HY-10455-5mg | Carfilzomib [868540-17-4] Clinisciences

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]
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]
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	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	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	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	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	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	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

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].

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.

Calculadora de molaridad
Calculadora de dilución

Mass (g) = Concentration (mol/L) × Volume (L) × Molecular Weight (g/mol)

Concentration _(start) × Volume _(start) = Concentration _(final) × Volume _(final)

This equation is commonly abbreviated as: C₁V₁ = C₂V₂

Concentration _(start)

Volume _(start)

Concentration _(final)

Volume _(final)

In Vivo:

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

In Vivo Dissolution Calculator

Please enter the basic information of animal experiments:

Dosage

mg/kg

Animal weight
(per animal)

Dosing volume
(per animal)

μL

Number of animals

Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.

Please enter your animal formula composition:

DMSO +

Tween-80 +

Saline

Recommended: Keep the proportion of DMSO in working solution below 2% if your animal is weak.

The co-solvents required include: DMSO, . All of co-solvents are available by MedChemExpress (MCE). , Tween 80. All of co-solvents are available by MedChemExpress (MCE).

Calculation results:

Working solution concentration: mg/mL

Method for preparing stock solution: mg drug dissolved in μL DMSO (Stock solution concentration: mg/mL).

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

The concentration of the stock solution you require exceeds the measured solubility. The following solution is for reference only. If necessary, please contact MedChemExpress (MCE).

Method for preparing in vivo working solution for animal experiments: Take μL DMSO stock solution, add μL . μL , mix evenly, next add μL Tween 80, mix evenly, then add μL Saline.

If the continuous dosing period exceeds half a month, please choose this protocol carefully.

Please ensure that the stock solution in the first step is dissolved to a clear state, and add co-solvents in sequence. You can use ultrasonic heating (ultrasonic cleaner, recommended frequency 20-40 kHz), vortexing, etc. to assist dissolution.

Pureza y Documentación

Purity: 99.98%

Select Batch:

SDS (393 KB)

COA (251 KB) HNMR (298 KB) RP-HPLC (242 KB) LCMS (87 KB)

Instrucciones de manejo (2659 KB)

Referencias

[1]. Kuhn DJ, et al. Potent activity of carfilzomib, a novel, irreversible inhibitor of the ubiquitin-proteasome pathway, against preclinical models of multiple myeloma. Blood. 2007 Nov 1;110(9):3281-90. [Content Brief]

[2]. Dasmahapatra G, et al. Carfilzomib interacts synergistically with histone deacetylase inhibitors in mantle cell lymphoma cells in vitro and in vivo. Mol Cancer Ther. 2011 Sep;10(9):1686-97. [Content Brief]

Ensayo celular ^[1]	WST-1 is used to determine the effects of proteasome inhibitors on cell proliferation according to the manufacturer's protocol. The inhibition of proliferation is calculated in relation to parallel control cells that receive vehicle alone and tabulated in KaleidaGraph 3.0.1 or Excel 2000. A linear spline function is used to interpolate the median inhibitory concentration (IC₅₀) using XLfit 4 software. The degree of resistance (DOR) is calculated using the formula: DOR=IC₅₀(resistant cells)/IC₅₀(sensitive cells). MCE no ha confirmado la precisión de estos métodos independientemente. Son solo para referencia.
Administraciòn de animales ^[2]	Animal studies are performed utilizing Beige-nude-XID mice. 10×10⁶ Granta514 cells are pelleted, washed twice with 1X PBS, injected subcutaneously into the right flank. Once the tumors are visible, 5 to 6 mice are treated with carfilzomib±vorinostat and progress of tumor growth or regression is monitored. Stock vorinostat and carfilzomib is dissolved in DMSO and 10% sulfobutylether betacyclodextrin in 10 mM citrate buffer pH respectively. They are stored in −80°C in small aliquots and diluted before injection. MCE no ha confirmado la precisión de estos métodos independientemente. Son solo para referencia.
Referencias	[1]. Kuhn DJ, et al. Potent activity of carfilzomib, a novel, irreversible inhibitor of the ubiquitin-proteasome pathway, against preclinical models of multiple myeloma. Blood. 2007 Nov 1;110(9):3281-90. [Content Brief] [2]. Dasmahapatra G, et al. Carfilzomib interacts synergistically with histone deacetylase inhibitors in mantle cell lymphoma cells in vitro and in vivo. Mol Cancer Ther. 2011 Sep;10(9):1686-97. [Content Brief]

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.

Optional Solvent	Concentration Solvent Mass	1 mg	5 mg	10 mg	25 mg

DMSO	1 mM	1.3891 mL	6.9453 mL	13.8906 mL	34.7266 mL
	5 mM	0.2778 mL	1.3891 mL	2.7781 mL	6.9453 mL
	10 mM	0.1389 mL	0.6945 mL	1.3891 mL	3.4727 mL
	15 mM	0.0926 mL	0.4630 mL	0.9260 mL	2.3151 mL
	20 mM	0.0695 mL	0.3473 mL	0.6945 mL	1.7363 mL
	25 mM	0.0556 mL	0.2778 mL	0.5556 mL	1.3891 mL
	30 mM	0.0463 mL	0.2315 mL	0.4630 mL	1.1576 mL
	40 mM	0.0347 mL	0.1736 mL	0.3473 mL	0.8682 mL
	50 mM	0.0278 mL	0.1389 mL	0.2778 mL	0.6945 mL
	60 mM	0.0232 mL	0.1158 mL	0.2315 mL	0.5788 mL
	80 mM	0.0174 mL	0.0868 mL	0.1736 mL	0.4341 mL
	100 mM	0.0139 mL	0.0695 mL	0.1389 mL	0.3473 mL

Carfilzomib Related Classifications

Metabolic Enzyme/Protease Autophagy Apoptosis
Proteasome Autophagy Apoptosis

Carfilzomib [868540-17-4]

Referencia HY-10455-5mg

Contact local distributor :

Marca : MedChemExpress

Contact local distributor :

Other Forms of Carfilzomib:

Calculadora de molaridad

Calculadora de dilución

Complete Stock Solution Preparation Table

Carfilzomib Related Classifications

Keywords:

Usted podría estar interesado también en los siguientes productos:

Carfilzomib [868540-17-4]

Referencia HY-10455-5mg

Contact local distributor :

Marca : MedChemExpress

Contact local distributor :

Other Forms of Carfilzomib:

Carfilzomib Related Antibodies

Calculadora de molaridad

Calculadora de dilución

Complete Stock Solution Preparation Table

Carfilzomib Related Classifications

Keywords:

Usted podría estar interesado también en los siguientes productos: