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Nutlin-3 p53-MDM2 Inhibitor

Name: Nutlin-3
Brand: Selleck Chemicals
SKU: S1061
Rating: 5 (109 reviews)

Cat. No.: S1061

Nutlin-3 is a potent and selective Mdm2 (RING finger-dependent ubiquitin protein ligase for itself and p53) antagonist with IC50 of 90 nM in a cell-free assay; stabilizes p73 in p53-deficient cells.

Nutlin-3 MDM2/MDMX antagonist Chemical Structure

Estructura química

Peso molecular: 581.5

Saltar a

Control de calidad (Quality Control)

Lote: Pureza: 99.59%

99.59

Productos que se suelen utilizar junto con Nutlin-3

Tozasertib (VX-680, MK-0457)

Combined with Tozasertib, this compound selectively kills p53-compromised cells and inhibits the proliferation of cells expressing wild-type p53.

Dianas relacionadas	Bcl-2 Caspase PD-1/PD-L1 Ferroptosis p53 Apoptosis related Synthetic Lethality STAT TNF-alpha Ras
Otros MDM2/MDMX Inhibidores	RG-7112 Nutlin-3a Brigimadlin Idasanutlin (RG7388) SAR405838 NSC 207895 NVP-CGM097 Siremadlin (HDM201) Nutlin-3b YH239-EE

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
SMMC-7721	Function Assay	10 μM	36 h	DMSO	down-regulates the protein expression level of phospho-Ser392-p53	24286312
HuH-7	Apoptosis Assay	20 μM	48 h	DMSO	induces apoptosis	24286312
SMMC-7721	Apoptosis Assay	20 μM	48 h	DMSO	induces apoptosis	24286312
HuH-7	Cell Viability Assay	1.25-20 μM	24/48/72 h	DMSO	inhibits cell proliferation dose and time dependently	24286312
SMMC-7721	Cell Viability Assay	1.25-20 μM	24/48/72 h	DMSO	inhibits cell proliferation dose and time dependently	24286312
RKO	Function Assay	20 μM	24 h		induces HO-1 expression at the level of transcription	24366007
U2OS	Function Assay	20 μM	24 h		induces HO-1 expression at the level of transcription	24366007
RKO	Function Assay	20 μM	24 h		increases the levels of the HO-1 protein as well as the p53 protein	24366007
U2OS	Function Assay	20 μM	24 h		increases the levels of the HO-1 protein as well as the p53 protein	24366007
MOLM	Function Assay	10 μM	24 h		upregulates the SOCS-1 expression	24473562
OCI	Function Assay	10 μM	24 h		upregulates the SOCS-1 expression	24473562
BeWo	Apoptosis Assay	30 µM	24 h		increases apoptosis	24498154
BeWo	Function Assay	30 µM	24 h		increases p53, Mdm2, p21 and Puma at the protein level	24498154
MOML13	Function Assay	10μM	2/4 h		increases the level of p53	24659749
AML3	Function Assay	10μM	2/4 h		increases the level of p53	24659749
AML2	Function Assay	10μM	2/4 h		increases the level of p53	24659749
MOML13	Apoptosis Assay	2/10 μM	24/48 h		induces apoptosis	24659749
AML2	Apoptosis Assay	2/10 μM	24/48 h		induces apoptosis	24659749
U2OS	Function Assay	20 μM	24 h		increases the mRNA levels of BCL2A1, BCLXL andBCLW	24867259
Hep3B	Apoptosis Assay				induces apoptosis	24884809
Huh-7	Apoptosis Assay				induces apoptosis	24884809
SMMC7721	Apoptosis Assay				induces apoptosis	24884809
HepG2	Apoptosis Assay				induces apoptosis	24884809
Hep3B	Growth Inhibition Assay		72 h	DMSO	IC50=20.18 ± 1.84 μM	24884809
Huh-7	Growth Inhibition Assay		72 h	DMSO	IC50=33.96 ± 3.9 μM	24884809
SMMC7721/Ac	Growth Inhibition Assay		72 h	DMSO	IC50=55.21 ± 5.03 μM	24884809
SMMC7721	Growth Inhibition Assay		72 h	DMSO	IC50=31.28 ± 4.2 μM	24884809
HepG2/As	Growth Inhibition Assay		72 h	DMSO	IC50=68.13 ± 9.6 μM	24884809
HepG2	Growth Inhibition Assay		72 h	DMSO	IC50=35.86 ± 2.9 μM	24884809
MOLM-13	Function Assay	6 μM	6 h	DMSO	enhances the acetylation of histone H2B and heat shock proteins Hsp27 and Hsp90	24885082
MOLM-13	Function Assay	6 μM	0-8 h	DMSO	increases the levels of p53, MDM2, p21 and acetylated p53	24885082
115	Function Assay	5 μM	48 h	DMSO	induces p53-dependent senescence	25067787
A498	Function Assay	5 μM	48 h	DMSO	induces p53-dependent senescence	25067787
Caki-2	Function Assay	5 μM	48 h	DMSO	induces p53-dependent senescence	25067787
ACHN	Function Assay	5 μM	48 h	DMSO	induces p53-dependent senescence	25067787
115	Growth Inhibition Assay	5 μM	48 h	DMSO	induces cell cycle arrest	25067787
A498	Growth Inhibition Assay	5 μM	48 h	DMSO	induces cell cycle arrest	25067787
Caki-2	Growth Inhibition Assay	5 μM	48 h	DMSO	induces cell cycle arrest	25067787
ACHN	Growth Inhibition Assay	5 μM	48 h	DMSO	induces cell cycle arrest	25067787
115	Function Assay	0.5/1/5 μM	48 h	DMSO	leads to increased expression of p53 and some p53 target genes: MDM2, and p21	25067787
A498	Function Assay	0.5/1/5 μM	48 h	DMSO	leads to increased expression of p53 and some p53 target genes: MDM2, and p21	25067787
Caki-2	Function Assay	0.5/1/5 μM	48 h	DMSO	leads to increased expression of p53 and some p53 target genes: MDM2, and p21	25067787
ACHN	Function Assay	0.5/1/5 μM	48 h	DMSO	leads to increased expression of p53 and some p53 target genes: MDM2, and p21	25067787
117	Cell Viability Assay	0.5-10 μM	0-6 d	DMSO	inhibits proliferation in a dose-dependent manner	25067787
115	Cell Viability Assay	0.5-10 μM	0-6 d	DMSO	inhibits proliferation in a dose-dependent manner	25067787
A498	Cell Viability Assay	0.5-10 μM	0-6 d	DMSO	inhibits proliferation in a dose-dependent manner	25067787
Caki-2	Cell Viability Assay	0.5-10 μM	0-6 d	DMSO	inhibits proliferation in a dose-dependent manner	25067787
ACHN	Cell Viability Assay	0.5-10 μM	0-6 d	DMSO	inhibits proliferation in a dose-dependent manner	25067787
MCF7	Function Assay	2.5 µM	48 h	DMSO	decreases the homologous DSB repair frequencies	25085902
MCF7	Cell Viability Assay	2.5 µM	5 d	DMSO	sensitizes MCF7 to PARP inhibition	25085902
RAW 264.7	Function Assay	10 μM	30 min		inhibits LPS-induced NO production	25172547
RAW 264.7	Function Assay	10 μM	30 min		reduces the LPS-augmented the NF-κB luciferase reporter gene activity	25172547
RAW 264.7	Function Assay	10 μM	30 min		prevents the p53 reduction in response to LPS	25172547
SUM102PT	Function Assay	10 μM	24 h	DMSO	inhibits TGF-β3-induced EPHB2 mRNA and protein expression	25257729
SK-BR-7	Function Assay	10 μM	24 h	DMSO	inhibits TGF-β3-induced EPHB2 mRNA and protein expression	25257729
MCF-10CA1a	Function Assay	10 μM	24 h	DMSO	inhibits TGF-β3-induced EPHB2 mRNA and protein expression	25257729
MCF-10CA1a	Function Assay	10 μM	24 h	DMSO	decreases the TGF-β3-induced mRNA levels ofMMP2, MMP9, and integrin β 3	25257729
MCF-10A1	Function Assay	10 μM	24/48 h	DMSO	inhibits migration of normal breast epithelial	25257729
MCF-10CA1a	Function Assay	10 μM	48 h	DMSO	inhibits basal invasion and reduced TGF-β3-induced invasion to basal levels	25257729
HCT116	Function Assay	10 µM	24 h		causes a p53-dependent tetraploid G1-arrest in diploid HCT116 clones D3 and D8	25380055
A2780	Function Assay	10 μM	21h	DMSO	decreases the FoxM1 levels	25426548
NCI-H23	Function Assay	10 μM	21h	DMSO	decreases the FoxM1 levels	25426548
A2780	Function Assay	10 μM	21h	DMSO	increases p53 protein levels	25426548
NCI-H23	Function Assay	10 μM	21h	DMSO	increases p53 protein levels	25426548
OVCAR10	Function Assay	10 μM	21h	DMSO	increases p53 protein levels	25426548
MCF-7	Function Assay	10 μM	0-24 h		induces p53 and p21/Cip1	25482373
SMMC-7721	Function Assay	10 μM	36 h	DMSO	causes the ectopic expression of IFI16	25544361
SMMC-7721	Function Assay	10 μM	48 h	DMSO	increases the expression level of IFNB1 mRNA	25544361
SMMC-7721	Function Assay	10 μM	48 h	DMSO	induces the chromatin-bound protein IFI16 to partially localize in the cytoplasm	25544361
SMMC-7721	Function Assay	10 μM	48 h	DMSO	causes DNA DSB damage	25544361
DU4475	Function Assay	5/10/20 μM	24 h		downregulates Toca-1 dose dependently	25547174
MCF-7	Function Assay	10 μM		DMSO	inhibits cyclin D1 and Dicer	25702703
C2C12	Growth Inhibition Assay	10 μM	24/48/72 h	DMSO	inhibits cells proliferation and differentiation	25871794
L6	Growth Inhibition Assay	10 μM	24/48/72 h	DMSO	inhibits cells proliferation and differentiation	25871794
CRL-5908	Growth Inhibition Assay		24 h		IC50=38.71 ± 2.43 μM	26125230
A549-920	Growth Inhibition Assay		24 h		IC50=33.85 ± 4.84 μM	26125230
A549-NTC	Growth Inhibition Assay		24 h		IC50=19.42 ± 1.96 μM	26125230
A549	Growth Inhibition Assay		24 h		IC50=17.68 ± 4.52 μM	26125230
C666-1	Apoptosis Assay	10 µM	48/72 h	DMSO	sensitizes C666-1 cells to cisplatin-induced apoptosis	26252575
C666-1	Function Assay	10 µM	24 h	DMSO	activates the p53 pathway, upregulating p53, p21 and Mdm2	26252575
C666-1	Cell Viability Assay	10 µM	48 h	DMSO	sensitizes C666-1 cells to the cytotoxic effect of cisplatin	26252575
C666-1	Growth Inhibition Assay				IC50=19.95±8.93 μM	26252575
NP460	Growth Inhibition Assay				IC50=22.85±1.18 μM	26252575
NP69	Growth Inhibition Assay				IC50=31.69±2.54 μM	26252575
MCF7	Growth Inhibition Assay	5 μM	48 h		blocks 27-OHC-induced cell proliferation comparable to that of basal levels	26350565
HuH-7	Function Assay	10 μM	36 h	DMSO	down-regulates the protein expression level of phospho-Ser392-p53	24286312
AT2	Function Assay	5/10 μM			leads to a substantial accumulation of the p53 protein as well as the expression of its direct targets p21, MDM2 and the pro-apoptotic BAX and PUMA proteins	24240203
REH	Function Assay	5/10 μM			leads to a substantial accumulation of the p53 protein as well as the expression of its direct targets p21, MDM2 and the pro-apoptotic BAX and PUMA proteins	24240203
UoCB6	Function Assay	5/10 μM			leads to a substantial accumulation of the p53 protein as well as the expression of its direct targets p21, MDM2 and the pro-apoptotic BAX and PUMA proteins	24240203
AT2	Cell Viability Assay	0-25 μM			inhibits cell viability dose dependently	24240203
REH	Cell Viability Assay	0-25 μM			inhibits cell viability dose dependently	24240203
UoCB6	Cell Viability Assay	0-25 μM			inhibits cell viability dose dependently	24240203
A2780	Function Assay	5/10/20 μM	24 h		upregulates p53, MDM2, p21 and DR5 protein levels dose dependently	24136147
H460	Function Assay	5/10/20 μM	24 h		upregulates p53, MDM2, p21 and DR5 protein levels dose dependently	24136147
Lovo	Function Assay	5/10/20 μM	24 h		upregulates p53, MDM2, p21 and DR5 protein levels dose dependently	24136147
A2780	Apoptosis Assay	5/10/20 μM	24 h		enhances apoptosis induction by D269H/E195R over rhTRAIL	24136147
H460	Apoptosis Assay	5/10/20 μM	24 h		enhances apoptosis induction by D269H/E195R over rhTRAIL	24136147
Lovo	Apoptosis Assay	5/10/20 μM	24 h		enhances apoptosis induction by D269H/E195R over rhTRAIL	24136147
U87MG	Function assay		10 mins		Binding affinity to MDM2 in human U87MG cells assessed as inhibition of MDM2/p53 protein interaction after 10 mins by quantitative sandwich immuno assay, IC50 = 0.1045 μM.	27050782
U87MG	Antiproliferative assay		48 hrs		Antiproliferative activity against human U87MG cells expressing wild type p53 after 48 hrs by MTS assay, IC50 = 6.5 μM.	27050782
U343MG	Antiproliferative assay		48 hrs		Antiproliferative activity against human U343MG cells expressing wild type p53 after 48 hrs by MTS assay, IC50 = 12.6 μM.	27050782
SW620	Cytotoxicity assay		72 hrs		Cytotoxicity against human SW620 cells after 72 hrs by SRB assay, IC50 = 0.38 μM.	ChEMBL
A549	Cytotoxicity assay		72 hrs		Cytotoxicity against human A549 cells after 72 hrs by SRB assay, IC50 = 0.41 μM.	ChEMBL
SJSA1	Cytotoxicity assay		72 hrs		Cytotoxicity against human SJSA1 cells after 72 hrs by SRB assay, IC50 = 1.81 μM.	ChEMBL
HCT116	Cytotoxicity assay		72 hrs		Cytotoxicity against human HCT116 cells after 72 hrs by SRB assay, IC50 = 4.63 μM.	ChEMBL
PC3	Cytotoxicity assay		72 hrs		Cytotoxicity against human PC3 cells after 72 hrs by SRB assay, IC50 = 6.37 μM.	ChEMBL
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Información química, almacenamiento y estabilidad (Chemical Information, Storage & Stability)

Peso molecular	581.5	Fórmula	C₃₀H₃₀Cl₂N₄O₄	Almacenamiento (Desde la fecha de recepción)	3 años-20°Cpolvo
Nº CAS	890090-75-2	Descargar SDF		Almacenamiento de soluciones madre	1 año-80°Cen disolvente 1 mes-20°Cen disolvente
Sinónimos	N/A			Smiles	CC(C)OC1=C(C=CC(=C1)OC)C2=NC(C(N2C(=O)N3CCNC(=O)C3)C4=CC=C(C=C4)Cl)C5=CC=C(C=C5)Cl

Solubilidad (Solubility)

In vitro
Lote:

DMSO : 100 mg/mL (171.96 mM)
(El DMSO contaminado con humedad puede reducir la solubilidad. Usar DMSO fresco y anhidro.)

Ethanol : 100 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.
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.
Clear solution	5%DMSO 1 40%PEG300 2 5%Tween80 3 50%ddH2O Validado por los laboratorios Selleck. Si necesita ajustes en esta formulación, contacte con nuestro equipo de ventas para pruebas personalizadas.	5.000mg/ml (8.60mM)	Taking the 1 mL working solution as an example, add 50 μL of 100 mg/ml clarified DMSO stock solution to 400 μL of PEG300, mix evenly to clarify it; add 50 μL of Tween80 to the above system, mix evenly to make it clear; then continue to add 500 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.

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	MDM2 (Cell-free assay) 180 nM
In vitro	Nutlin-3 potently inhibits the MDM2-p53 interaction, leading to the activation of the p53 pathway. This compound treatment induces the expression of MDM2 and p21, and displays potent antiproliferative activity with IC50 of ~1.5 μM, only in cells with wild-type p53 such as HCT116, RKO and SJSA-1, but not in the mutant p53 cell lines SW480 and MDA-MB-435. In SJSA-1 cells, this compound treatment at 10 μM for 48 hours significantly induces caspase-dependent cell apoptosis by ~45%. Although it also inhibits the growth and viability of human skin (1043SK) and mouse embryo (NIH/3T3) with IC50 of 2.2 μM and 1.3 μM, respectively, cells remain viable 1 week post-treatment even at 10 μM of this chemical, in contrast with the SJSA-1 cells with viability lost at 3 μM of this chemical treatment. It does not induce the phosphorylation of p53 on key serine residues and reveals no difference in their sequence-specific DNA binding and ability to transactivate p53 target genes compared with phosphorylated p53 induced by the genotoxic drugs doxorubicin, demonstrating that phosphorylation of p53 on key serines is dispensable for transcriptional activation and apoptosis. Although binding less efficiently to MDMX than to MDM2, this compound can block the MDMX–p53 interaction and induce the p53 pathway in retinoblastoma cells (Weri1) with IC50 of 0.7 μM. This chemical at 30 μM also disrupts endogenous p73-HDM2 interaction and enhances the stability and proapoptotic activities of p73, leading to the dose-dependent cell growth inhibition and apoptosis induction in cells without wild-type p53.
Ensayo de quinasa	Estudio Biacore
Ensayo de quinasa	El ensayo de competición se realiza en un Biacore S51. Se utiliza un chip de sensor de la serie S CM5 para la inmovilización de un anticuerpo PentaHis para la captura de la p53 con etiqueta His. El nivel de captura es de ~200 unidades de respuesta (1 unidad de respuesta corresponde a 1 pg de proteína por mm²). La concentración de proteína MDM2 se mantiene constante en 300 nM. Nutlin-3 se disuelve en DMSO a 10 mM y se diluye aún más para hacer una serie de concentraciones de este compuesto en cada muestra de prueba de MDM2. El ensayo se realiza a 25 °C en tampón de ejecución (10 mM Hepes, 0,15 M NaCl, 2 % DMSO). La unión MDM2-p53 en presencia de este químico se calcula como un porcentaje de la unión en ausencia del mismo y se calcula la IC50.
In vivo	Oral administration of Nutlin-3 at 200 mg/kg twice daily for 3 weeks significantly inhibits the tumor growth of SJAS-1 xenografts by 90%, comparable with the effect of doxorubicin treatment with 81% inhibition of tumor growth.
Referencias	[1] https://pubmed.ncbi.nlm.nih.gov/14704432/ [2] https://pubmed.ncbi.nlm.nih.gov/15471885/ [3] https://pubmed.ncbi.nlm.nih.gov/17080083/ [4] https://pubmed.ncbi.nlm.nih.gov/17700533/ [5] http://eprints.lib.hokudai.ac.jp/dspace/bitstream/2115/54893/1/Masaki_Miyazaki.pdf

Aplicaciones (Applications)

Métodos	Biomarcadores	PMID
Western blot	MDM2 / p53 / ALKBH2 / p21 / PUMA RRM1 / RRM2 / p53R2 / p21 / p53 / pS6 / S6	23258843
Immunofluorescence	Lamin A / Lamin C / p16 / H3K9me3 Merlin / cyclin D1 / p53 / MDM2 p53	30728349
Growth inhibition assay	Cell viability	29286113

Preguntas frecuentes (Frequently Asked Questions)

Pregunta 1:
Is this a racemic mixture of its enantiomers or just the Nutlin-3a enantiomer?

Respuesta:
It is a racemate.

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):