Home PI3K/Akt/mTOR PI3K inhibitor Copanlisib (BAY 80-6946)

solo para uso en investigación

Copanlisib (BAY 80-6946) PI3K inhibitor

Cat. No.: S2802

Copanlisib is a potent pan-class I PI3K with IC50 of 0.5, 3.7, 6.4, and 0.7 nM in cell-free assays for PI3Kα/β/γ/δ , respectively. Phase 3.This product has poor solubility, animal experiments are available, cell experiments please choose carefully!
Copanlisib (BAY 80-6946) PI3K inhibitor Chemical Structure

Estructura química

Peso molecular: 480.52

Saltar a

Control de calidad (Quality Control)

Lote: Pureza: 99.74%
99.74

Productos que se suelen utilizar junto con Copanlisib (BAY 80-6946)

Anetumab ravtansine

The combination of this compound and Anetumab ravtansine shows an increase in apoptosis in the OVCAR-3 and OVCAR-8 cell lines.

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
Huh7 Growth inhibiton assay 100 nM Copanlisib dose-dependently inhibited cell growth in vitro. IC50=47.9 nM. 30962952
HepG2 Growth inhibiton assay 100 nM Copanlisib dose-dependently inhibited cell growth in vitro. IC50=31.6 nM. 30962952
Hep3B Growth inhibiton assay IC50=72.4 nM 30962952
PLCPRF5 Growth inhibiton assay IC50=283 nM 30962952
Chang Growth inhibiton assay IC50=442 nM 30962952
JVM-3 Function assay 48 h inhibits metabolic activity with an IC50 of 2 μM in the XTT assay 25912635
BT-474 Function assay 50 nM 0.5, 2, 4, 8, 24 h rapidly inhibits the phosphorylation of AKT (S473, T308) as well as its direct substrates PRAS40 (T246) and GSK3β (S9), and inhibition was sustained for up to 24 hours 24436048
SK-BR-3 Function assay 0, 1, 2, 4 h downregulation of P-AKT 24436048
UACC-893 Function assay 0, 1, 2, 4 h downregulation of P-AKT 24436048
HCC-1954 Function assay 0, 1, 2, 4 h downregulation of P-AKT 24436048
MDA-MB-453 Function assay 0, 1, 2, 4 h downregulation of P-AKT 24436048
MDA-MB-361 Function assay 0, 1, 2, 4 h downregulation of P-AKT 24436048
BT-20 Function assay 0, 1, 2, 4 h downregulation of P-AKT 24436048
MCF-7 Function assay 0, 1, 2, 4 h downregulation of P-AKT 24436048
T-47D Function assay 0, 1, 2, 4 h downregulation of P-AKT 24436048
HCC1806 Function assay 0, 1, 2, 4 h downregulation of P-AKT 24436048
NCI-H292 Function assay 0, 1, 2, 4 h downregulation of P-AKT 24436048
NCI-H1650 Function assay 0, 1, 2, 4 h downregulation of P-AKT 24436048
CCRF-SB Function assay 0, 1, 2, 4 h downregulation of P-AKT 24436048
U937 Function assay 0, 1, 2, 4 h downregulation of P-AKT 24436048
SU-DHL-4 Function assay 0, 1, 2, 4 h downregulation of P-AKT 24436048
SU-DHL-5 Function assay 0, 1, 2, 4 h downregulation of P-AKT 24436048
HCT116 Function assay 0, 1, 2, 4 h downregulation of P-AKT 24436048
A549 cells Function assay 0, 1, 2, 4 h downregulation of P-AKT 24436048
SK-MEL-30 Function assay 0, 1, 2, 4 h downregulation of P-AKT 24436048
SK-MEL-2 cells Function assay 0, 1, 2, 4 h downregulation of P-AKT 24436048
NCI-H1703 Function assay 0, 1, 2, 4 h downregulation of P-AKT 24436048
NCI-H661 Function assay 0, 1, 2, 4 h downregulation of P-AKT 24436048
PC9 Function assay 0, 1, 2, 4 h downregulation of P-AKT 24436048
TC32 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for TC32 cells 29435139
A673 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for A673 cells 29435139
Saos-2 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Saos-2 cells 29435139
RD qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for RD 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
OHS-50 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for OHS-50 cells 29435139
LAN-5 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for LAN-5 cells 29435139
NB-EBc1 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for NB-EBc1 cells 29435139
SK-N-SH qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for SK-N-SH cells 29435139
Rh41 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Rh41 cells 29435139
A673 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for A673 cells) 29435139
BT-37 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for BT-37 cells 29435139
MG 63 (6-TG R) qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for MG 63 (6-TG R) cells 29435139
Rh30 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for Rh30 cells 29435139
OHS-50 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for OHS-50 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
NB1643 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for NB1643 cells 29435139
SK-N-MC qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for SK-N-MC cells 29435139
SJ-GBM2 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for SJ-GBM2 cells 29435139
TC32 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for TC32 cells 29435139
Rh18 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for Rh18 cells 29435139
Saos-2 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for Saos-2 cells 29435139
Haga clic para ver más datos experimentales de líneas celulares

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

Peso molecular 480.52 Fórmula

C23H28N8O4

 Almacenamiento (Desde la fecha de recepción)
Nº CAS 1032568-63-0 Descargar SDF Almacenamiento de soluciones madre

Sinónimos BAY 80-6946 Smiles COC1=C(C=CC2=C3NCCN3C(=NC(=O)C4=CN=C(N=C4)N)N=C21)OCCCN5CCOCC5

Solubilidad (Solubility)

In vitro
Lote:

5%TFA : 8 mg/mL

DMSO : Insoluble
(El DMSO contaminado con humedad puede reducir la solubilidad. Usar DMSO fresco y anhidro.)

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
PI3Kα
(Cell-free assay)
0.5 nM
PI3Kδ
(Cell-free assay)
0.7 nM
PI3Kβ
(Cell-free assay)
3.7 nM
PI3Kγ
(Cell-free assay)
6.4 nM
In vitro

In both KPL4 cells and LPA-stimulated PC3 cells, BAY 80-6946 reduces pAKT levels. In a subset of human cancer cell lines with PIK3CA mutations and/or overexpression of HER2, BAY 80-6946 shows antiproliferative activity and induces apoptosis. [1] The combination of HER2-targeted therapies and BAY 80-6946 inhibits growth more effectively than either therapy used alone, and can restore sensitivity to trastuzumab and lapatinib in cells. [2]
Ensayo de quinasa
Ensayos bioquímicos de lipid quinasas
El efecto de BAY 80-6946 sobre la actividad de PI3Kα, PI3Kβ y PI3Kγ se mide mediante la inhibición de la incorporación de 33P en el fosfatidilinositol (PI) en placas MaxiSorp® de 384 pocillos recubiertas con 2 µg/pocillo de PI y fosfatidilserina (PS) (relación molar 1:1). En cada ensayo de isoforma de PI3K, se utilizan 9 µL de tampón de reacción (50 mM MOPSO, pH 7.0, 100 mM NaCl, 4 mM MgCl2, 0.1% BSA) que contienen 7.5 ng de proteína p110α o p110β truncada en el N-terminal con etiqueta His, o 25 ng de proteína p110γ humana purificada. La reacción se inicia añadiendo 5 µL de una solución de ATP 40 µM que contiene 20 µCi/mL de [33P]-ATP. Después de 2 horas de incubación a temperatura ambiente, la reacción se termina añadiendo 5 µL de una solución de EDTA 25 mM. Las placas se lavan y luego se añaden 25 µL de cóctel de centelleo Ultima Gold™. La radioactividad incorporada en el sustrato de PI inmovilizado se determina con un contador de centelleo líquido BetaPlate.
In vivo

In rat KPL4 or HCT116 tumor xenograft model, BAY 80-6946 (6 mg/kg, i.v.) induces 100% complete tumor regression. In nude mice with Lu7860 erlotinib-resistant, patient-derived NSCLC and MAXF1398 patient-derived luminal breast tumor models, BAY 80-6946 (14 mg/kg, i.v.) also causes tumor growth inhibition. [1]
Referencias

Aplicaciones (Applications)

Métodos Biomarcadores Imágenes PMID
Western blot p-FoxO4(T28) / p-S6(S235/236) / p-4E-BP1(S65) / p-4E-BP1(T37/46) / p-HER3(Y1197) / HER3 / p-IGF1Rβ/ IGF1R / p-HER2 / p-EGFR / p-STAT3 / p-ERK p-AKT / AKT / p-PRAS40(T246) / p-GSK3β(S9) / cleaved caspase-3 / cleaved caspase-7 / PI3K-p85
S2802-WB2
24436048
Growth inhibition assay Cell viability
S2802-viability
24436048

Información del ensayo clínico (Clinical Trial Information)

(datos de https://clinicaltrials.gov, actualizado el 2024-05-22)

Número NCT Reclutamiento Condiciones Patrocinador/Colaboradores Fecha de inicio Fases
NCT05082025 Active not recruiting
Endometrial Cancer|Ovarian Cancer
M.D. Anderson Cancer Center|Bayer
 September 27 2022 Phase 2
NCT05217914 Active not recruiting
Relapsed or Refractory Indolent Non-Hodgkin Lymphoma
Bayer
 July 1 2022 --
NCT04939272 Suspended
Recurrent Mantle Cell Lymphoma|Refractory Mantle Cell Lymphoma
City of Hope Medical Center|National Cancer Institute (NCI)
 June 29 2022 Phase 1|Phase 2
NCT04572763 Active not recruiting
Diffuse Large B Cell Lymphoma|Relapsed Diffuse Large B-Cell Lymphoma|Refractory Diffuse Large B-Cell Lymphoma
Dana-Farber Cancer Institute|AbbVie|Bayer
 September 8 2021 Phase 1|Phase 2
NCT04803123 Terminated
Leukemia Acute Lymphocytic
Dorothy Sipkins MD PhD|Bayer|Duke University
 June 21 2021 Early Phase 1