In vitro: ASC-J9 is able to degrade fAR and AR3 in a dose-dependent manner in various human PCa cells. ASC-J9 can also effectively suppress AR-targeted genes in CWR22Rv1-fARKD cells. ASC-J9 (5 or 10 µM) significantly suppresses the DHT-induced cell growth in all three PCa cell lines. ASC-J9 suppresses AR-targeted genes and cell growth by degradation of fAR and ectopic AR3 in C81 and C4-2 cells. ASC-J9 selectively promotes AR degradation by disrupting the interaction between AR and AR coregulators. ASC-J9 reduces the AR aggregated AR-112Q in cells.
In vivo: ASC-J9 (75 mg/kg, i.p.) degrades both fAR and AR3 in the xenografted tumors in vivo, and SC-J9-treated tumors has significantly decreased Ki67-positive cells. ASC-J9 (50 mg/kg every 48 h, i.p.) substantially ameliorates the SBMA symptoms in AR-97Q mice, and ameliorates neuromuscular pathological findings. The ASC-J9-treated SBMA mice have relatively normal serum testosterone concentrations. ASC-J9-treated mice show significantly smaller prostate tumor sizes when compared with those receiving classic ADT/castration with little serum androgen.
|Cell lines||PC12/AR-112Q and PC12/AR-10Q cells|
|Preparation method||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 vehicle, 5 μM ASC-J9 or 10 μM ASC-J9, along with 1 nM DHT, and determined cell viability using Trypan blue staining at specific time intervals.|
|Animal models||both anterior prostates of castrated nude mouse|
|Body Surface Area (m2)||0.007||0.025||0.15||0.05||0.02||0.5|
|Animal A (mg/kg) = Animal B (mg/kg) multiplied by||Animal B Km|
|Animal A Km|
For example, to modify the dose of resveratrol used for a mouse (22.4 mg/kg) to a dose based on the BSA for a rat, multiply 22.4 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for resveratrol of 11.2 mg/kg.
Targeting androgen receptor with ASC-J9 attenuates cardiac injury and dysfunction in experimental autoimmune myocarditis by reducing M1-like macrophage.
Ma W, et al. Biochem Biophys Res Commun. 2017 Apr 15;485(4):746-752. PMID: 28246012.
ASC-J9 suppresses castration-resistant prostate cancer growth through degradation of full-length and splice variant androgen receptors.
Yamashita S, et al. Neoplasia. 2012 Jan;14(1):74-83. PMID: 22355276.
ASC-J9 ameliorates spinal and bulbar muscular atrophy phenotype via degradation of androgen receptor.
Yang Z, et al. Nat Med. 2007 Mar;13(3):348-53. PMID: 17334372.
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