Home Endocrinology & Hormones Androgen Receptor antagonist ARN-509 (Apalutamide)

solo para uso en investigación

ARN-509 (Apalutamide) AR Antagonist

Cat. No.: S2840

Apalutamide (ARN-509) is a selective and competitive androgen receptor inhibitor with IC50 of 16 nM in a cell-free assay, useful for prostate cancer treatment. Phase 3.
ARN-509 (Apalutamide) Androgen Receptor antagonist Chemical Structure

Estructura química

Peso molecular: 477.43

Saltar a

Control de calidad (Quality Control)

Lote: Pureza: 99.98%
99.98

Cultivo celular, tratamiento y concentración de trabajo
(Cell Culture, Treatment & Working Concentration)

Líneas celulares Tipo de ensayo Concentración Tiempo de incubación Formulación Descripción de la actividad PMID
LNCAP cells Proliferation assay 3 days Antiproliferative activity against human LNCAP cells after 3 days, IC50=0.174 μM 26046313
PSN1 cells Cytotoxicity assay 96 h Cytotoxicity against human PSN1 cells after 96 hrs by ATP-lite luminescence assay, IC50=0.06 μM 22247788
PSN1 cells Function assay 30 nM 24 h Induction of cell cycle arrest in human PSN1 cells assessed as accumulation at G2/M phase cells at 30 nM after 24 hrs by flow cytometry 22247788
LNCaP Function assay 30 mins Displacement of [3H]-R1881 from AR in human LNCaP cells preincubated for 30 mins followed by [3H]-R1881 addition measured after 30 mins by microbeta scintillation counter method, IC50 = 0.01625 μM. 28478926
U-2 OS qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for U-2 OS cells 29435139
A673 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for A673 cells 29435139
DAOY qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for DAOY cells 29435139
BT-37 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for BT-37 cells 29435139
RD qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for RD cells 29435139
SK-N-SH qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for SK-N-SH cells 29435139
BT-12 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for BT-12 cells 29435139
MG 63 (6-TG R) qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for MG 63 (6-TG R) cells 29435139
NB1643 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for NB1643 cells 29435139
Fibroblast cells qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for control Hh wild type fibroblast cells 29435139
Rh41 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Rh41 cells 29435139
Rh30 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Rh30 cells 29435139
SJ-GBM2 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for SJ-GBM2 cells 29435139
SK-N-MC qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for SK-N-MC cells 29435139
NB-EBc1 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for NB-EBc1 cells 29435139
LAN-5 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for LAN-5 cells 29435139
Rh18 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Rh18 cells 29435139
Haga clic para ver más datos experimentales de líneas celulares

Información química, almacenamiento y estabilidad (Chemical Information, Storage & Stability)

Peso molecular 477.43 Fórmula

C21H15F4N5O2S

 Almacenamiento (Desde la fecha de recepción)
Nº CAS 956104-40-8 Descargar SDF Almacenamiento de soluciones madre

Sinónimos N/A Smiles CNC(=O)C1=C(C=C(C=C1)N2C(=S)N(C(=O)C23CCC3)C4=CC(=C(N=C4)C#N)C(F)(F)F)F

Solubilidad (Solubility)

In vitro
Lote:

DMSO : 95 mg/mL (198.98 mM)
(El DMSO contaminado con humedad puede reducir la solubilidad. Usar DMSO fresco y anhidro.)

Ethanol : 7 mg/mL

Water : Insoluble

Calculadora de Molaridad

Masa Concentración Volumen Peso molecular
Calculadora de Dilución Calculadora de Peso Molecular

In vivo
Lote:

Calculadora de formulación in vivo (Solución clara)

Paso 1: Introduzca la información a continuación (Recomendado: Un animal adicional para tener en cuenta la pérdida durante el experimento)

mg/kg g μL

Paso 2: Introduzca la formulación in vivo (Esto es solo la calculadora, no la formulación. Por favor, contáctenos primero si no hay una formulación in vivo en la sección de Solubilidad.)

% DMSO % % Tween 80 % ddH2O
%DMSO %

Resultados del cálculo:

Concentración de trabajo: mg/ml;

Método para preparar el líquido maestro de DMSO: mg fármaco predissuelto en μL DMSO ( Concentración del líquido maestro mg/mL, Por favor, contáctenos primero si la concentración excede la solubilidad del DMSO del lote del fármaco. )

Método para preparar la formulación in vivo: Tomar μL DMSO líquido maestro, luego añadirμL PEG300, mezclar y clarificar, luego añadirμL Tween 80, mezclar y clarificar, luego añadir μL ddH2O, mezclar y clarificar.

Método para preparar la formulación in vivo: Tomar μL DMSO líquido maestro, luego añadir μL Aceite de maíz, mezclar y clarificar.

Nota: 1. Por favor, asegúrese de que el líquido esté claro antes de añadir el siguiente disolvente.
2. Asegúrese de añadir el (los) disolvente(s) en orden. Debe asegurarse de que la solución obtenida, en la adición anterior, sea una solución clara antes de proceder a añadir el siguiente disolvente. Se pueden utilizar métodos físicos como el vórtice, el ultrasonido o el baño de agua caliente para ayudar a la disolución.

Mecanismo de acción (Mechanism of Action)

Targets/IC50/Ki
Androgen Receptor
(Cell-free assay)
16 nM
In vitro

Apalutamide (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. It also inhibits the proliferative effect of R1881 (30 pM) in the same cell line. At 10 μM, this compound impairs AR nuclear localization and thus reduces the concentration of AR available to bind androgen response elements (ARE) in LNCaP cells expressing AR-EYFP. It is able to effectively compete with R1881 (1 nM) and prevent AR from binding to promoter regions. Additionally, it 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.

In vivo

Apalutamide (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. This compound 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. It 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. The compound (10 mg/kg/d, oral) inhibits cell proliferation of prostate tissues in adult male dogs. It 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. This agent results in durable PSA declines at doses ranging from 30 to 300 mg in patients with metastatic CRPC. It shows powerful anti-cancer activity and induces durable remissions long after therapy completion in castrate resistant prostate cancer mouse models.

Referencias
  • [1] https://pubmed.ncbi.nlm.nih.gov/22266222/
  • [2] http://www.asco.org/ASCOv2/Meetings/Abstracts?&vmview=abst_detail_view&confID=116&abstractID=89154
  • [3] http://www.pcf.org/atf/cf/%7B7C77D6A2-5859-4D60-AF47-132FD0F85892%7D/PCFStateScience2010.pdf