| Description | Dimethylcurcumin (ASC-J9) (ASC-J9) is an androgen receptor degradation enhancer. It effectively suppresses castration-resistant prostate cancer cell proliferation and invasion. |
| In vitro | Dimethylcurcumin 在不同的人类前列腺癌细胞中以剂量依赖的方式降解 fAR 和 AR3。在 CWR22Rv1-fARKD 细胞中，Dimethylcurcumin 也能有效地抑制 AR 靶基因。Dimethylcurcumin (5 或 10 μM) 显著抑制三种前列腺癌细胞线中 DHT 诱导的细胞增长。Dimethylcurcumin 通过降解 C81 和 C4-2 细胞中的 fAR 和异位 AR3 来抑制 AR 靶基因和细胞生长 [1]。ASC-J9 减少细胞中 AR 聚集的 AR-112Q。Dimethylcurcumin 抑制 SBMA PC12/AR-112Q 细胞中的 AR-112Q 聚集 [2]。 |
| In vivo | Dimethylcurcumin（75 mg/kg，腹腔注射）能在体内降解异种移植肿瘤中的fAR和AR3，并且经ASC-J9处理的肿瘤显示Ki67阳性细胞显著减少[1]。Dimethylcurcumin（50 mg/kg，每48小时一次，腹腔注射）显著改善了AR-97Q小鼠的脊髓性肌萎缩症状，并改善了神经肌肉病理学发现[2]。与接受经典ADT/去势治疗且血清雄激素水平较低的小鼠相比，ASC-J9处理的小鼠展示了显著更小的前列腺肿瘤体积[3]。 |
| Cell experiments | For the cell survival assay, the PC12/AR-112Q and PC12/AR-10Q cells are cultured as described previously and incubated cells in the presence of 10 μg/mL doxycycline for 24 h. Then the cells are treated with a vehicle, 5 μM Dimethylcurcumin or 10 μM Dimethylcurcumin, along with 1 nM DHT, and determined cell viability using Trypan blue staining at specific time intervals [2]. |
| Animal experiments | CWR22Rv1 cells (1×10^6 cells per site) are injected into both anterior prostates of the castrated nude mice after 2 weeks of implantation. The mice were randomly divided into two groups (four mice/eight tumors each group) and either receive 75 mg/kg Dimethylcurcumin intraperitoneal injection or vehicle control every other day. After 4 weeks of treatment, all mice are killed to examine the tumor growth. Body weights and mice activity are measured weekly [1]. |
| Synonyms | ASC-J9, 二甲基姜黄素, GO-Y025 |
| molecular weight | 396.43 |
| Molecular formula | C23H24O6 |
| CAS | 52328-98-0 |
| Storage | Powder: -20°C for 3 years | In solvent: -80°C for 1 year |
| Solubility | DMSO: 48 mg/mL (121.08 mM) H2O: Insoluble |
| References | 1. Yamashita S, et al. ASC-J9 suppresses castration-resistant prostate cancer growth through degradation of full-length and splice variant androgen receptors. Neoplasia. 2012 Jan;14(1):74-83. 2. Yang Z, et al. ASC-J9 ameliorates spinal and bulbar muscular atrophy phenotype via degradation of androgen receptor. Nat Med. 2007 Mar;13(3):348-53. 3. Lee SO, et al. New therapy targeting differential androgen receptor signaling in prostate cancer stem/progenitor vs non-stem/progenitor cells. J Mol Cell Biol. 2012 Jul 24. 4. Ma W, et al. Targeting androgen receptor with ASC-J9 attenuates cardiac injury and dysfunction in experimental autoimmune myocarditis by reducing M1-like macrophage. Biochem Biophys Res Commun. 2017 Apr 15;485(4):746-752. doi: 10.1016/j.bbrc.2017.02.123. Epub 2017 Feb 27. |