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PR-171 (Carfilzomib) Proteasome inhibiteur

Name: PR-171 (Carfilzomib)
Brand: Selleck Chemicals
SKU: S2853
Rating: 5 (249 reviews)

Réf. CatalogueS2853

Le Carfilzomib (PR-171) est un inhibiteur irréversible du protéasome avec une IC50 de <5 nM dans les cellules ANBL-6, il a montré une puissance inhibitrice préférentielle in vitro contre l'activité ChT-L dans la sous-unité β5, mais peu ou pas d'effet sur les activités PGPH et T-L. Le Carfilzomib active l'autophagy pro-survie et induit l'apoptosis cellulaire.

PR-171 (Carfilzomib) Proteasome inhibiteur Chemical Structure

Structure chimique

Poids moléculaire: 719.91

Aller à

Contrôle Qualité

Lot : Pureté : 99.75%

99.75

Cibles apparentées	HDAC Caspase Secretase MMP HCV Protease Cysteine Protease DPP Tyrosinase HIV Protease Serine Protease
Autre Proteasome Inhibiteurs	MG132 Celastrol Epoxomicin (BU-4061T) ONX-0914 (PR-957) Oprozomib Delanzomib VR23 Marizomib (Salinosporamide A) PI-1840 KSQ-4279 (USP1-IN-1)

Culture cellulaire, traitement et concentration de travail

Lignées cellulaires	Type dessai	Concentration	Temps dincubation	Description de lactivité	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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Informations chimiques, stockage et stabilité

Poids moléculaire	719.91	Formule	C₄₀H₅₇N₅O₇	Stockage (À compter de la date de réception)	3 ans-20°Cpoudre
N° CAS	868540-17-4	Télécharger le SDF		Stockage des solutions mères	1 an-80°Cen solvant 1 mois-20°Cen solvant
Synonymes	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

Solubilité

In vitro
Lot:

DMSO : 100 mg/mL (138.9 mM)
(Le DMSO contaminé par lhumidité peut réduire la solubilité. Utiliser du DMSO frais et anhydre.)

Ethanol : 50 mg/mL

Water : Insoluble

Calculateur de molarité

Masse	Concentration	Volume	Poids moléculaire
=	×	×

Calculateur de dilution Calculateur de poids moléculaire

In vivo Lot:
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 Validé par les laboratoires Selleck. Si vous avez besoin dajustements à cette formulation, contactez notre équipe commerciale pour des tests personnalisés.	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 Validé par les laboratoires Selleck. Si vous avez besoin dajustements à cette formulation, contactez notre équipe commerciale pour des tests personnalisés.	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.

Calculateur de formulation in vivo (Solution claire)

Étape 1 : Saisir les informations ci-dessous (Recommandé : Un animal supplémentaire pour tenir compte des pertes pendant lexpérience)

Dosage : mg/kg Poids moyen des animaux : g Volume de dosage par animal :μL Nombre danimaux :

Étape 2 : Saisir la formulation in vivo (Ceci est seulement le calculateur, pas la formulation. Veuillez nous contacter dabord sil ny a pas de formulation in vivo dans la section Solubilité.)

% DMSO + % + % Tween 80 + % ddH₂O

%DMSO+ %

Résultats du calcul :

Concentration de travail : mg/ml;

Méthode de préparation du liquide maître DMSO : mg médicament prédissous dans μL DMSO ( Concentration du liquide maître mg/mL, Veuillez nous contacter dabord si la concentration dépasse la solubilité du DMSO du lot de médicament. )

Méthode de préparation de la formulation in vivo : Prendre μL DMSO liquide maître, puis ajouterμL PEG300, mélanger et clarifier, puis ajouterμL Tween 80, mélanger et clarifier, puis ajouter μL ddH₂O, mélanger et clarifier.

Méthode de préparation de la formulation in vivo : Prendre μL DMSO liquide maître, puis ajouter μL Huile de maïs, mélanger et clarifier.

Note : 1. Veuillez vous assurer que le liquide est clair avant dajouter le solvant suivant.
2. Assurez-vous dajouter le(s) solvant(s) dans lordre. Vous devez vous assurer que la solution obtenue, lors de lajout précédent, est une solution claire avant de procéder à lajout du solvant suivant. Des méthodes physiques telles que le vortex, les ultrasons ou le bain-marie chaud peuvent être utilisées pour faciliter la dissolution.

Mécanisme daction

Targets/IC₅₀/Ki	Proteasome (ANBL-6 cells) 5 nM
In vitro	Le Carfilzomib (PR-171) inhibe la prolifération dans une variété de lignées cellulaires et de cellules néoplasiques dérivées de patients, y compris le myélome multiple, et a induit des voies de signalisation apoptotique intrinsèques et extrinsèques et l'activation de la kinase c-Jun-N-terminale (JNK). Il révèle une activité anti-MM améliorée, surmonte la résistance à d'autres agents et agit en synergie avec (Dex). Ce composé montre une puissance inhibitrice in vitro préférentielle contre l'activité ChT-L dans la sous-unité β5, avec plus de 80 % d'inhibition à des doses de 10 nM. Une courte exposition à une faible dose de Carfilzomib entraîne une spécificité de liaison préférentielle pour le β5 Proteasome constitutif 20S et les sous-unités immunoprotéasomes β5i. La mesure de l'activité des caspases dans les cellules ANBL-6 pulsées avec ce composé révèle des augmentations substantielles de l'activité des caspases-8, caspase-9 et caspase-3 après 8 heures, donnant respectivement une augmentation de 3,2, 3,9 et 6,9 fois par rapport aux cellules témoins après 8 heures. Dans les cellules traitées par pulsation de carfilzomib, l'intégrité de la membrane mitochondriale est diminuée à 41 % (Q1 + Q2), comparativement à 75 % dans les cellules témoins traitées par véhicule. Dans une autre étude, il a également montré une efficacité préclinique contre les hémopathies malignes et les tumeurs solides. Il inhibe directement la formation des ostéoclastes et la résorption osseuse.
Essai kinase	Test immunoenzymatique pour le profilage des sous-unités du Carfilzomib
Essai kinase	Les cellules ANBL-6 (2 × 10⁶/puits) sont ensemencées dans des plaques à 96 puits et traitées avec du Carfilzomib (PR-171) à des doses allant de 0,001 à 10 μM pendant 1 heure. Les cellules sont ensuite lysées (20 mM Tris-HCl, 0,5 mM EDTA), et les lysats clarifiés sont transférés dans des plaques de réaction en chaîne par polymérase (PCR). Une courbe standard est générée en utilisant des lysats de cellules ANBL-6 non traitées, en commençant par une concentration de 6 μg de protéine/μL. La sonde de site actif [biotine-(CH2)4-Leu-Leu-Leu-époxycétone; 20 μM] est ajoutée et incubée à température ambiante pendant 1 heure. Les lysats cellulaires sont ensuite dénaturés en ajoutant 1 % de dodécylsulfate de sodium (SDS) et en chauffant à 100 °C, puis en mélangeant avec 20 μL par puits de billes de streptavidine-sépharose haute performance dans une plaque multiscreen DV à 96 puits et incubées pendant 1 heure. Ces billes sont ensuite lavées avec un tampon d'essai immunoenzymatique (ELISA) (PBS, 1 % d'albumine de sérum bovin et 0,1 % de Tween-20) et incubées pendant la nuit à 4 °C sur un agitateur de plaques avec des anticorps contre les sous-unités du Proteasome. Les anticorps utilisés comprenaient des anticorps monoclonaux de souris anti-β1, anti-β2, anti-β1i et anti-β5i, des anticorps polyclonaux de chèvre anti-β2i et des anticorps polyclonaux de lapin anti-β5 (antisérum purifié par affinité contre le peptide KLH-CWIRVSSDNVADLHDKYS). Les billes sont lavées et incubées pendant 2 heures avec des anticorps secondaires conjugués à la peroxydase de raifort de chèvre anti-lapin, de chèvre anti-souris ou de lapin anti-chèvre. Après lavage, les billes sont développées à l'aide du substrat de picochemiluminescence Supersignal ELISA. La détection luminescente est effectuée. La luminescence brute est convertie en μg/mL par comparaison avec la courbe standard et exprimée en % d'inhibition par rapport au contrôle véhicule. Les ajustements de courbe sont générés à l'aide de l'équation de dose-réponse non sigmoïdale suivante : Y = Bas + (Haut-Bas)/(1 + 10̂((LogEC50 − X) × HillSlope)), où X est le logarithme de la concentration, Y est le % d'inhibition et EC50 est la dose de ce composé montrant un effet de 50 %.
In vivo	Le Carfilzomib (PR-171) réduit modérément la croissance tumorale dans un modèle de xénogreffe in vivo. Il diminue efficacement la viabilité des cellules du myélome multiple après un traitement continu ou transitoire. Ce composé augmente également le volume osseux trabéculaire, diminue la résorption osseuse et améliore la formation osseuse chez les souris sans tumeur.
Références	[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/

Applications

Méthodes	Biomarqueurs	Images	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

Informations sur lessai clinique

(données du https://clinicaltrials.gov, mis à jour le 2024-05-22)

Numéro NCT	Recrutement	Conditions	Promoteur/Collaborateurs	Date de début	Phases
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	--

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Instructions de manipulation

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Foire aux questions

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

Réponse :
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):