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PR-171 (Carfilzomib) Proteasome inhibitor

Name: PR-171 (Carfilzomib)
Brand: Selleck Chemicals
SKU: S2853
Rating: 5 (251 reviews)

Cat. No.: S2853

Carfilzomib (PR-171) is an irreversible proteasome inhibitor with IC50 of <5 nM in ANBL-6 cells, displayed preferential in vitro inhibitory potency against the ChT-L activity in the β5 subunit, but little or no effect on the PGPH and T-L activities. Carfilzomib activates prosurvival autophagy and induces cell apoptosis.

PR-171 (Carfilzomib) Proteasome inhibitor Chemical Structure

Estructura química

Peso molecular: 719.91

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Control de calidad (Quality Control)

Lote: Pureza: 99.75%

99.75

Dianas relacionadas	HDAC Caspase Secretase MMP HCV Protease Cysteine Protease Tyrosinase HIV Protease DPP Serine Protease
Otros Proteasome Inhibidores	MG132 Epoxomicin (BU-4061T) ONX-0914 (PR-957) Oprozomib Delanzomib VR23 PI-1840 Marizomib (Salinosporamide A) KSQ-4279 (USP1-IN-1) MG-115

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

Líneas celulares	Tipo de ensayo	Concentración	Tiempo de incubación	Descripción de la actividad	PMID
MM.1S	Growth Inhibition Assay	0-100 nM	48 h	IC50 = 10 nM	25312543
NCI-H929	Growth Inhibition Assay	0-100 nM	48 h	IC50 = 14 nM	25312543
SUDHL16	Apoptosis Asssay	2.5–3.5 nM	48 h	enhances the cell death co-treatment with ACY1215	25239935
SUDHL14	Apoptosis Asssay	2.5–3.5 nM	48 h	enhances the cell death co-treatment with ACY1215	25239935
U2932	Apoptosis Asssay	2.5–3.5 nM	48 h	enhances the cell death co-treatment with ACY1215	25239935
P-UMSCC-1	Growth Inhibition Assay			IC50=11.2 nM	24915039
R-UMSCC-1	Growth Inhibition Assay			IC50=2294 nM	24915039
P-Cal33	Growth Inhibition Assay			IC50=17.3 nM	24915039
R-Cal33	Growth Inhibition Assay			IC50=1112 nM	24915039
Jurkat	Growth Inhibition Assay	1-11nM	48 h	inhibits the cell proliferation co-treatment with vorinostat	24801128
Jurkat	Apoptosis Asssay	8 nM	24/48 h	induces apoptosis, caspase activation, and PARP cleavage co-treatment with vorinostat	24801128
UMSCC-22A	Apoptosis Asssay	200 nM	24 h	induce the cell apoptosis co-treatment with ONX 0912	22929803
UMSCC-22B	Apoptosis Asssay	200 nM	24 h	induce the cell apoptosis co-treatment with ONX 0912	22929803
1483	Apoptosis Asssay	200 nM	24 h	induce the cell apoptosis co-treatment with ONX 0912	22929803
UMSCC-1	Apoptosis Asssay	200 nM	24 h	induce the cell apoptosis co-treatment with ONX 0912	22929803
UMSCC-22A	Growth Inhibition Assay			IC50=38.7 ± 1.0 nM	22929803
UMSCC-22B	Growth Inhibition Assay			IC50=30.7 ± 9.3 nM	22929803
1483	Growth Inhibition Assay			IC50=50.5 ± 11.9 nM	22929803
UMSCC-1	Growth Inhibition Assay			IC50=34.6 ± 2.6 nM	22929803
Cal33	Growth Inhibition Assay			IC50=49.3 ± 8.9 nM	22929803
PCI-15A	Growth Inhibition Assay			IC50=70.4 ± 22.6 nM	22929803
PCI-15B	Growth Inhibition Assay			IC50=39.5 ± 11.0 nM	22929803
OSC-19	Growth Inhibition Assay			IC50=18.3 ± 4.2 nM	22929803
SUDHL16	Apoptosis Asssay	2.0-4.0 nM	48 h	induces cell death co-treatment with obatoclax	22411899
SUDHL16	Function Assay	2.5 nM	24 h	activates JNK, inactivates AKT, up-regulates Noxa, and induces γH2A.X co-treatment with obatoclax	22411899
Granta	Growth Inhibition Assay	0-4 nM	48 h	induce cell death co-treatment with HADCIs	21750224
SUDHL16	Growth Inhibition Assay	1-4 nM	36 h	induce cell death co-treatment with HADCIs	20233973
MOLT4	Function assay		1 hr	Inhibition of chymotrypsin-like activity of 20S proteasome in human MOLT4 cells after 1 hr by CellTiter-Glo luminescent assay, IC50 = 0.0051 μM.	19348473
MESSA	Cytotoxicity assay		72 hrs	Cytotoxicity against human MESSA cells assessed as cell viability after 72 hrs by CellTiter-Glo luminescent assay, IC50 = 0.018 μM.	19348473
MESSA	Cytotoxicity assay		72 hrs	Cytotoxicity against multidrug resistance transporter expressing doxorubicin resistant human MESSA cells assessed as cell viability after 72 hrs by CellTiter-Glo luminescent assay, IC50 = 0.413 μM.	19348473
RPMI8226	Cytotoxicity assay		72 hrs	Cytotoxic activity against human RPMI8226 cells after 72 hrs by MTS assay, IC50 = 0.01319 μM.	24767818
NCI-H929	Cytotoxicity assay		72 hrs	Cytotoxic activity against human NCI-H929 cells after 72 hrs by MTS assay, IC50 = 0.02132 μM.	24767818
CCRF-CEM	Antiproliferative assay		72 hrs	Antiproliferative activity against human CCRF-CEM cells after 72 hrs by oxyluciferin luminescence assay, IC50 = 0.0061 μM.	26231162
RPMI8266	Antiproliferative assay		72 hrs	Antiproliferative activity against human RPMI8266 cells after 72 hrs by oxyluciferin luminescence assay, IC50 = 0.0139 μM.	26231162
HCT116	Antiproliferative assay		72 hrs	Antiproliferative activity against human HCT116 cells after 72 hrs by oxyluciferin luminescence assay, IC50 = 0.0193 μM.	26231162
A431	Antiproliferative assay		72 hrs	Antiproliferative activity against human A431 cells after 72 hrs by oxyluciferin luminescence assay, IC50 = 0.0238 μM.	26231162
TOV21G	Antiproliferative assay		72 hrs	Antiproliferative activity against human TOV21G cells after 72 hrs by oxyluciferin luminescence assay, IC50 = 0.0238 μM.	26231162
RKO	Antiproliferative assay		72 hrs	Antiproliferative activity against human RKO cells after 72 hrs by oxyluciferin luminescence assay, IC50 = 0.0271 μM.	26231162
MM1S	Antiproliferative assay		72 hrs	Antiproliferative activity against human MM1S cells measured after 72 hrs by MTS assay, IC50 = 0.0015 μM.	27765408
RPMI8226	Antiproliferative assay		72 hrs	Antiproliferative activity against human RPMI8226 cells measured after 72 hrs by MTS assay, IC50 = 0.0132 μM.	27765408
LCL	Cytotoxicity assay		48 hrs	Cytotoxicity against human LCL cells harboring wild type p53 assessed as reduction in cell viability after 48 hrs by 7AAD-staining based FACS analysis, LD50 = 0.03 μM.	27994734
RD-ES	Cytotoxicity assay		48 hrs	Cytotoxicity against human RD-ES cells harboring p53 mutant assessed as reduction in cell viability after 48 hrs by 7AAD-staining based FACS analysis, LD50 = 0.043 μM.	27994734
U266	Cytotoxicity assay		48 hrs	Cytotoxicity against human U266 cells harboring mutant p53 assessed as reduction in cell viability after 48 hrs by 7AAD-staining based FACS analysis, LD50 = 0.06 μM.	27994734
WE68	Cytotoxicity assay		48 hrs	Cytotoxicity against human WE68 cells harboring wild type p53 assessed as reduction in cell viability after 48 hrs by 7AAD-staining based FACS analysis, LD50 = 0.08 μM.	27994734
IMR90	Cytotoxicity assay		48 hrs	Cytotoxicity against human IMR90 cells harboring wild type p53 assessed as reduction in cell viability after 48 hrs by 7AAD-staining based FACS analysis, LD50 = 0.13 μM.	27994734
MCF10A	Cytotoxicity assay		48 hrs	Cytotoxicity against human MCF10A cells harboring wild type p53 assessed as reduction in cell viability after 48 hrs by 7AAD-staining based FACS analysis, LD50 = 0.32 μM.	27994734
SKOV3	Cytotoxicity assay		48 hrs	Cytotoxicity against p53 deficient human SKOV3 cells assessed as reduction in cell viability after 48 hrs by 7AAD-staining based FACS analysis, LD50 = 0.32 μM.	27994734
MDA-MB-468	Cytotoxicity assay		48 hrs	Cytotoxicity against human MDA-MB-468 cells harboring mutant p53 assessed as reduction in cell viability after 48 hrs by 7AAD-staining based FACS analysis, LD50 = 0.33 μM.	27994734
HNDF	Cytotoxicity assay		48 hrs	Cytotoxicity against HNDF cells harboring wild type p53 assessed as reduction in cell viability after 48 hrs by 7AAD-staining based FACS analysis, LD50 = 0.35 μM.	27994734
KGN	Cytotoxicity assay		48 hrs	Cytotoxicity against human KGN cells harboring wild type p53 assessed as reduction in cell viability after 48 hrs by 7AAD-staining based FACS analysis, LD50 = 0.45 μM.	27994734
MCF7	Cytotoxicity assay		48 hrs	Cytotoxicity against human MCF7 cells harboring wild type p53 assessed as reduction in cell viability after 48 hrs by 7AAD-staining based FACS analysis, LD50 = 4.5 μM.	27994734
MCF7	Function assay	35 nM	4 hrs	Inhibition of 26S proteasome in human MCF7 cells assessed as accumulation of high molecular weight polyubiquitin-conjugated proteins at 35 nM after 4 hrs by Western blot analysis	27994734
MDA-MB-468	Function assay	35 nM	4 hrs	Inhibition of 26S proteasome in human MDA-MB-468 cells assessed as accumulation of high molecular weight polyubiquitin-conjugated proteins at 35 nM after 4 hrs by Western blot analysis	27994734
MM1S	Cytotoxicity assay		72 hrs	Cytotoxicity against human MM1S cells measured after 72 hrs by MTS assay, IC50 = 0.0015 μM.	28027531
RPMI8226	Cytotoxicity assay		72 hrs	Cytotoxicity against human RPMI8226 cells measured after 72 hrs by MTS assay, IC50 = 0.0132 μM.	28027531
TC32	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for TC32 cells	29435139
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
Saos-2	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Saos-2 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
OHS-50	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for OHS-50 cells	29435139
BT-12	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for BT-12 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
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
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
Rh30	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Rh30 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
fibroblast cells	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for control Hh wild type fibroblast 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
SK-N-SH	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Orthogonal 3D viability screen for SK-N-SH cells	29435139
Daoy	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Orthogonal 3D viability screen for Daoy cells	29435139
TC32	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Orthogonal 3D caspase screen for TC32 cells	29435139
TC32	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Orthogonal 3D viability screen for TC32 cells	29435139
MG 63 (6-TG R)	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Orthogonal 3D viability screen for MG 63 (6-TG R) 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
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
SJ-GBM2	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Orthogonal 3D viability screen for SJ-GBM2 cells	29435139
RD	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Orthogonal 3D viability screen for RD cells	29435139
ANBL-6	Function assay			Inhibition of 20S proteasome activity in human ANBL-6 cells, IC50 = 0.01 μM.	29652143
MCF7	Cytotoxicity assay		48 hrs	Cytotoxicity against human MCF7 cells after 48 hrs by MTT assay, IC50 = 0.0041 μM.	30165344
MDA-MB-231	Cytotoxicity assay		48 hrs	Cytotoxicity against human MDA-MB-231 cells after 48 hrs by MTT assay, IC50 = 0.0044 μM.	30165344
RPMI8226	Cytotoxicity assay		48 hrs	Cytotoxicity against human RPMI8226 cells after 48 hrs by MTT assay, IC50 = 0.0067 μM.	30165344
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Información química, almacenamiento y estabilidad (Chemical Information, Storage & Stability)

Peso molecular	719.91	Fórmula	C₄₀H₅₇N₅O₇	Almacenamiento (Desde la fecha de recepción)	3 años-20°Cpolvo
Nº CAS	868540-17-4	Descargar SDF		Almacenamiento de soluciones madre	1 año-80°Cen disolvente 1 mes-20°Cen disolvente
Sinónimos	N/A			Smiles	CC(C)CC(C(=O)C1(CO1)C)NC(=O)C(CC2=CC=CC=C2)NC(=O)C(CC(C)C)NC(=O)C(CCC3=CC=CC=C3)NC(=O)CN4CCOCC4

Solubilidad (Solubility)

In vitro
Lote:

DMSO : 100 mg/mL (138.9 mM)
(El DMSO contaminado con humedad puede reducir la solubilidad. Usar DMSO fresco y anhidro.)

Ethanol : 50 mg/mL

Water : Insoluble

Calculadora de Molaridad

Masa	Concentración	Volumen	Peso molecular
=	×	×

Calculadora de Dilución Calculadora de Peso Molecular

In vivo Lote:
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Clear solution	2%DMSO 1 30%PEG300 2 2%TWEEN80 3 66%ddH2O Validado por los laboratorios Selleck. Si necesita ajustes en esta formulación, contacte con nuestro equipo de ventas para pruebas personalizadas.	1.000mg/ml (1.39mM)	Taking the 1 mL working solution as an example, add 20 μL of 50 mg/ml clarified DMSO stock solution to 300 μL of PEG300, mix evenly to clarify it; add 20 μL of Tween80 to the above system, mix evenly to clarify; then continue to add 660 μL of ddH2O to adjust the volume to 1 mL. The mixed solution should be used immediately for optimal results.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Clear solution	2%DMSO 1 30%PEG300 2 2%Tween80 3 66%ddH2O Validado por los laboratorios Selleck. Si necesita ajustes en esta formulación, contacte con nuestro equipo de ventas para pruebas personalizadas.	1.000mg/ml (1.39mM)	Taking the 1 mL working solution as an example, add 20 μL of 50 mg/ml clarified DMSO stock solution to 300 μL of PEG300, mix evenly to clarify it; add 20 μL of Tween80 to the above system, mix evenly to make it clear; then continue to add 660 μL of ddH2O to adjust the volume to 1 mL. The mixed solution should be used immediately for optimal results.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.

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)

Dosis: mg/kg Peso promedio de los animales: g Volumen de dosificación por animal:μL Número de animales:

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	Proteasome (ANBL-6 cells) 5 nM
In vitro	El Carfilzomib (PR-171) inhibe la proliferación en una variedad de líneas celulares y células neoplásicas derivadas de pacientes, incluido el mieloma múltiple, e indujo vías de señalización apoptótica intrínsecas y extrínsecas y la activación de la cinasa c-Jun-N-terminal (JNK). Revela una actividad anti-MM mejorada, supera la resistencia a otros agentes y actúa sinérgicamente con (Dex). Este compuesto muestra una potencia inhibidora in vitro preferencial contra la actividad ChT-L en la subunidad β5, con más del 80% de inhibición a dosis de 10 nM. La exposición corta a Carfilzomib en dosis bajas conduce a una especificidad de unión preferencial para el β5 Proteasome constitutivo 20S y las subunidades del inmunoproteasoma β5i. La medición de la actividad de la caspasa en células ANBL-6 pulsadas con él revela aumentos sustanciales en la actividad de la caspasa-8, caspasa-9 y caspasa-3 después de 8 horas, lo que da un aumento de 3.2, 3.9 y 6.9 veces, respectivamente, sobre las células control después de 8 horas. En las células tratadas con Carfilzomib pulsado, la integridad de la membrana mitocondrial disminuye al 41% (Q1 + Q2), en comparación con el 75% en las células control tratadas con vehículo. En otro estudio, también ha demostrado eficacia preclínica contra malignidades hematológicas y sólidas. Inhibe directamente la formación de osteoclastos y la resorción ósea.
Ensayo de quinasa	Ensayo de inmunoadsorción ligado a enzimas para el perfil de subunidades de carfilzomib
Ensayo de quinasa	Las células ANBL-6 (2 × 10⁶/pozo) se siembran en placas de 96 pozos y se tratan con Carfilzomib (PR-171) a dosis de 0,001 a 10 μM durante 1 hora. Luego se lisan las células (20 mM Tris-HCl, 0,5 mM EDTA) y los lisados clarificados se transfieren a placas de reacción en cadena de la polimerasa (PCR). Se genera una curva estándar utilizando lisados de células ANBL-6 no tratadas, comenzando con una concentración de 6 μg de proteína/μL. Se añade la sonda del sitio activo [biotina-(CH2)4-Leu-Leu-Leu-epoxicetona; 20 μM] y se incuba a temperatura ambiente durante 1 hora. Luego, los lisados celulares se desnaturalizan añadiendo un 1% de dodecil sulfato de sodio (SDS) y calentando a 100°C, seguido de la mezcla con 20 μL por pozo de perlas de estreptavidina-sefarosa de alto rendimiento en una placa multiscreen DV de 96 pozos y se incuban durante 1 hora. Estas perlas se lavan luego con tampón de ensayo de inmunoadsorción ligado a enzimas (ELISA) (PBS, 1% de albúmina de suero bovino y 0,1% de Tween-20) y se incuban durante la noche a 4°C en un agitador de placas con anticuerpos para las subunidades del Proteasome. Los anticuerpos utilizados incluyeron monoclonales de ratón anti-β1, anti-β2, anti-β1i y anti-β5i, policlonales de cabra anti-β2i y policlonales de conejo anti-β5 (antisueros purificados por afinidad contra el péptido KLH-CWIRVSSDNVADLHDKYS). Las perlas se lavan y se incuban durante 2 horas con anticuerpos secundarios conjugados con peroxidasa de rábano picante de cabra anti-conejo, cabra anti-ratón o conejo anti-cabra. Después del lavado, las perlas se desarrollan utilizando el sustrato de picochemiluminiscencia Supersignal ELISA. Se realiza la detección luminiscente. La luminiscencia bruta se convierte a μg/mL mediante comparación con la curva estándar y se expresa como el % de inhibición relativa al control del vehículo. Los ajustes de curva se generan utilizando la siguiente ecuación de dosis-respuesta no sigmoidal: Y = Fondo + (Superior-Fondo)/(1 + 10̂((LogEC50 − X) × Pendiente)), donde X es el logaritmo de la concentración, Y es el % de inhibición y EC50 es la dosis de este compuesto que muestra un efecto del 50 %.
In vivo	Carfilzomib (PR-171) reduce moderadamente el crecimiento tumoral en un modelo de xenoinjerto in vivo. Disminuye eficazmente la viabilidad de las células de mieloma múltiple después de un tratamiento continuo o transitorio. Este compuesto también aumenta el volumen óseo trabecular, disminuye la resorción ósea y mejora la formación ósea en ratones sin tumor.
Referencias	[1] https://pubmed.ncbi.nlm.nih.gov/17591945/ [2] https://pubmed.ncbi.nlm.nih.gov/21247387/ [3] https://pubmed.ncbi.nlm.nih.gov/22763387/ [4] https://pubmed.ncbi.nlm.nih.gov/21750224/

Aplicaciones (Applications)

Métodos	Biomarcadores	Imágenes	PMID
Western blot	pERK / ERK / pSTAT5 / STAT5 / pPI3K / PI3K caspase-9 / caspase-8 c-PARP / PARP / caspase-3 Bcl-2 / Bcl-Xl / Mcl-1 / Bik / Bim / Bax / Bak Atg5 / Atg12 / Beclin-1 / LC3-II Noxa / Bik / Puma / Mcl-1 EGFR / HER2 / ER alpha / p-Akt(Ser473) / Akt / p-ERK / ERK / p53 BDP1 / HER2(Tyr1248) / HER2(Tyr1221/Tyr1222) / PARP1 / caspase-7 / p53 Mut HLA class I		24590311
Growth inhibition assay	Cell viability		27655642

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
NCT05552976	Recruiting	Relapsed or Refractory Multiple Myeloma	Bristol-Myers Squibb	January 10 2023	Phase 3
NCT05675449	Recruiting	Multiple Myeloma	Pfizer	December 14 2022	Phase 1
NCT05041933	Unknown status	Hematological Diseases	University Hospital Limoges	September 15 2021	--

Preguntas frecuentes (Frequently Asked Questions)

Pregunta 1:
How should I prepare a solution of it for an ongoing in vivo study?

Respuesta:
It can be dissolved in 2% DMSO/30% PEG 300/dd H₂O at 10 mg/ml as a suspension, and can be dissolved in 2% DMSO/castor oil at 10 mg/ml as a clear solution.

C1=C0/X	C1:	LOG(C1):
C2=C1/X	C2:	LOG(C2):
C3=C2/X	C3:	LOG(C3):
C4=C3/X	C4:	LOG(C4):
C5=C4/X	C5:	LOG(C5):
C6=C5/X	C6:	LOG(C6):
C7=C6/X	C7:	LOG(C7):
C8=C7/X	C8:	LOG(C8):