Nutlin-3

For research use only.

Catalog No.S1061

54 publications

Nutlin-3 Chemical Structure

CAS No. 890090-75-2

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.

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Selleck's Nutlin-3 has been cited by 54 publications

Purity & Quality Control

Choose Selective Mdm2 Inhibitors

Biological Activity

Description 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.
Targets
Mdm2 [5]
(Cell-free assay)
180 nM
In vitro

Nutlin-3 potently inhibits the MDM2-p53 interaction, leading to the activation of the p53 pathway. Nutlin-3 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, Nutlin-3 treatment at 10 μM for 48 hours significantly induces caspase-dependent cell apoptosis by ~45%. Although Nutlin-3 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 Nutlin-3, in contrast with the SJSA-1 cells with viability lost at 3 μM of Nutlin-3 treatment. [1] Nutlin-3 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 and etoposide, demonstrating that phosphorylation of p53 on key serines is dispensable for transcriptional activation and apoptosis. [2] Although binding less efficiently to MDMX than to MDM2, Nutlin-3 can block the MDMX–p53 interaction and induce the p53 pathway in retinoblastoma cells (Weri1) with IC50 of 0.7 μM. [3] Nutlin-3 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. [4]

Cell Data
Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
SMMC-7721  NGezNnpHfW6ldHnvckBCe3OjeR?= MmPuNVAh|ryP MkXaN|YhcA>? M1vNZmROW09? NG\6eHZld3ewLYLl[5Vt[XSnczD0bIUheHKxdHXpckBmgHC{ZYPzbY9vKGyndnXsJI9nKHCqb4PwbI8uW2W{M{myMZA2Ow>? M4rtWVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ2Mki2N|EzLz5{NEK4OlMyOjxxYU6=
HuH-7 MoDmRZBweHSxc3nzJGF{e2G7 NWrKfpRmOjBizszN MXu0PEBp NHP6fmFFVVOR M4H6XIlv\HWlZYOgZZBweHSxc3nz MYe8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPDJ6NkOxNkc,OjR{OE[zNVI9N2F-
SMMC-7721  M4n6O2Fxd3C2b4Ppd{BCe3OjeR?= M1fFUlIxKM7:TR?= MYq0PEBp NUiyc45nTE2VTx?= MVPpcoR2[2W|IHHwc5B1d3Orcx?= NW\KW4dsRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkSyPFY{OTJpPkK0Nlg3OzF{PD;hQi=>
HuH-7 M1HpRWNmdGxiVnnhZoltcXS7IFHzd4F6 MYexMlI2NTJyIN88US=> MWiyOE81QC95MjDo NV6yfm12TE2VTx?= M17qSIlvcGmkaYTzJINmdGxicILvcIln\XKjdHnvckBld3OnIHHu[EB1cW2nIHTldIVv\GWwdHz5 MnPaQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjR{OE[zNVIoRjJ2Mki2N|EzRC:jPh?=
SMMC-7721  MleyR4VtdCCYaXHibYxqfHliQYPzZZk> MYmxMlI2NTJyIN88US=> MoXxNlQwPDhxN{KgbC=> NYG5b297TE2VTx?= NUHyWIEzcW6qaXLpeJMh[2WubDDwdo9tcW[ncnH0bY9vKGSxc3WgZY5lKHSrbXWg[IVx\W6mZX70cJk> NHzkR2w9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NEK4OlMyOid-MkSyPFY{OTJ:L3G+
RKO NYjSeoZ2TnWwY4Tpc44hSXO|YYm= MX6yNEDPxE1? MX:yOEBp NVrCRW15cW6mdXPld{BJVy1zIHX4dJJme3Orb36gZZQhfGinIHzleoVtKG:oIITyZY5{[3KrcITpc44> Ml34QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjR|Nk[wNFcoRjJ2M{[2NFA4RC:jPh?=
U2OS  M3vsSmZ2dmO2aX;uJGF{e2G7 M4nPXlIxKM7:TR?= NUnscVlTOjRiaB?= NETvPWRqdmS3Y3XzJGhQNTFiZYjwdoV{e2mxbjDheEB1cGVibHX2[Ywhd2ZidILhcpNkemmydHnvci=> NEfFT5Y9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NEO2OlAxPyd-MkSzOlYxODd:L3G+
RKO MoHpSpVv[3Srb36gRZN{[Xl? NIPyWWozOCEQvF2= MmTDNlQhcA>? M2fzUIlv[3KnYYPld{B1cGVibHX2[Yx{KG:oIITo[UBJVy1zIIDyc5RmcW5iYYOge4VtdCCjczD0bIUheDV|IIDyc5RmcW5? M{LTcFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ2M{[2NFA4Lz5{NEO2OlAxPzxxYU6=
U2OS  MkjBSpVv[3Srb36gRZN{[Xl? M4DrVFIxKM7:TR?= NGraUYczPCCq MoHsbY5kemWjc3XzJJRp\SCuZY\lcJMhd2ZidHjlJGhQNTFicILveIVqdiCjczD3[YxtKGG|IITo[UBxPTNicILveIVqdg>? MoXPQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjR|Nk[wNFcoRjJ2M{[2NFA4RC:jPh?=
MOLM M3XvUWZ2dmO2aX;uJGF{e2G7 MlnYNVAh|ryP MnWyNlQhcA>? MV71dJJm\3WuYYTld{B1cGViU1;DV{0yKGW6cILld5Nqd25? MkflQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjR2N{O1OlIoRjJ2NEezOVYzRC:jPh?=
OCI NHmxVIRHfW6ldHnvckBCe3OjeR?= MYCxNEDPxE1? NWjwS5hiOjRiaB?= NVXNR3I1fXC{ZXf1cIF1\XNidHjlJHNQS1NvMTDlfJBz\XO|aX;u NEXUb3Q9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NES3N|U3Oid-MkS0O|M2PjJ:L3G+
BeWo Moe1RZBweHSxc3nzJGF{e2G7 MV2zNEDDvU1? M4nyVVI1KGh? MWDpcoNz\WG|ZYOgZZBweHSxc3nz M1;C[lxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ2NEm4NVU1Lz5{NES5PFE2PDxxYU6=
BeWo NYT3OFdpTnWwY4Tpc44hSXO|YYm= Mn\ZN|AhyrWP NUX5ZXN1OjRiaB?= Mm\jbY5kemWjc3XzJJA2OyxiTXTtNkwheDJzIHHu[EBRfW2jIHH0JJRp\SCycn;0[YlvKGyndnXs M{G1fVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ2NEm4NVU1Lz5{NES5PFE2PDxxYU6=
MOML13 M{fDZmZ2dmO2aX;uJGF{e2G7 NFu0bYEyOM7:TR?= MWeyM|QhcA>? MlLUbY5kemWjc3XzJJRp\SCuZY\lcEBw\iCyNUO= MnrqQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjR4NUm3OFkoRjJ2NkW5O|Q6RC:jPh?=
AML3 M1jBUWZ2dmO2aX;uJGF{e2G7 MkPLNVDPxE1? M3PDT|IwPCCq NXWyb5RVcW6lcnXhd4V{KHSqZTDs[ZZmdCCxZjDwOVM> NFvSZVU9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NE[1PVc1QSd-MkS2OVk4PDl:L3G+
AML2 MnWxSpVv[3Srb36gRZN{[Xl? MYqxNO69VQ>? MnrPNk81KGh? MVrpcoNz\WG|ZYOgeIhmKGyndnXsJI9nKHB3Mx?= NHXLd5Q9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NE[1PVc1QSd-MkS2OVk4PDl:L3G+
MOML13 MXHBdI9xfG:|aYOgRZN{[Xl? NInOb3czNzFyIN88US=> MWKyOE81QCCq MVzpcoR2[2W|IHHwc5B1d3Orcx?= M3ThVVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ2NkW5O|Q6Lz5{NE[1PVc1QTxxYU6=
AML2 M{G5UGFxd3C2b4Ppd{BCe3OjeR?= Mnq5Nk8yOCEQvF2= MmjuNlQwPDhiaB?= NHvFc3dqdmS3Y3XzJIFxd3C2b4Ppdy=> NGPiXIo9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NE[1PVc1QSd-MkS2OVk4PDl:L3G+
U2OS  NYSyOGJOTnWwY4Tpc44hSXO|YYm= MkDiNlAh|ryP MmfjNlQhcA>? M{[4ZYlv[3KnYYPld{B1cGVibWLORUBt\X[nbIOgc4bDqEKFTELBNUwhSkOOWF|CpIFv\EKFTGe= NW\mZlZzRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkS4OlczPTlpPkK0PFY4OjV7PD;hQi=>
Hep3B NHjmRXRCeG:ydH;zbZMhSXO|YYm= NYXvR2VpcW6mdXPld{BieG:ydH;zbZM> MlLmQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjR6OES4NFkoRjJ2OEi0PFA6RC:jPh?=
Huh-7 MVXBdI9xfG:|aYOgRZN{[Xl? MkTZbY5lfWOnczDhdI9xfG:|aYO= Mo\VQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjR6OES4NFkoRjJ2OEi0PFA6RC:jPh?=
SMMC7721 MYDBdI9xfG:|aYOgRZN{[Xl? NVr1PWpRcW6mdXPld{BieG:ydH;zbZM> MUi8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPDh6NEiwPUc,OjR6OES4NFk9N2F-
HepG2 MXLBdI9xfG:|aYOgRZN{[Xl? NFKyZ4VqdmS3Y3XzJIFxd3C2b4Ppdy=> NHS4[289[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NEi4OFgxQSd-MkS4PFQ5ODl:L3G+
Hep3B M{G0O2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NIn4fWE4OiCq NY\Re5NwTE2VTx?= MmLRTWM2OD1{MD6xPEDDuSBzLki0JO69VQ>? MWm8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPDh6NEiwPUc,OjR6OES4NFk9N2F-
Huh-7 M2XIdWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NFzGUFE4OiCq MmKySG1UVw>? Mm\sTWM2OD1|Mz65OkDDuSB|Lkmg{txO Mkn1QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjR6OES4NFkoRjJ2OEi0PFA6RC:jPh?=
SMMC7721/Ac MXTHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MUi3NkBp NFqwcmNFVVOR M17uZmlEPTB;NUWuNlEhyrFiNT6wN{DPxE1? MoSxQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjR6OES4NFkoRjJ2OEi0PFA6RC:jPh?=
SMMC7721 MoTES5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M2H4OVczKGh? Ml;FSG1UVw>? M2L6VWlEPTB;M{GuNlghyrFiND6yJO69VQ>? MYi8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPDh6NEiwPUc,OjR6OES4NFk9N2F-
HepG2/As NFnYSIVIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NHS3O|M4OiCq M4\mUmROW09? NUHQUZdtUUN3ME22PE4yOyEEsTC5MlYh|ryP MV68ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPDh6NEiwPUc,OjR6OES4NFk9N2F-
HepG2 MoP4S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NYfKOolFPzJiaB?= M3;Tb2ROW09? MX;JR|UxRTN3Lki2JOKyKDJwOTFOwG0> NUL6Wlh5RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkS4PFQ5ODlpPkK0PFg1QDB7PD;hQi=>
MOLM-13 NIDNN5JHfW6ldHnvckBCe3OjeR?= NGrnOnc3yqEQvF2= MVG2JIg> NUGzbGJWTE2VTx?= NFXsT5hmdmijbnPld{B1cGViYXPleJlt[XSrb36gc4YhcGm|dH;u[UBJOkJiYX7kJIhm[XRic3jvZ4sheHKxdHXpcpMhUHOyMkegZY5lKEi|cEmw NWPOc49nRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkS4PFUxQDJpPkK0PFg2ODh{PD;hQi=>
MOLM-13 M1z5V2Z2dmO2aX;uJGF{e2G7 M4nNVVbDqM7:TR?= M3[yclAuQCCq MnXkSG1UVw>? NWrkU3VEcW6lcnXhd4V{KHSqZTDs[ZZmdHNib3[gdFU{NCCPRF2yMEBxOjFiYX7kJIFk\XS7bHH0[YQheDV| M1:2SlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ2OEi1NFgzLz5{NEi4OVA5OjxxYU6=
115 MoC0SpVv[3Srb36gRZN{[Xl? NVfIS2pEPSEQvF2= M{WyS|Q5KGh? MnrOSG1UVw>? NEnEUGZqdmS3Y3XzJJA2Oy2mZYDlcoRmdnRic3Xu[ZNk\W6lZdMg NHrUfII9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NUC2O|c5Pyd-MkWwOlc4QDd:L3G+
A498 MXvGeY5kfGmxbjDBd5NigQ>? NEj5TXY2KM7:TR?= Ml[zOFghcA>? MlfsSG1UVw>? M3qxWIlv\HWlZYOgdFU{NWSncHXu[IVvfCC|ZX7ld4NmdmOnwrC= NYi3PGV[RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkWwOlc4QDdpPkK1NFY4Pzh5PD;hQi=>
Caki-2 NHH0dGRHfW6ldHnvckBCe3OjeR?= Mk[wOUDPxE1? MX:0PEBp NIHLXFFFVVOR NGOwUopqdmS3Y3XzJJA2Oy2mZYDlcoRmdnRic3Xu[ZNk\W6lZdMg NIDDWnY9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NUC2O|c5Pyd-MkWwOlc4QDd:L3G+
ACHN MmPKSpVv[3Srb36gRZN{[Xl? NXLFbVM5PSEQvF2= NFfCSHI1QCCq MlX5SG1UVw>? Mn7EbY5lfWOnczDwOVMu\GWyZX7k[Y51KHOnbnXzZ4Vv[2YEoB?= M2DiTFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ3ME[3O|g4Lz5{NUC2O|c5PzxxYU6=
115 NWLoXo1CT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NIq5WXE2KM7:TR?= Mk[2OFghcA>? NEn6VlRFVVOR NVXaNFJPcW6mdXPld{Bk\WyuIHP5Z4xmKGG{cnXzeOKh NUPlXWwxRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkWwOlc4QDdpPkK1NFY4Pzh5PD;hQi=>
A498 NF;sbmhIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MlnrOUDPxE1? NYrw[49pPDhiaB?= NUjqWnM1TE2VTx?= M1HEV4lv\HWlZYOgZ4VtdCCleXPs[UBienKnc4VCpC=> M3y4b|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ3ME[3O|g4Lz5{NUC2O|c5PzxxYU6=
Caki-2 MYfHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? Mn3xOUDPxE1? NGi5[VM1QCCq MVzEUXNQ MV;pcoR2[2W|IHPlcIwh[3mlbHWgZZJz\XO2wrC= Ml;vQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjVyNke3PFcoRjJ3ME[3O|g4RC:jPh?=
ACHN NI\KcZpIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MnnpOUDPxE1? Mn[5OFghcA>? NFPj[oxFVVOR NV;tNZRLcW6mdXPld{Bk\WyuIHP5Z4xmKGG{cnXzeOKh NVTOd|VLRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkWwOlc4QDdpPkK1NFY4Pzh5PD;hQi=>
115 MVjGeY5kfGmxbjDBd5NigQ>? NIPzfokxNjVxMT:1JO69VQ>? MoTDOFghcA>? NFzHS4RFVVOR MV\s[YFleyC2bzDpcoNz\WG|ZXSg[ZhxemW|c3nvckBw\iCyNUOgZY5lKHOxbXWgdFU{KHSjcnfleEBo\W6nc{qgUWROOixiYX7kJJAzOQ>? MVO8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPTB4N{e4O{c,OjVyNke3PFc9N2F-
A498 NVrPPI9XTnWwY4Tpc44hSXO|YYm= M{PGOVAvPS9zL{Wg{txO MWO0PEBp NV;t[mdJTE2VTx?= M1nkZYxm[WS|IITvJIlv[3KnYYPl[EBmgHC{ZYPzbY9vKG:oIIC1N{BidmRic3;t[UBxPTNidHHy[4V1KGenbnXzPkBOTE1{LDDhcoQheDJz MYi8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPTB4N{e4O{c,OjVyNke3PFc9N2F-
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REH MWfD[YxtKF[rYXLpcIl1gSCDc4PhfS=> NEexNo0xNTJ3IN88US=> NEXKUG9qdmirYnn0d{Bk\WyuII\pZYJqdGm2eTDkc5NmKGSncHXu[IVvfGy7 NU\0bZF{RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkSyOFAzODNpPkK0NlQxOjB|PD;hQi=>
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Lovo  NWjCeFlGTnWwY4Tpc44hSXO|YYm= MYG1M|ExNzJyIN88US=> NXX0TXB6OjRiaB?= NUm1SWJPfXC{ZXf1cIF1\XNicEWzMEBOTE1{LDDwNlEh[W6mIFTSOUBxem:2ZXnuJIxmfmWuczDkc5NmKGSncHXu[IVvfGy7wrC= MVO8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPDF|NkG0O{c,OjRzM{[xOFc9N2F-
A2780 MkXWRZBweHSxc3nzJGF{e2G7 MVm1M|ExNzJyIN88US=> NUXidFZpOjRiaB?= NVXpVm46\W6qYX7j[ZMh[XCxcITvd4l{KGmwZIXjeIlwdiCkeTDENlY6UC:HMUm1VkBwfmW{IILoWHJCUUx? NGPXbZI9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NEGzOlE1Pyd-MkSxN|YyPDd:L3G+
H460 MUnBdI9xfG:|aYOgRZN{[Xl? MU[1M|ExNzJyIN88US=> MUeyOEBp Mnn6[Y5p[W6lZYOgZZBweHSxc3nzJIlv\HWldHnvckBjgSCGMk[5TE9GOTl3UjDveoVzKHKqVGLBTWw> M3\4OFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ2MUO2NVQ4Lz5{NEGzOlE1PzxxYU6=
Lovo  NGHxWXpCeG:ydH;zbZMhSXO|YYm= MWK1M|ExNzJyIN88US=> MXWyOEBp MYXlcohidmOnczDhdI9xfG:|aYOgbY5lfWO2aX;uJIJ6KER{NknIM2UyQTWUIH;2[ZIhemiWUlHJUC=> NUH4TFBNRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkSxN|YyPDdpPkK0NVM3OTR5PD;hQi=>
U87MG M2fQfmZ2dmO2aX;uJIF{e2G7 M1O0eFExKG2rboO= M3jCWmJqdmSrbnegZYZncW6rdImgeI8hVUSPMjDpckBpfW2jbjDVPFdOTyClZXzsd{Bie3Onc4Pl[EBieyCrbnjpZol1cW:wIH;mJG1FVTJxcEWzJJBzd3SnaX6gbY51\XKjY4Tpc44h[W[2ZYKgNVAhdWmwczDifUByfWGwdHn0ZZRqfmVic3Hu[Jdq[2hiaX3teY5wKGG|c3H5MEBKSzVyIE2gNE4yODR3IN88UU4> NUnGSotnRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkewOVA4QDJpPkK3NFUxPzh{PD;hQi=>
U87MG MVLBcpRqeHKxbHnm[ZJifGm4ZTDhd5NigQ>? NEPPdXY1QCCqcoO= M4jPOWFvfGmycn;sbYZmemG2aY\lJIFkfGm4aYT5JIFo[Wmwc4SgbJVu[W5iVUi3UWch[2WubIOg[ZhxemW|c3nu[{B4cWymIIT5dIUheDV|IHHmeIVzKDR6IHjyd{BjgSCPVGOgZZN{[XluIFnDOVAhRSB4LkWg{txONg>? NHXmbXI9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{N{C1NFc5Oid-MkewOVA4QDJ:L3G+
U343MG NUDDbGs3SW62aYDyc4xq\mW{YYTpeoUh[XO|YYm= NGi1WnI1QCCqcoO= NGTEcWpCdnSrcILvcIln\XKjdHn2[UBi[3Srdnn0fUBi\2GrboP0JIh2dWGwIGWzOFNOTyClZXzsd{BmgHC{ZYPzbY5oKHerbHSgeJlx\SCyNUOgZYZ1\XJiNEigbJJ{KGK7IF3UV{Bie3OjeTygTWM2OCB;IEGyMlYh|ryPLh?= NYLUXXJjRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkewOVA4QDJpPkK3NFUxPzh{PD;hQi=>
SW620 MlnlR5l1d3SxeHnjbZR6KGG|c3H5 M{HiUFczKGi{cx?= MYrDfZRwfG:6aXPpeJkh[WejaX7zeEBpfW2jbjDTW|YzOCClZXzsd{Bi\nSncjC3NkBpenNiYomgV3JDKGG|c3H5MEBKSzVyIE2gNE4{QCEQvF2u NEXPU5c9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmwyQTF|M{SvK|5EcEWPQly8M4E,
A549 NX:1SFF1S3m2b4TvfIlkcXS7IHHzd4F6 NV70cIRoPzJiaILz NXTaSJhCS3m2b4TvfIlkcXS7IHHnZYlve3RiaIXtZY4hSTV2OTDj[YxteyCjZoTldkA4OiCqcoOgZpkhW1KEIHHzd4F6NCCLQ{WwJF0hOC52MTFOwG0v NH:5bXM9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmwyQTF|M{SvK|5EcEWPQly8M4E,
SJSA1 MVLDfZRwfG:6aXPpeJkh[XO|YYm= MkDXO|IhcHK| NEDTTWJEgXSxdH;4bYNqfHliYXfhbY5{fCCqdX3hckBUUlODMTDj[YxteyCjZoTldkA4OiCqcoOgZpkhW1KEIHHzd4F6NCCLQ{WwJF0hOS56MTFOwG0v MoLBQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xd4f3MoVjcS6jYz71b{9kcGWvYnyvZ49ueG:3bnTfdoVxd3K2X3PhdoQwS0iHTVLMNVkyOzN2Lze+R4hGVUKOPD;hQi=>
HCT116 MlS3R5l1d3SxeHnjbZR6KGG|c3H5 MlPYO|IhcHK| MV7DfZRwfG:6aXPpeJkh[WejaX7zeEBpfW2jbjDIR3QyOTZiY3XscJMh[W[2ZYKgO|IhcHK|IHL5JHNTSiCjc4PhfUwhUUN3MDC9JFQvPjNizszNMi=> NUPVR|JCRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNOTlzM{O0M{c,S2iHTVLMQE9iRg>?
PC3 MV;DfZRwfG:6aXPpeJkh[XO|YYm= NV;PR5lOPzJiaILz M1PDfmN6fG:2b4jpZ4l1gSCjZ3HpcpN1KGi3bXHuJHBEOyClZXzsd{Bi\nSncjC3NkBpenNiYomgV3JDKGG|c3H5MEBKSzVyIE2gOk4{PyEQvF2u MWK8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQlyxPVE{OzRxJ{7DbGVOSkx:L3G+

... Click to View More Cell Line Experimental Data

Assay
Methods Test Index PMID
Western blot
MDM2 / p53 / ALKBH2 / p21 / PUMA; 

PubMed: 23258843     


CCF-STTG1 cells were treated with the MDM2 antagonist nutlin-3 (0–8 µM) for 24h before cell lysates were collected for western blotting.

RRM1 / RRM2 / p53R2 / p21 / p53 / pS6 / S6; 

PubMed: 28507282     


(A) Rh18 cells were treated with different concentrations of nutlin-3 as indicated for 24 hr. Total proteins were extracted for immunoblotting of RRM1, RRM2, γH2AX, p21, p53R2, p53, S6, pS6-235/6 and 4E-BP1. (B) Rh30 cells were treated with different concentrations of nutlin-3 as indicated for 24 hr. Total proteins were extracted for immunoblotting of RRM1, RRM2, γH2AX, p21, p53R2, p53, S6, pS6-235/6 and 4E-BP1. GAPDH and Actin served as loading controls.

23258843 28507282
Immunofluorescence
Lamin A / Lamin C / p16 / H3K9me3; 

PubMed: 30728349     


c Immunofluorescence images of nuclear deformation and p16 expression after Nutlin-3 treatment for different time period. HCT p53+/− cells were treated with Nutlin-3 (1 μM) for different time (24, 48 h). After treatment, cells were subjected to immunofluorescence staining for Lamin A/C (Red), p16 (Green), and counterstained with DAPI (Blue). dImmunofluorescence images of nuclear deformation and decreased expression of H3K9me3 in HCT p53+/− cells (left). Counting of histone H3K9me3-positive cells (middle) and signal intensities (right) on the basis of IF staining. HCT p53+/− cells were treated with Nutlin-3 (1 μM) for different time (24, 48 h). After treatment, cells were IF stained with Lamin A/C (Red), H3K9me3 (Green), and counterstained with DAPI (Blue). *P < 0.05. 

Merlin / cyclin D1 / p53 / MDM2; 

PubMed: 30274821     


The changes in the subcellular localization of proteins in response to Nutlin-3. Nuclear merlin was indicated with white arrows. Scale bar = 50 μm.

p53; 

PubMed: 24286312     


The subcellular localization of p53 was detected under immunofluorescence microscope (1,000×). The cells were treated as indicated and stained for p53 (red). Nuclei were counterstained with DAPI (blue).

30728349 30274821 24286312
Growth inhibition assay
Cell viability; 

PubMed: 29286113     


Inhibitory effect of nutlin-3 for the cell proliferation after cultivate cells at different concentration for three times (24, 48 and 72 h), respectively.

29286113
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. [1]

Protocol

Kinase Assay:

[1]

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Biacore study:

Competition assay is performed on a Biacore S51. A Series S Sensor chip CM5 is utilized for the immobilization of a PentaHis antibody for capture of the His-tagged p53. The level of capture is ~200 response units (1 response unit corresponds to 1 pg of protein per mm2). The concentration of MDM2 protein is kept constant at 300 nM. Nutlin-3 is dissolved in DMSO at 10 mM and further diluted to make a concentration series of Nutlin-3 in each MDM2 test sample. The assay is run at 25 °C in running buffer (10 mM Hepes, 0.15 M NaCl, 2% DMSO). MDM2-p53 binding in the presence of Nutlin-3 is calculated as a percentage of binding in the absence of Nutlin-3 and IC50 is calculate
Cell Research:

[1]

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  • Cell lines: HCT116, RKO, SJSA-1, SW480, and MDA-MB-435
  • Concentrations: Dissolved in DMSO, final concentrations ~ 30 μM
  • Incubation Time: 8, 24, and 48 hours
  • Method:

    Cells are exposed to various concentrations of Nutlin-3 for 8, 24 and 48 hours. The transcriptional levels of p21 and MDM2 genes are analyzed by real-time PCR, and protein levels by western blotting. Cell viability is measured by the MTT assay. Cell apoptosis is determined by terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling (TUNEL) staining with flow cytometry and fluorescence microscopy.


    (Only for Reference)
Animal Research:

[1]

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  • Animal Models: Athymic female nude mice (Nu/Nu-nuBR) injected subcutaneously with SJSA-1 cells
  • Dosages: 200 mg/kg
  • Administration: Orally, twice a day
    (Only for Reference)

Solubility (25°C)

In vitro DMSO 100 mg/mL (171.96 mM)
Ethanol 30 mg/mL (51.59 mM)
Water Insoluble

* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.

Chemical Information

Molecular Weight 581.5
Formula

C30H30Cl2N4O4

CAS No. 890090-75-2
Storage powder
in solvent
Synonyms 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

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Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

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Frequently Asked Questions

  • Question 1:

    Is this a racemic mixture of Nutlin-3a and Nutlin-3b or just the Nutlin-3a enantiomer?

  • Answer:

    It is a racemate.

Mdm2 Signaling Pathway Map

Related Mdm2 Products

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Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID