ARD-2128 is a highly potent, orally bioavailable PROTAC androgen receptor (AR) degrader. ARD-2128 effectively reduces AR protein, suppresses AR-regulated genes in tumor tissues, and inhibits growth of tumor without signs of toxicity. ARD-2128 has the potential for the research of the prostate cancer^[1].

IC50: 4 nM (VCaP), 5 μM (LNCaP)^[1]

ARD-2128 is highly potent and effective in the inhibition of cell growth in the VCaP cell line and LNCaP cell line with the IC₅₀ values of 4 nM and 5 nM, respectively^[1].
ARD-2128 (1, 10, 100, and 1000 nM; 24 hours) effectively reduces the AR protein level by >50% at 1 nM and achieves the AR degradation of >90% at 10, 100, and 1000 nM, respectively, in VCaP cell^[1].

上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.

ARD-2128 (20 mg/kg; p.o.; once) is effective in reducing the level of AR protein in mice after 24 hours^[1].
ARD-2128 (10-40 mg/kg; p.o.; daily for 21 days) shows antitumor activity in the VCaP xenograft model in mice^[1].
ARD-2128 (5mg/kg; p.o.) treatment shows the C_max, AUC_0-t and t_1/2 values of 1304 ng/mL, 22361 ng h/mL and 18.8 hours, respectively^[1].

上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.

820.37

C₄₅H₅₀ClN₇O₆

2222111-87-5

Room temperature in continental US; may vary elsewhere.

DMSO : 100 mg/mL (121.90 mM; Need ultrasonic)

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°C, 6 months; -20°C, 1 month。-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。

• [1]. Han X, et al. Strategies toward Discovery of Potent and Orally Bioavailable Proteolysis Targeting Chimera Degraders of Androgen Receptor for the Treatment of Prostate Cancer [published online ahead of print, 2021 Aug 25]. J Med Chem. 2021;10.1021/acs.jmedchem.1c00882.

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].

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.

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.

1095.78

C₆₁H₇₁ClN₈O₇S

2316837-08-6

Room temperature in continental US; may vary elsewhere.

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

• [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.

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].

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.

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.

1095.78

C₆₁H₇₁ClN₈O₇S

2316837-08-6

Room temperature in continental US; may vary elsewhere.

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

• [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.

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].

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].

上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.

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].

上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.

1095.78

C₆₁H₇₁ClN₈O₇S

2316837-08-6

Room temperature in continental US; may vary elsewhere.

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

• [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.

ARD-266 is a highly potent and von Hippel-Lindau E3 ligase-based Androgen Receptor (AR) PROTAC degrader. ARD-266 effectively induces degradation of AR protein in AR-positive LNCaP, VCaP, and 22Rv1 prostate cancer cell lines with DC₅₀ values of 0.2-1 nM^[1].

ARD-266 (Compound 11; 100 nM; 1-24 hours; LNCaP and VCaP cells) treatment effectively reduces the AR protein level within 3 h and achieves near-complete AR elimination with a 6 h treatment in the LNCaP cells^[1].
ARD-266 (Compound 11; 1-10000 nM; 24 hours; LNCaP cells) treatment effectively suppresses the expression of PSA, TMPRSS2, and FKBP5 genes in a dosedependent manner and is capable of reducing the mRNA levels of PSA, TMPRSS2, and FKBP5 genes by >50% at 10 nM in the LNCaP cell line^[1].

上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.

915.51

C₅₂H₅₉ClN₆O₇

Room temperature in continental US; may vary elsewhere.

DMSO : 100 mg/mL (109.23 mM; Need ultrasonic)

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°C, 6 months; -20°C, 1 month。-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。

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: 5 mg/mL (5.46 mM); Suspended solution; Need ultrasonic

  此方案可获得 5 mg/mL (5.46 mM) 的均匀悬浊液，悬浊液可用于口服和腹腔注射。

  以 1 mL 工作液为例，取 100 μL 50.0 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。

  将 0.9 g 氯化钠，完全溶解于 100 mL ddH₂O 中，得到澄清透明的生理盐水溶液

• 2.

  请依序添加每种溶剂： 10% DMSO    90% (20% SBE-β-CD in saline)

  Solubility: 5 mg/mL (5.46 mM); Suspended solution; Need ultrasonic

  此方案可获得 5 mg/mL (5.46 mM) 的均匀悬浊液，悬浊液可用于口服和腹腔注射。

  以 1 mL 工作液为例，取 100 μL 50.0 mg/mL 的澄清 DMSO 储备液加到 900 μL 20% 的 SBE-β-CD 生理盐水水溶液中，混合均匀。

  将 2 g 磺丁基醚 β-环糊精加入 5 mL 生理盐水中，再用生理盐水定容至 10 mL，完全溶解，澄清透明
• 3.

  请依序添加每种溶剂： 10% DMSO    90% corn oil

  Solubility: ≥ 5 mg/mL (5.46 mM); Clear solution

  此方案可获得 ≥ 5 mg/mL (5.46 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 50.0 mg/mL 的澄清 DMSO 储备液加到 900 μL玉米油中，混合均匀。

• [1]. Han X, et al. Discovery of Highly Potent and Efficient PROTAC Degraders of Androgen Receptor (AR) by Employing Weak Binding Affinity VHL E3 Ligase Ligands. J Med Chem. 2019 Dec 26;62(24):11218-11231.