product name ARN-509
Description: ARN-509, also known as Apalutamide and JNJ-56021927, is a selective and competitive androgen receptor inhibitor with IC50 of 16 nM in a cell-free assay, it is useful for the treatment of prostate cancer. ARN-509 binds to AR in target tissues thereby preventing androgen-induced receptor activation and facilitating the formation of inactive complexes that cannot be translocated to the nucleus.
References: Cancer Res. 2012 Mar 15;72(6):1494-503; J Biol Chem. 1999 Jun 4;274(23):16147-52.
477.43
Formula
C21H15F4N5O2S
CAS No.
956104-40-8
Storage
-20℃ for 3 years in powder form
-80℃ for 2 years in solvent
Solubility (In vitro)
DMSO: 18 mg/mL (37.7 mM)
Water: <1 mg/mL
Ethanol: 5 mg/mL (10.5 mM)
Solubility (In vivo)
0.5% CMC, pH4.0: 14 mg/mL
Synonyms
other peoduct :References PubMed ID：:http://www.ncbi.nlm.nih.gov/pubmed/19394652
| In Vitro |
In vitro activity: ARN-509 (< 10 μM) inhibits androgen-mediated induction or repression of mRNA expression levels for 13 endogenous genes including PSA and TMPRSS2 in the LNCaP/AR prostate cancer cell line. ARN-509 (< 10 μM) inhibits the proliferative effect of R1881 (30 pM) in the LNCaP/AR prostate cancer cell line. ARN-509 (10 μM) impairs AR nuclear localization and thus reduces the concentration of AR available to bind androgen response elements (ARE) in LNCaP cells expressing AR-EYFP. ARN-509 (10 μM) is able to effectively compete with R1881 (1 nM) and prevent AR from binding to promoter regions. ARN-509 inhibits R1881-induced VP16-AR–mediated transcription with IC50 of 0.2 μM in Hep-G2 cells expressing a VP16-AR fusion protein and an ARE-driven luciferase reporter. Kinase Assay: Cell Assay: Cells are incubated for 48 hours, after which ARN-509 is added in a 16 μL volume to the RPMI culture medium. For the antagonist mode assay, the ARN-509 is diluted in culture medium also containing 30 pM R1881. After 7 days incubation, 16 μL of CellTiter-Glo Luminescent Cell Viability Assay is added and Relative Luminescence Units (RLUs) measured. |
|---|---|
| In Vivo | ARN-509 (10 mg/kg/d, oral) inhibits tumor growth with decreased proliferative index and increased apoptotic rate in castrate male immunodeficient mice harboring LNCaP/AR-luc xenograft tumors. ARN-509 dose dependently inhibits tumor growth with highest efficacy at dose of 30 mg/kg/day in castrate male immunodeficient mice harboring LNCaP/AR-luc xenograft tumors. ARN-509 dosed at 10 mg/kg/d for 28 days results in a 3-fold reduction in prostates weight associated with lacking glandular secretory activity and 1.7-fold reduction in epididymis weight in adult male dogs. ARN-509 (10 mg/kg/d, oral) inhibits cell proliferation of prostate tissues in adult male dogs. ARN-509 is safe and well tolerated in 24 patients with metastatic CRPC who has progressed on prior treatments and peak plasma concentrations occurred 2 to 3 hours after administration. ARN-509 results in durable PSA declines at doses ranging from 30 to 300 mg in patients with metastatic CRPC. ARN-509 shows powerful anti-cancer activity and induces durable remissions long after therapy completion in castrate resistant prostate cancer mouse models. |
| Animal model | Castrate male immunodeficient mice harboring LNCaP/AR-luc xenograft tumors |
| Formulation & Dosage | Dissolved in 15% Vitamin E-TPGS and 65% of a 0.5% w/v CMC solution in 20 mM citrate buffer (pH 4.0), and diluted in saline; 30 mg/kg/day; oral administration |
| References | Cancer Res. 2012 Mar 15;72(6):1494-503; J Biol Chem. 1999 Jun 4;274(23):16147-52. |
Related Posts
product name ARN-509
Description: ARN-509, also known as Apalutamide and JNJ-56021927, is a selective and competitive androgen receptor inhibitor with IC50 of 16 nM in a cell-free assay, it is useful for the treatment of prostate cancer. ARN-509 binds to AR in target tissues thereby preventing androgen-induced receptor activation and facilitating the formation of inactive complexes that cannot be translocated to the nucleus.
References: Cancer Res. 2012 Mar 15;72(6):1494-503; J Biol Chem. 1999 Jun 4;274(23):16147-52.
477.43
Formula
C21H15F4N5O2S
CAS No.
956104-40-8
Storage
-20℃ for 3 years in powder form
-80℃ for 2 years in solvent
Solubility (In vitro)
DMSO: 18 mg/mL (37.7 mM)
Water: <1 mg/mL
Ethanol: 5 mg/mL (10.5 mM)
Solubility (In vivo)
0.5% CMC, pH4.0: 14 mg/mL
Synonyms
other peoduct :References PubMed ID：:http://www.ncbi.nlm.nih.gov/pubmed/19394652
| In Vitro |
In vitro activity: ARN-509 (< 10 μM) inhibits androgen-mediated induction or repression of mRNA expression levels for 13 endogenous genes including PSA and TMPRSS2 in the LNCaP/AR prostate cancer cell line. ARN-509 (< 10 μM) inhibits the proliferative effect of R1881 (30 pM) in the LNCaP/AR prostate cancer cell line. ARN-509 (10 μM) impairs AR nuclear localization and thus reduces the concentration of AR available to bind androgen response elements (ARE) in LNCaP cells expressing AR-EYFP. ARN-509 (10 μM) is able to effectively compete with R1881 (1 nM) and prevent AR from binding to promoter regions. ARN-509 inhibits R1881-induced VP16-AR–mediated transcription with IC50 of 0.2 μM in Hep-G2 cells expressing a VP16-AR fusion protein and an ARE-driven luciferase reporter. Kinase Assay: Cell Assay: Cells are incubated for 48 hours, after which ARN-509 is added in a 16 μL volume to the RPMI culture medium. For the antagonist mode assay, the ARN-509 is diluted in culture medium also containing 30 pM R1881. After 7 days incubation, 16 μL of CellTiter-Glo Luminescent Cell Viability Assay is added and Relative Luminescence Units (RLUs) measured. |
|---|---|
| In Vivo | ARN-509 (10 mg/kg/d, oral) inhibits tumor growth with decreased proliferative index and increased apoptotic rate in castrate male immunodeficient mice harboring LNCaP/AR-luc xenograft tumors. ARN-509 dose dependently inhibits tumor growth with highest efficacy at dose of 30 mg/kg/day in castrate male immunodeficient mice harboring LNCaP/AR-luc xenograft tumors. ARN-509 dosed at 10 mg/kg/d for 28 days results in a 3-fold reduction in prostates weight associated with lacking glandular secretory activity and 1.7-fold reduction in epididymis weight in adult male dogs. ARN-509 (10 mg/kg/d, oral) inhibits cell proliferation of prostate tissues in adult male dogs. ARN-509 is safe and well tolerated in 24 patients with metastatic CRPC who has progressed on prior treatments and peak plasma concentrations occurred 2 to 3 hours after administration. ARN-509 results in durable PSA declines at doses ranging from 30 to 300 mg in patients with metastatic CRPC. ARN-509 shows powerful anti-cancer activity and induces durable remissions long after therapy completion in castrate resistant prostate cancer mouse models. |
| Animal model | Castrate male immunodeficient mice harboring LNCaP/AR-luc xenograft tumors |
| Formulation & Dosage | Dissolved in 15% Vitamin E-TPGS and 65% of a 0.5% w/v CMC solution in 20 mM citrate buffer (pH 4.0), and diluted in saline; 30 mg/kg/day; oral administration |
| References | Cancer Res. 2012 Mar 15;72(6):1494-503; J Biol Chem. 1999 Jun 4;274(23):16147-52. |