抑制剂、激动剂、特异性抑制剂、化合物库、重组蛋白，专注于信号通路和疾病研究领域。

ARD-61 

ARD-61 是一种高效、特异的 PROTAC 雄激素受体 (AR) 降解剂。ARD-61 有效且有效地诱导 AR+ 癌细胞系中的 AR 和孕酮受体 (PR) 降解。ARD-61 诱导细胞凋亡，也可有效抑制小鼠 MDA-MB-453 异种移植模型中的肿瘤生长。

ARD-61

ARD-61 Chemical Structure

CAS No. : 2316837-08-6

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生物活性

ARD-61 is a highly potent, effective and specific PROTAC androgen receptor (AR) degrader. ARD-61 potently and effectively induces AR and progesterone receptors (PR) degradation in AR+ cancer cell lines. ARD-61 induces apoptosis and effectively induces tumor growth inhibition in the MDA-MB-453 xenograft model in mice[1].

IC50 & Target[1]

VHL

 

体外研究
(In Vitro)

ARD-61 binds to AR protein through its AR antagonist portion and von Hippel-Lindau (VHL)/cullin 2 E3 ligase through its VHL ligand portion to recruit AR protein to cullin 2 for ubiquitination, followed by proteasome-dependent AR degradation[1].
ARD-61 (0.001-100 μM; for 7 days) has IC50 values of 235 nM and 121 nM in the MDA-MB-453 and HCC1428 cell lines, which have the highest AR expression, respectively. ARD-61 demonstrates partial cell growth inhibition, delivering IC50 values of 39, 147, and 380 nM, respectively, in the MCF-7, BT-549 and MDA-MB-415 cell lines, which have a moderate level of AR protein[1].
ARD-61 (25-100000 nM; 6-72 h) induces G2/M cell cycle arrest in a dose- and time-dependent manner in each of these three AR+ breast cancer cell lines[1].
ARD-61 (25-100000 nM; 72 h) induces apoptosis in the MDA-MB-453 and HCC1428 cell lines[1].
ARD-61 (0.01-1000 nM; 6 h) is highly potent and effective in reducing AR protein levels. ARD-61 (0.01-1000 nM; 24 h) reduces the level of PR protein with a DC50 value of 0.15 nM in the T47D cells. ARD-61 has no obvious effect on ER and GR proteins[1].
ARD-61 (1 µM; for 24 h) effectively inhibits Wnt/β-catenin and MYC signaling pathways. ARD-61 (1-1000 nM; for 24 h) not only decreases both phosphorylated HER2 and HER3, but also un-phosphorylated HER2 and HER3 proteins[1].
Efficient knock-down of VHL completely blocks AR degradation induced by ARD-61 (100 nM; 24 h) in both MDA-MB-453 and MCF-7 cell lines[1].

Shanghai Jinpan Biotech Co Ltd has not independently confirmed the accuracy of these methods. They are for reference only.

Cell Viability Assay[1]

Cell Line: MDA-MB-453 and HCC1428 cell lines
Concentration: 0.001, 0.01, 0.1, 1, 10, 100 μM
Incubation Time: 7 days
Result: Achieves near complete inhibition of cell growth.

Cell Cycle Analysis[1]

Cell Line: MDA-MB-453, HCC1428 and MCF-7 cell lines
Concentration: 25, 250, 500, 1000, 10000, 100000 nM
Incubation Time: 6-72 hours
Result: Induced G2/M cell cycle arrest in a dose- and time-dependent manner in each of these three AR+ breast cancer cell lines.

Apoptosis Analysis[1]

Cell Line: MDA-MB-453 and HCC1428 cell lines
Concentration: 25, 250, 500, 1000, 10000, 100000 nM
Incubation Time: 6-72 hours
Result: Induced apoptosis in the MDA-MB-453 and HCC1428 cell lines in a dose-dependent manner.

Western Blot Analysis[1]

Cell Line: MDA-MB-453, MCF-7, BT549, MDA-MB-415 and HCC1428 cell lines
Concentration: 0.01, 0.03, 0.1, 0.3, 1, 3, 10, 30, 100, 300, 1000 nM
Incubation Time: 6 hours
Result: Reduced AR protein levels in the MDA-MB-453 (DC50=0.44 nM), MCF-7 (DC50=1.8 nM), BT549 (DC50=2.0 nM), MDA-MB-415 (DC50=2.4 nM) and HCC1428 (DC50=3.0 nM) cell lines.

体内研究
(In Vivo)

ARD-61 (25, 50 mg/kg/day; ip; for 75 days) effectively inhibits tumor growthin the MDA-MB-453 xenograft tumor model in male SCID mice[1].
ARD-61 (25 mg/kg; ip; single dose) effectively and rapidly reduces the AR protein in the MDA-MB-453 xenograft tissue, with the effect persisting for at least 24 h. ARD-61 is very effective in reducing the mRNA level of WNT7B in a time-dependent manner[1].

Shanghai Jinpan Biotech Co Ltd has not independently confirmed the accuracy of these methods. They are for reference only.

Animal Model: MDA-MB-453 xenograft tumor model in male SCID mice[1]
Dosage: 25, 50 mg/kg
Administration: IP; daily; for 75 days
Result: Effectively inhibited tumor growth.

分子量

1095.78

Formula

C61H71ClN8O7S
CAS 号

2316837-08-6
运输条件

Room temperature in continental US; may vary elsewhere.
储存方式

Please store the product under the recommended conditions in the Certificate of Analysis.
参考文献

  • [1]. Lijie Zhao, et al. A highly potent PROTAC androgen receptor (AR) degrader ARD-61 effectively inhibits AR-positive breast cancer cell growth in vitro and tumor growth in vivo. Neoplasia. 2020 Oct;22(10):522-532.

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