Home Apoptosis MDM2/MDMX antagonist Nutlin-3

연구용

Nutlin-3 p53-MDM2 Inhibitor

제품 번호S1061

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

화학 구조

분자량: 581.5

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품질 관리 (Quality Control)

배치: 순도: 99.59%
99.59

함께 자주 사용되는 제품 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.

세포 배양, 처리 및 작업 농도
(Cell Culture, Treatment & Working Concentration)

세포주 분석 유형 농도 배양 시간 제형 활성 설명 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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화학 정보, 보관 및 안정성 (Chemical Information, Storage & Stability)

분자량 581.5 화학식

C30H30Cl2N4O4

 보관 (수령일로부터)
CAS 번호 890090-75-2 SDF 다운로드 원액 보관

동의어 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

용해도 (Solubility)

In vitro
배치:

DMSO : 100 mg/mL (171.96 mM)
(수분으로 오염된 DMSO는 용해도를 감소시킬 수 있습니다. 신선하고 무수 DMSO를 사용하십시오.)

Ethanol : 100 mg/mL

Water : Insoluble

몰농도 계산기

질량 농도 부피 분자량
희석 계산기 분자량 계산기

In vivo
배치:

생체 내 제형 계산기 (투명한 용액)

1단계: 아래 정보 입력 (권장: 실험 중 손실을 고려하여 추가 동물 포함)

mg/kg g μL

2단계: 생체 내 제형 입력 (이것은 계산기일 뿐 제형이 아닙니다. 용해도 섹션에 생체 내 제형이 없는 경우 먼저 당사에 문의하십시오.)

% DMSO % % Tween 80 % ddH2O
%DMSO %

계산 결과:

작업 농도: mg/ml;

DMSO 원액 준비 방법: mg 약물 사전 용해 μL DMSO ( 원액 농도 mg/mL, 농도가 해당 약물 배치의 DMSO 용해도를 초과하는 경우 먼저 당사에 문의하십시오. )

생체 내 제형 준비 방법: 취하다 μL DMSO 원액, 다음 추가μL PEG300, 혼합하고 투명하게 한 다음 추가μL Tween 80, 혼합하고 투명하게 한 다음 추가 μL ddH2O, 혼합하고 투명하게 합니다.

생체 내 제형 준비 방법: 취하다 μL DMSO 원액, 다음 추가 μL 옥수수 기름, 혼합하고 투명하게 합니다.

참고: 1. 다음 용매를 추가하기 전에 액체가 투명한지 확인하십시오.
2. 용매를 순서대로 추가해야 합니다. 다음 용매를 추가하기 전에 이전 추가에서 얻은 용액이 투명한 용액인지 확인해야 합니다. 와동, 초음파 또는 뜨거운 물 중탕과 같은 물리적 방법을 사용하여 용해를 도울 수 있습니다.

작용 메커니즘 (Mechanism of Action)

Targets/IC50/Ki
MDM2
(Cell-free assay)
180 nM
시험관 내(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.

키나아제 분석
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 this compound 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 this chemical is calculated as a percentage of binding in the absence of it and IC50 is calculate
생체 내(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.

참조
  • [4] https://pubmed.ncbi.nlm.nih.gov/17700533/
  • [5] http://eprints.lib.hokudai.ac.jp/dspace/bitstream/2115/54893/1/Masaki_Miyazaki.pdf

적용 분야 (Applications)

방법 바이오마커 이미지 PMID
Western blot MDM2 / p53 / ALKBH2 / p21 / PUMA RRM1 / RRM2 / p53R2 / p21 / p53 / pS6 / S6
S1061-WB1
23258843
Immunofluorescence Lamin A / Lamin C / p16 / H3K9me3 Merlin / cyclin D1 / p53 / MDM2 p53
S1061-IF1
30728349
Growth inhibition assay Cell viability
S1061-viability1
29286113

자주 묻는 질문 (Frequently Asked Questions)

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

답변:
It is a racemate.