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 Experiment | |
|---|---|
| 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. |
| Concentrations | |
| Incubation time | |
| Animal Experiment | |
|---|---|
| Animal models | both anterior prostates of castrated nude mouse |
| Formulation | |
| Dosages | 75 mg/kg |
| Administration | intraperitoneal injection |
| Molecular Weight | 396.43 |
| Formula | C23H24O6 |
| CAS Number | 52328-98-0 |
| Solubility (25°C) | DMSO |
| Storage |
Powder -20°C 3 years ; 4°C 2 years In solvent -80°C 6 months ; -20°C 1 month |
| Species | Mouse | Rat | Rabbit | Guinea pig | Hamster | Dog |
| Weight (kg) | 0.02 | 0.15 | 1.8 | 0.4 | 0.08 | 10 |
| Body Surface Area (m2) | 0.007 | 0.025 | 0.15 | 0.05 | 0.02 | 0.5 |
| Km factor | 3 | 6 | 12 | 8 | 5 | 20 |
| Animal A (mg/kg) = Animal B (mg/kg) multiplied by | Animal B Km |
| Animal A Km |
For example, to modify the dose of Compound A used for a mouse (20 mg/kg) to a dose based on the BSA for a rat, multiply 20 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 Compound A of 10 mg/kg.
| Related Androgen Receptor Products |
|---|
| BMS-986365
BMS-986365 (CC-94676) is a selective heterobifunctional ligand-directed degrader (LDD) with a dual mechanism-of-action and best-in-class potential, targeting the androgen receptor (AR). In animal models of advanced prostate cancer, BMS-986365 demonstrates on-target activity, degrading AR, suppressing AR signaling, and inhibiting tumor growth. |
| Androstenone
Androstenone is a steroid pheromone and also a metabolite of androgens. |
| (Des-Glu5)-ACTH (1-24) (human, bovine, rat)
(Des-Glu5)-ACTH (1-24) (human, bovine, rat) is an analogue of Adrenocorticotropic hormone (ACTH). |
| Acetyl-ACTH (2-24) (human, bovine, rat)
Acetyl-ACTH (2-24) (human, bovine, rat) is a fragment of proopiomelanocortin (POMC) peptide. |
| Acetyl-ACTH (3-24) (human, bovine, rat)
Acetyl-ACTH (3-24) (human, bovine, rat) is a fragment of proopiomelanocortin (POMC) peptide. |
Products are for research use only. Not for human use. We do not sell to patients.
© Copyright 2010-2023 AbMole BioScience. All Rights Reserved.
