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Carfilzomib [868540-17-4]

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Referencia HY-10455-5mg

embalaje : 5mg

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Teléfono : +1 850 650 7790

Marca : MedChemExpress

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Contact local distributor :

Teléfono : +1 850 650 7790

Descripciòn

Carfilzomib (PR-171) is an irreversible proteasome inhibitor with an IC₅₀ of 5 nM in ANBL-6 and RPMI 8226 cells.

IC₅₀ & Target

IC50: 5 nM (Proteasome)

Cellular Effect

Cell Line	Type	Value	Description	References
A-431	IC₅₀	23.8 nM Compound: Carfilzomib	Antiproliferative activity against human A431 cells after 72 hrs by oxyluciferin luminescence assay Antiproliferative activity against human A431 cells after 72 hrs by oxyluciferin luminescence assay	[PMID: 26231162]
A549	IC₅₀	43.3 nM Compound: Carfilzomib	Antiproliferative activity against human A549 cells after 72 hrs by MTS assay Antiproliferative activity against human A549 cells after 72 hrs by MTS assay	[PMID: 30639896]
ARPE-19	IC₅₀	0.058 μM Compound: Carfilzomib	Cytotoxicity against human ARPE-19 cells assessed as reduction in cell viability incubated for 96 hrs by CellTiter 96 Aqueous One Solution Cell Proliferation Assay Cytotoxicity against human ARPE-19 cells assessed as reduction in cell viability incubated for 96 hrs by CellTiter 96 Aqueous One Solution Cell Proliferation Assay	[PMID: 38636481]
CCRF-CEM	IC₅₀	6.1 nM Compound: Carfilzomib	Antiproliferative activity against human CCRF-CEM cells after 72 hrs by oxyluciferin luminescence assay Antiproliferative activity against human CCRF-CEM cells after 72 hrs by oxyluciferin luminescence assay	[PMID: 26231162]
HCT-116	IC₅₀	19.3 nM Compound: Carfilzomib	Antiproliferative activity against human HCT116 cells after 72 hrs by oxyluciferin luminescence assay Antiproliferative activity against human HCT116 cells after 72 hrs by oxyluciferin luminescence assay	[PMID: 26231162]
HCT-116	IC₅₀	9.6 nM Compound: Carfilzomib	Antiproliferative activity against human HCT116 cells after 72 hrs by MTS assay Antiproliferative activity against human HCT116 cells after 72 hrs by MTS assay	[PMID: 30639896]
HEK293	IC₅₀	92.1 μM Compound: Kyprolis(R)	Inhibition of human ERG in HEK293 cells assessed as effect on QT interval Inhibition of human ERG in HEK293 cells assessed as effect on QT interval	[PMID: 31383629]
LP-1	IC₅₀	22.7 nM Compound: Carfilzomib	Antiproliferative activity against human LP-1 cells after 72 hrs by MTS assay Antiproliferative activity against human LP-1 cells after 72 hrs by MTS assay	[PMID: 30639896]
MCF7	IC₅₀	0.0041 μM Compound: Cfz	Cytotoxicity against human MCF7 cells after 48 hrs by MTT assay Cytotoxicity against human MCF7 cells after 48 hrs by MTT assay	[PMID: 30165344]
MDA-MB-231	IC₅₀	0.0044 μM Compound: Cfz	Cytotoxicity against human MDA-MB-231 cells after 48 hrs by MTT assay Cytotoxicity against human MDA-MB-231 cells after 48 hrs by MTT assay	[PMID: 30165344]
MES-SA	IC₅₀	18 nM Compound: 2	Cytotoxicity against human MESSA cells assessed as cell viability after 72 hrs by CellTiter-Glo luminescent assay Cytotoxicity against human MESSA cells assessed as cell viability after 72 hrs by CellTiter-Glo luminescent assay	[PMID: 19348473]
MES-SA	IC₅₀	413 nM Compound: 2	Cytotoxicity against multidrug resistance transporter expressing doxorubicin resistant human MESSA cells assessed as cell viability after 72 hrs by CellTiter-Glo luminescent assay Cytotoxicity against multidrug resistance transporter expressing doxorubicin resistant human MESSA cells assessed as cell viability after 72 hrs by CellTiter-Glo luminescent assay	[PMID: 19348473]
MGC-803	IC₅₀	934 nM Compound: Carfilzomib	Antiproliferative activity against human MGC803 cells after 72 hrs by MTS assay Antiproliferative activity against human MGC803 cells after 72 hrs by MTS assay	[PMID: 30639896]
MM1.S	IC₅₀	<1 nM Compound: 2	Antiproliferative activity against human MM1S cells after 72 hrs by MTS assay Antiproliferative activity against human MM1S cells after 72 hrs by MTS assay	[PMID: 30611983]
MM1.S	IC₅₀	1.5 nM Compound: Carfilzomib	Antiproliferative activity against human MM1S cells measured after 72 hrs by MTS assay Antiproliferative activity against human MM1S cells measured after 72 hrs by MTS assay	[PMID: 27765408]
MM1.S	IC₅₀	1.5 nM Compound: Carfilzomib	Cytotoxicity against human MM1S cells measured after 72 hrs by MTS assay Cytotoxicity against human MM1S cells measured after 72 hrs by MTS assay	[PMID: 28027531]
MM1.S	IC₅₀	14.35 nM Compound: Carfilzomib	Antiproliferative activity against human MM1.S cells assessed as cell growth inhibition measured after 72 hrs by MTT assay Antiproliferative activity against human MM1.S cells assessed as cell growth inhibition measured after 72 hrs by MTT assay	[PMID: 33223460]
MM1.S	IC₅₀	2.3 nM Compound: Carfilzomib	Antiproliferative activity against human MM1S cells after 72 hrs by MTS assay Antiproliferative activity against human MM1S cells after 72 hrs by MTS assay	[PMID: 30639896]
MOLT-4	IC₅₀	5.1 nM Compound: 2	Inhibition of chymotrypsin-like activity of 20S proteasome in human MOLT4 cells after 1 hr by CellTiter-Glo luminescent assay Inhibition of chymotrypsin-like activity of 20S proteasome in human MOLT4 cells after 1 hr by CellTiter-Glo luminescent assay	[PMID: 19348473]
NCI-H23	IC₅₀	0.018 μM Compound: Cfz	Cytotoxicity against human NCI-H23 cells after 72 hrs by CellTiter 96 AQueous one solution cell proliferation assay Cytotoxicity against human NCI-H23 cells after 72 hrs by CellTiter 96 AQueous one solution cell proliferation assay	[PMID: 30964987]
NCI-H727	IC₅₀	0.6102 μM Compound: Cfz	Cytotoxicity against human NCI-H727 cells after 72 hrs by CellTiter 96 AQueous one solution cell proliferation assay Cytotoxicity against human NCI-H727 cells after 72 hrs by CellTiter 96 AQueous one solution cell proliferation assay	[PMID: 30964987]
NCI-H929	IC₅₀	116.1 nM Compound: Carfilzomib	Antiproliferative activity against human NCI-H929 cells after 72 hrs by MTS assay Antiproliferative activity against human NCI-H929 cells after 72 hrs by MTS assay	[PMID: 30639896]
NCI-H929	IC₅₀	13.9 nM Compound: Carfilzomib	Antiproliferative activity against human NCI-H929 cells assessed as cell growth inhibition measured after 72 hrs by MTT assay Antiproliferative activity against human NCI-H929 cells assessed as cell growth inhibition measured after 72 hrs by MTT assay	[PMID: 33223460]
NCI-H929	IC₅₀	21.32 nM Compound: Carfilzomib	Cytotoxic activity against human NCI-H929 cells after 72 hrs by MTS assay Cytotoxic activity against human NCI-H929 cells after 72 hrs by MTS assay	[PMID: 24767818]
PC-3	IC₅₀	23.9 nM Compound: Carfilzomib	Antiproliferative activity against human PC3 cells after 72 hrs by MTS assay Antiproliferative activity against human PC3 cells after 72 hrs by MTS assay	[PMID: 30639896]
RKO	IC₅₀	27.1 nM Compound: Carfilzomib	Antiproliferative activity against human RKO cells after 72 hrs by oxyluciferin luminescence assay Antiproliferative activity against human RKO cells after 72 hrs by oxyluciferin luminescence assay	[PMID: 26231162]
RPMI-8226	IC₅₀	0.0067 μM Compound: Cfz	Cytotoxicity against human RPMI8226 cells after 48 hrs by MTT assay Cytotoxicity against human RPMI8226 cells after 48 hrs by MTT assay	[PMID: 30165344]
RPMI-8226	IC₅₀	0.007 μM Compound: Cfz	Cytotoxicity against human RPMI8226 cells after 72 hrs by CellTiter 96 AQueous one solution cell proliferation assay Cytotoxicity against human RPMI8226 cells after 72 hrs by CellTiter 96 AQueous one solution cell proliferation assay	[PMID: 30964987]
RPMI-8226	IC₅₀	13.19 nM Compound: Carfilzomib	Cytotoxic activity against human RPMI8226 cells after 72 hrs by MTS assay Cytotoxic activity against human RPMI8226 cells after 72 hrs by MTS assay	[PMID: 24767818]
RPMI-8226	IC₅₀	13.2 nM Compound: Carfilzomib	Antiproliferative activity against human RPMI8226 cells measured after 72 hrs by MTS assay Antiproliferative activity against human RPMI8226 cells measured after 72 hrs by MTS assay	[PMID: 27765408]
RPMI-8226	IC₅₀	13.2 nM Compound: Carfilzomib	Cytotoxicity against human RPMI8226 cells measured after 72 hrs by MTS assay Cytotoxicity against human RPMI8226 cells measured after 72 hrs by MTS assay	[PMID: 28027531]
RPMI-8226	IC₅₀	14.1 nM Compound: Carfilzomib	Antiproliferative activity against human RPMI-8226 cells assessed as cell growth inhibition measured after 72 hrs by MTT assay Antiproliferative activity against human RPMI-8226 cells assessed as cell growth inhibition measured after 72 hrs by MTT assay	[PMID: 33223460]
RPMI-8226	IC₅₀	2 nM Compound: 2	Antiproliferative activity against human RPMI8226 cells after 72 hrs by MTS assay Antiproliferative activity against human RPMI8226 cells after 72 hrs by MTS assay	[PMID: 30611983]
RPMI-8226	IC₅₀	2.1 nM Compound: Carfilzomib	Antiproliferative activity against human RPMI8226 cells after 72 hrs by MTS assay Antiproliferative activity against human RPMI8226 cells after 72 hrs by MTS assay	[PMID: 30639896]
RPMI-8226	IC₅₀	39.1 nM Compound: Kyprolis(R)	Cytotoxicity against human RPMI8226 cells assessed as cell viability measured after 72 hrs by celltiter96 aqueous cell proliferation assay Cytotoxicity against human RPMI8226 cells assessed as cell viability measured after 72 hrs by celltiter96 aqueous cell proliferation assay	[PMID: 31383629]
TOV21G	IC₅₀	23.8 nM Compound: Carfilzomib	Antiproliferative activity against human TOV21G cells after 72 hrs by oxyluciferin luminescence assay Antiproliferative activity against human TOV21G cells after 72 hrs by oxyluciferin luminescence assay	[PMID: 26231162]
U-266	IC₅₀	35.7 nM Compound: Kyprolis(R)	Cytotoxicity against human U266B1 cells assessed as cell viability measured after 72 hrs by celltiter96 aqueous cell proliferation assay Cytotoxicity against human U266B1 cells assessed as cell viability measured after 72 hrs by celltiter96 aqueous cell proliferation assay	[PMID: 31383629]

In Vitro

Carfilzomib displays preferential in vitro inhibitory potency against the ChT-L activity in the β5 subunit, with over 80% inhibition at doses of 10 nM and above and little or no effect on the PGPH and T-L activities at doses up to 100 nM. Carfilzomib decreases the viability of ANBL-6, RPMI 8226 cells, U266 and KAS-6/1 cells with an IC₅₀ less than 5 nM. Carfilzomib overcome Dex resistance, in that MM1.R cells reveals an IC₅₀ of 15.2 nM, less than the value of 29.3 nM for parental MM1.S cells^[1]. Co-treatment with carfilzomib and HDACIs leads to synergistic induction of cell death in various mantle cell lymphoma lines and primary mantle cell lymphoma cells. Combined treatment with carfilzomib or ONX0912 with vorinostat in HF-4B and Granta cells sharply increases caspase activation, PARP cleavage, JNK activation, MnSOD2 induction, and DNA damage^[2].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

In Vivo

Note:
Please do not refer to only one article to determine the experimental conditions. It is recommended to determine the optimal experimental conditions (animal strain, age, dosage, frequency and cycle, detection time and indicators, etc.) through preliminary experiments before the formal experiment.

Carfilzomib (2.0 mg/kg, i.v.) in conbination with 70 mg/kg vorinostat virtually abrogates tumor growth in Granta-luciferace cell xenograft flank model. Combined treatment results in a pronounced reduction in bioluminescence compared to animals treated with single agents or controls with minimal toxicity^[2].

Carfilzomib exhibits high plasma clearance (195-319 mL/min?kg), short terminal half-life (5-20 min), and rapid and extensive tissue distribution in rats. Carfilzomib exposure (C_max and area under the curve) increases with dose. The high clearance is primarily mediated by extrahepatic metabolism via peptidase cleavage and epoxide hydrolysis, with approximately 26% and 31% of the total dose in urine and bile, respectively. Despite the high systemic clearance, strong proteasome inhibition was observed in blood and multiple tissues^[2].
Carfilzomib can be used in animal models to construct models of cardiotoxicity and hypertension.

1. Cardiotoxicity Model^[3]

Pathogenic mechanism

Carfilzomib inhibits AMPKα-mediated autophagy and the PI3K/Akt/eNOS axis, subsequently leading to cardiomyocyte damage and apoptosis, resulting in cardiotoxicity.

Specific modeling method

Mice: C57BL/6 • male • 12-week-old
Administration: 8 mg/kg • i.p. • once every two days for 6 days

Modeling success index

Molecular changes: Reduced phosphorylation of AMPKα, Raptor, LC3-II, PI3K, Akt, and eNOS.

Hemodynamics: Left ventricular FS% decreased, which means the contractile function weakened.

Antagonist products Metformin (HY-B0627)

2. Hypertension Model^[4]

Pathogenic mechanism

Carfilzomib induces AMPKα dephosphorylation, leading to dysregulation of renal collecting duct ion channel homeostasis, thereby dysregulating water ion reabsorption and increasing cardiac preload to induce hypertension.

Specific modeling method

Mice: C57BL/6 • male • 12-14 weeks old
Administration: 8 mg/kg • i.p. • once every 2 days for 7 days

Modeling success index

Molecular changes: Inducible nitric oxide synthase (iNOS) and microtubule-associated protein 1A/1B light chain 3B (LC3-B) expression increased, and AMPKα phosphorylation decreased. Collecting duct ion channel epithelial Na⁺ channel (ENaC), Na⁺/K⁺/ATPase, and urea transporter 1 (UTA-1) mRNA levels increased.

Behavioral observations: Inflammation occurred in the perirenal adipose tissue of mice.

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Ensayo clínico

Peso molecular

719.91

Fòrmula

C₄₀H₅₇N₅O₇

No. CAS

868540-17-4

Appearance

Solid

Color

White to off-white

SMILES

C[C@@]1(C([C@H](CC(C)C)NC([C@@H](NC([C@H](CC(C)C)NC([C@@H](NC(CN2CCOCC2)=O)CCC3=CC=CC=C3)=O)=O)CC4=CC=CC=C4)=O)=O)OC1

Envío

Room temperature in continental US; may vary elsewhere.

Almacenamiento

Powder	-20°C	3 years
	4°C	2 years

*The compound is unstable in solutions, freshly prepared is recommended.

Solvente y solubilidad

In Vitro:

DMSO : 125 mg/mL (173.63 mM; Need ultrasonic; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)

Preparing
Stock Solutions

Concentration Solvent Mass	1 mg	5 mg	10 mg

1 mM	1.3891 mL	6.9453 mL	13.8906 mL
5 mM	0.2778 mL	1.3891 mL	2.7781 mL
10 mM	0.1389 mL	0.6945 mL	1.3891 mL

View the Complete Stock Solution Preparation Table

* Please refer to the solubility information to select the appropriate solvent. The compound is unstable in solutions, freshly prepared is recommended.

Select the appropriate dissolution method based on your experimental animal and administration route.

For the following dissolution methods, please ensure to first prepare a clear stock solution using an In Vitro approach and then sequentially add co-solvents:
To ensure reliable experimental results, the clarified stock solution can be appropriately stored based on storage conditions. As for the working solution for in vivo experiments, it is recommended to prepare freshly and use it on the same day.
The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.

Protocol 1

Add each solvent one by one: 10% DMSO 40% PEG300 5% Tween-80 45% Saline
Solubility: 2.5 mg/mL (3.47 mM); Suspended solution; Need ultrasonic

This protocol yields a suspended solution of 2.5 mg/mL. Suspended solution can be used for oral and intraperitoneal injection.
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 400 μL PEG300, and mix evenly; then add 50 μL Tween-80 and mix evenly; then add 450 μL Saline to adjust the volume to 1 mL.
Preparation of Saline: Dissolve 0.9 g sodium chloride in ddH₂O and dilute to 100 mL to obtain a clear Saline solution.
Protocol 2

Add each solvent one by one: 10% DMSO 90% Corn Oil
Solubility: ≥ 2.5 mg/mL (3.47 mM); Clear solution

This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown). If the continuous dosing period exceeds half a month, please choose this protocol carefully.
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 900 μL Corn oil, and mix evenly.
Protocol 3

Add each solvent one by one: 5% DMSO 40% PEG300 5% Tween-80 50% Saline
Solubility: 2.5 mg/mL (3.47 mM); Suspended solution; Need ultrasonic

Pureza y Documentación

Purity: 99.96%

Ficha de datos (288 KB) SDS (396 KB)

COA (251 KB) RP-HPLC (335 KB)

Instrucciones de manejo (2659 KB)

Referencias

[1]. Kawada T, Iwai K. In vivo and in vitro metabolism of dihydrocapsaicin, a pungent principle of hot pepper [Capsicum annuum], in rats[J]. Agricultural and Biological Chemistry (Japan), 1985, 49(2).

[2]. Yang J, et al. Pharmacokinetics, pharmacodynamics, metabolism, distribution, and excretion of carfilzomib in rats. Drug Metab Dispos. 2011 Oct;39(10):1873-82. [Content Brief]

[3]. Efentakis P, et al. Molecular mechanisms of carfilzomib-induced cardiotoxicity in mice and the emerging cardioprotective role of metformin. Blood. 2019 Feb 14;133(7):710-723. [Content Brief]

[4]. Panagiotis Efentakis, et al. Carfilzomib-Induced Hypertension Is Mediated By Ion Channel Dysregulation in the Kidneys; The Potent Role of AMP-Activated Kinase α. Blood, Volume 136, Supplement 1, 2020, Pages 34-35, ISSN 0006-4971.

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Carfilzomib [868540-17-4]

Referencia HY-10455-5mg

Contact local distributor :

Marca : MedChemExpress

Contact local distributor :

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