Home>>Signaling Pathways>> PROTAC>>ARCC-4

ARCC-4 Sale

目录号 : GC60594

ARCC-4是基于PROTAC技术的,纳摩尔级的雄激素受体(AR)降解剂,其D50值为5 nM。ARCC-4是一种基于enzalutamide的vonHippel-Lindau(VHL)招募的ARPROTAC。ARCC-4能有效降解与抗雄激素研究相关的AR突变。

ARCC-4 Chemical Structure

Cas No.:1973403-00-7

规格 价格 库存 购买数量
5mg
¥3,420.00
现货
10mg
¥5,400.00
现货
25mg
¥10,350.00
现货

电话:400-920-5774 Email: sales@glpbio.cn

Customer Reviews

Based on customer reviews.

Sample solution is provided at 25 µL, 10mM.

产品文档

Quality Control & SDS

View current batch:

产品描述

ARCC-4 is a low-nanomolar androgen receptor (AR) degrader based on PROTAC, with a DC50 of 5 nM. ARCC-4 is an enzalutamide-based von Hippel-Lindau (VHL)-recruiting AR PROTAC and outperforms enzalutamide. ARCC-4 effectively degrades clinically relevant AR mutants associated with antiandrogen therapy[1].

ARCC-4 induces apoptosis and inhibiting proliferation of AR-amplified prostate cancer cells[1].ARCC-4 enhances protein-protein interactions between AR and VHL, thereby promoting the association of the trimeric complex[1].ARCC-4 (0.1-10,000 nM; 20 hours) potently degrades AR with a D50 of 5 nM and Dmax of over 95%[1].ARCC-4 (100 nM; 12 hours) shows near complete AR degradation (>98%) in prostate cancer cells[1]. ARCC-4 selectively degrades AR via the proteasome but not PR-A or PR-B suppression[1].ARCC-4 shows efficacy against clinically relevant AR mutations[1].ARCC-4 maintains activity despite elevated androgen levels[1]. Western Blot Analysis[1] Cell Line: VCaP cells

[1]. Salami J, et al. Androgen receptor degradation by the proteolysis-targeting chimera ARCC-4 outperforms enzalutamide in cellular models of prostate cancer drug resistance. Commun Biol. 2018 Aug 2;1:100.

Chemical Properties

Cas No. 1973403-00-7 SDF
Canonical SMILES O=C(NCC1=CC=C(C2=C(C)N=CS2)C=C1)[C@H]3N(C([C@H](C(C)(C)C)NC(COCCCCOC4=CC=C(C5=CC=C(N(C(N6C7=CC=C(C#N)C(C(F)(F)F)=C7)=S)C(C)(C)C6=O)C=C5)C=C4)=O)=O)C[C@H](O)C3
分子式 C53H56F3N7O7S2 分子量 1024.18
溶解度 DMSO: 200 mg/mL (195.28 mM); Water: < 0.1 mg/mL (insoluble) 储存条件 Store at -20°C
General tips 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 储存时,请在 6 个月内使用,-20°C 储存时,请在 1 个月内使用。
为了提高溶解度,请将管子加热至37℃,然后在超声波浴中震荡一段时间。
Shipping Condition 评估样品解决方案:配备蓝冰进行发货。所有其他可用尺寸:配备RT,或根据请求配备蓝冰。

溶解性数据

制备储备液
1 mg 5 mg 10 mg
1 mM 0.9764 mL 4.882 mL 9.7639 mL
5 mM 0.1953 mL 0.9764 mL 1.9528 mL
10 mM 0.0976 mL 0.4882 mL 0.9764 mL
  • 摩尔浓度计算器

  • 稀释计算器

  • 分子量计算器

质量
=
浓度
x
体积
x
分子量
 
 
 
*在配置溶液时,请务必参考产品标签上、MSDS / COA(可在Glpbio的产品页面获得)批次特异的分子量使用本工具。

计算

动物体内配方计算器 (澄清溶液)

第一步:请输入基本实验信息(考虑到实验过程中的损耗,建议多配一只动物的药量)
给药剂量 mg/kg 动物平均体重 g 每只动物给药体积 ul 动物数量
第二步:请输入动物体内配方组成(配方适用于不溶于水的药物;不同批次药物配方比例不同,请联系GLPBIO为您提供正确的澄清溶液配方)
% DMSO % % Tween 80 % saline
计算重置

Research Update

Androgen receptor degradation by the proteolysis-targeting chimera ARCC-4 outperforms enzalutamide in cellular models of prostate cancer drug resistance

Commun Biol 2018 Aug 2;1:100.PMID:30271980DOI:10.1038/s42003-018-0105-8.

The androgen receptor is a major driver of prostate cancer and inhibition of its transcriptional activity using competitive antagonists, such as enzalutamide remains a frontline therapy for prostate cancer management. However, the majority of patients eventually develop drug resistance. We propose that targeting the androgen receptor for degradation via Proteolysis Targeting Chimeras (PROTACs) will be a better therapeutic strategy for targeting androgen receptor signaling in prostate cancer cells. Here we perform a head-to-head comparison between a currently approved androgen receptor antagonist enzalutamide, and its PROTAC derivative, ARCC-4, across different cellular models of prostate cancer drug resistance. ARCC-4 is a low-nanomolar androgen receptor degrader able to degrade about 95% of cellular androgen receptors. ARCC-4 inhibits prostate tumor cell proliferation, degrades clinically relevant androgen receptor point mutants and unlike enzalutamide, retains antiproliferative effect in a high androgen environment. Thus, ARCC-4 exemplifies how protein degradation can address the drug resistance hurdles of enzalutamide.

Solubility Enhanced Formulation Approaches to Overcome Oral Delivery Obstacles of PROTACs

Pharmaceutics 2023 Jan 3;15(1):156.PMID:36678785DOI:10.3390/pharmaceutics15010156.

PROteolysis TArgeting Chimaeras (PROTACs) offer new opportunities in modern medicine by targeting proteins that are undruggable to classic inhibitors. However, due to their hydrophobic structure, PROTACs typically suffer from low solubility, and oral bioavailability remains challenging. At the same time, due to their investigative state, the drug supply is meager, leading to limited possibilities in terms of formulation development. Therefore, we investigated the solubility enhancement employing mini-scale formulations of amorphous solid dispersions (ASDs) and liquisolid formulations of the prototypic PROTAC ARCC-4. Based on preliminary supersaturation testing, HPMCAS (L Grade) and Eudragit® L 100-55 (EL 100-55) were demonstrated to be suitable polymers for supersaturation stabilization of ARCC-4. These two polymers were selected for preparing ASDs via vacuum compression molding (VCM), using drug loads of 10 and 20%, respectively. The ASDs were subsequently characterized with respect to their solid state via differential scanning calorimetry (DSC). Non-sink dissolution testing revealed that the physical mixtures (PMs) did not improve dissolution. At the same time, all ASDs enabled pronounced supersaturation of ARCC-4 without precipitation for the entire dissolution period. In contrast, liquisolid formulations failed in increasing ARCC-4 solubility. Hence, we demonstrated that ASD formation is a promising principle to overcome the low solubility of PROTACs.