Nutlin-3

目錄號(hào)：S1061 Purity: 99.59%

Nutlin-3是一種有效的，選擇性Mdm2(它自身和p53的環(huán)指依賴性泛素蛋白連接酶)拮抗劑，無細(xì)胞試驗(yàn)中IC50為90 nM；可穩(wěn)定p53缺陷細(xì)胞中的p73。

Nutlin-3 Chemical Structure

CAS: 890090-75-2

規(guī)格	價(jià)格	庫(kù)存
10mM (1mL in DMSO)	1515.15	現(xiàn)貨
5mg	900.36	現(xiàn)貨
25mg	3026.07	現(xiàn)貨
100mg	7939.67	現(xiàn)貨
1g	24488.1	現(xiàn)貨
更大包裝有超大折扣
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產(chǎn)品質(zhì)控

批次：純度： 99.59%

99.59

常與Nutlin-3一起在實(shí)驗(yàn)中被使用的化合物

Sorafenib (BAY 43-9006)

Nutlin-3和Sorafenib聯(lián)合使用可增加p53(wild-type) OCI-AML3及p53(deleted) HL-60細(xì)胞的凋亡和自噬。

Tozasertib (VX-680)

Nutlin-3和Tozasertib聯(lián)合療法選擇性殺死p53受損細(xì)胞并抑制表達(dá)野生型p53的細(xì)胞增殖。

Rucaparib (AG014699)

Nutlin-3和Rucaparib增強(qiáng)TP53卵巢癌細(xì)胞(A2780和IGROV-1細(xì)胞)的細(xì)胞死亡和G2/M細(xì)胞周期的百分比。

Aspirin

Nutlin-3和Aspirin抑制HepG2細(xì)胞的增殖和凋亡，并減少體內(nèi)腫瘤體積和腫瘤血管生成。

Nutlin-3相關(guān)產(chǎn)品

相關(guān)產(chǎn)品	Nutlin-3a RG-7112 Idasanutlin (RG7388) SAR405838 NSC 207895 NVP-CGM097 Siremadlin (HDM201) Nutlin-3b YH239-EE MX69	點(diǎn)擊展開
相關(guān)化合物庫(kù)	自噬化合物庫(kù) 凋亡分子化合物庫(kù) 鐵死亡化合物庫(kù) 細(xì)胞焦亡化合物庫(kù) 線粒體靶向化合物庫(kù)	點(diǎn)擊展開

細(xì)胞實(shí)驗(yàn)數(shù)據(jù)示例

細(xì)胞系	實(shí)驗(yàn)類型	給藥濃度	孵育時(shí)間	活性描述	文獻(xiàn)信息(PMID)
SK-BR-7	Function Assay	10?μM	24 h	inhibits TGF-β3-induced EPHB2?mRNA and protein expression	25257729
SUM102PT	Function Assay	10?μM	24 h	inhibits TGF-β3-induced EPHB2?mRNA and protein expression	25257729
RAW 264.7	Function Assay	10?μM	30 min	prevents the p53 reduction in response to LPS	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	inhibits LPS-induced NO production?	25172547
MCF7?	Cell Viability Assay	2.5 μM	5 d	sensitizes MCF7 to PARP inhibition	25085902
MCF7?	Function Assay	2.5 μM	48 h	decreases the homologous DSB repair frequencies	25085902
ACHN	Cell Viability Assay	0.5-10 μM	0-6 d	inhibits proliferation in a dose-dependent manner	25067787
Caki-2	Cell Viability Assay	0.5-10 μM	0-6 d	inhibits proliferation in a dose-dependent manner	25067787
A498	Cell Viability Assay	0.5-10 μM	0-6 d	inhibits proliferation in a dose-dependent manner	25067787
115	Cell Viability Assay	0.5-10 μM	0-6 d	inhibits proliferation in a dose-dependent manner	25067787
117	Cell Viability Assay	0.5-10 μM	0-6 d	inhibits proliferation in a dose-dependent manner	25067787
ACHN	Function Assay	0.5/1/5 μM	48 h	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	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	leads to increased expression of p53 and some p53 target genes: MDM2, and p21	25067787
115	Function Assay	0.5/1/5 μM	48 h	leads to increased expression of p53 and some p53 target genes: MDM2, and p21	25067787
ACHN	Growth Inhibition Assay	5 μM	48 h	induces cell cycle arrest?	25067787
Caki-2	Growth Inhibition Assay	5 μM	48 h	induces cell cycle arrest?	25067787
A498	Growth Inhibition Assay	5 μM	48 h	induces cell cycle arrest?	25067787
115	Growth Inhibition Assay	5 μM	48 h	induces cell cycle arrest?	25067787
ACHN	Function Assay	5 μM	48 h	induces p53-dependent senescence?	25067787
Caki-2	Function Assay	5 μM	48 h	induces p53-dependent senescence?	25067787
A498	Function Assay	5 μM	48 h	induces p53-dependent senescence?	25067787
115	Function Assay	5 μM	48 h	induces p53-dependent senescence?	25067787
MOLM-13	Function Assay	6?μM	0-8 h	increases the levels of p53, MDM2, p21 and acetylated p53	24885082
MOLM-13	Function Assay	6?μM	6 h	enhances the acetylation of histone H2B and heat shock proteins Hsp27 and Hsp90	24885082
U2OS?	Function Assay	20 μM	24 h	increases the mRNA levels of?BCL2A1, BCLXL?andBCLW	24867259
AML2	Apoptosis Assay	2/10 μM	24/48 h	induces apoptosis	24659749
MOML13	Apoptosis Assay	2/10 μM	24/48 h	induces apoptosis	24659749
AML2	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
MOML13	Function Assay	10μM	2/4 h	increases the level of p53	24659749
BeWo	Function Assay	30 μM	24 h	increases p53, Mdm2, p21 and Puma at the protein level	24498154
BeWo	Apoptosis Assay	30 μM	24 h	increases apoptosis	24498154
OCI	Function Assay	10 μM	24 h	upregulates the SOCS-1 expression	24473562
MOLM	Function Assay	10 μM	24 h	upregulates the SOCS-1 expression	24473562
U2OS?	Function Assay	20 μM	24 h	increases the levels of the HO-1 protein as well as the p53 protein	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	induces HO-1 expression at the level of transcription	24366007
RKO	Function Assay	20 μM	24 h	induces HO-1 expression at the level of transcription	24366007
SMMC-7721?	Cell Viability Assay	1.25-20 μM	24/48/72 h	inhibits cell proliferation dose and time dependently	24286312
HuH-7	Cell Viability Assay	1.25-20 μM	24/48/72 h	inhibits cell proliferation dose and time dependently	24286312
SMMC-7721?	Apoptosis Assay	20 μM	48 h	induces apoptosis	24286312
HuH-7	Apoptosis Assay	20 μM	48 h	induces apoptosis	24286312
SMMC-7721?	Function Assay	10 μM	36 h	down-regulates the protein expression level of phospho-Ser392-p53	24286312
MCF-10CA1a	Function Assay	10?μM	24 h	inhibits TGF-β3-induced EPHB2?mRNA and protein expression	25257729
MCF-10CA1a	Function Assay	10?μM	24 h	decreases the TGF-β3-induced mRNA levels ofMMP2,?MMP9, and?integrin?β?3	25257729
MCF-10A1?	Function Assay	10?μM	24/48 h	inhibits migration of normal breast epithelial?	25257729
MCF-10CA1a	Function Assay	10?μM	48 h	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?	decreases the FoxM1 levels	25426548
NCI-H23	Function Assay	10?μM	21h?	decreases the FoxM1 levels	25426548
A2780	Function Assay	10?μM	21h?	increases p53 protein levels	25426548
NCI-H23	Function Assay	10?μM	21h?	increases p53 protein levels	25426548
OVCAR10	Function Assay	10?μM	21h?	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	causes the ectopic expression of IFI16	25544361
SMMC-7721	Function Assay	10 μM	48 h	increases the expression level of?IFNB1?mRNA	25544361
SMMC-7721	Function Assay	10 μM	48 h	induces the chromatin-bound protein IFI16 to partially localize in the cytoplasm?	25544361
SMMC-7721	Function Assay	10 μM	48 h	causes DNA DSB damage	25544361
DU4475?	Function Assay	5/10/20 μM	24?h	downregulates Toca-1 dose dependently	25547174
C2C12	Growth Inhibition Assay	10?μM?	24/48/72 h	inhibits cells proliferation and differentiation	25871794
L6	Growth Inhibition Assay	10?μM?	24/48/72 h	inhibits cells proliferation and differentiation	25871794
C666-1	Apoptosis Assay	10 μM	48/72 h	sensitizes C666-1 cells to cisplatin-induced apoptosis	26252575
C666-1?	Function Assay	10 μM	24 h	activates the p53 pathway, upregulating p53, p21 and Mdm2	26252575
C666-1	Cell Viability Assay	10 μM	48 h	sensitizes C666-1 cells to the cytotoxic effect of cisplatin	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	down-regulates the protein expression level of phospho-Ser392-p53	24286312
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
MCF-7?	Function Assay	10?μM		inhibits cyclin D1 and Dicer?	25702703
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
HepG2	Growth Inhibition Assay		72 h	IC50=35.86 ± 2.9 μM	24884809
HepG2/As	Growth Inhibition Assay		72 h	IC50=68.13 ± 9.6 μM	24884809
SMMC7721	Growth Inhibition Assay		72 h	IC50=31.28 ± 4.2 μM	24884809
SMMC7721/Ac	Growth Inhibition Assay		72 h	IC50=55.21 ± 5.03 μM	24884809
Huh-7	Growth Inhibition Assay		72 h	IC50=33.96 ± 3.9 μM	24884809
Hep3B	Growth Inhibition Assay		72 h	IC50=20.18 ± 1.84 μM	24884809
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
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
HepG2	Apoptosis Assay			induces apoptosis	24884809
SMMC7721	Apoptosis Assay			induces apoptosis	24884809
Huh-7	Apoptosis Assay			induces apoptosis	24884809
Hep3B	Apoptosis Assay			induces apoptosis	24884809
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
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生物活性

產(chǎn)品描述

靶點(diǎn)

MDM2 ^[5]
(Cell-free assay)

180 nM

體外研究(In Vitro)
體外研究活性	Nutlin-3有效抑制MDM2-p53相互作用，IC50 為 90 nM, 導(dǎo)致p53通路激活。Nutlin-3 處理含野生型p53的細(xì)胞，如HCT116, RKO 和SJSA-1,誘導(dǎo)MDM2 和p21表達(dá), 且具有有效的抗增殖活性，IC50 為~1.5 μM, 但是作用于含突變型p53的細(xì)胞系 SW480和 MDA-MB-435沒有效果。10 μM Nutlin-3處理 SJSA-1細(xì)胞48小時(shí)，顯著誘導(dǎo)caspase依賴的細(xì)胞凋亡，凋亡達(dá)~45%。雖然Nutlin-3也抑制人皮膚 (1043SK) 和小鼠胚胎 (NIH/3T3) 的生長(zhǎng)和活力，IC50分別為2.2 μM 和1.3 μM, 10 μM Nutlin-3處理一周后仍保留細(xì)胞活力，而3 μM Nutlin-3 處理SJSA-1細(xì)胞后，細(xì)胞則無活力。^[1] Nutlin-3 不誘導(dǎo)p53在關(guān)鍵絲氨酸殘基的磷酸化，在特定DNA結(jié)合序列沒有區(qū)別，且與基因毒性藥物Doxorubicin誘導(dǎo)的磷酸化p53相比，使p53靶點(diǎn)基因轉(zhuǎn)活，說明 p53 在關(guān)鍵絲氨酸殘基的磷酸化對(duì)轉(zhuǎn)錄激活和凋亡是非必需的。^[2] 雖然與MDM2相比，Nutlin-3 與MDMX 結(jié)合的效率低一點(diǎn), Nutlin-3作用于視網(wǎng)膜母細(xì)胞瘤細(xì)胞(Weri1)，能抑制MDMX–p53相互作用，且誘導(dǎo) p53通路，IC50為0.7 μM。^[3] 30 μM Nutlin-3作用于無野生型p53的細(xì)胞，也擾亂內(nèi)源性p73-HDM2 相互作用，且增強(qiáng)p73穩(wěn)定性和促凋亡活性, 導(dǎo)致細(xì)胞生長(zhǎng)受抑制，和誘導(dǎo)凋亡。^[4]
激酶實(shí)驗(yàn)	Biacore 研究
激酶實(shí)驗(yàn)	在Biacore S51上進(jìn)行競(jìng)爭(zhēng)性實(shí)驗(yàn)。衍生一系列S傳感器芯片CM5，用于固定 PentaHis抗體，為了捕獲 His-標(biāo)記的p53。捕獲的水平為~200反應(yīng)單位(1 反應(yīng)單位對(duì)應(yīng)于1 pg 蛋白/ mm²)。MDM2蛋白濃度一直維持在300 nM。Nutlin-3 溶于DMSO，濃度為10 mM，然后進(jìn)一步稀釋，在每個(gè)MDM2實(shí)驗(yàn)樣本中產(chǎn)生系列濃度的Nutlin-3。在電泳緩沖液(10 mM Hepes,0.15 M NaCl, 2% DMSO)中25^oC下進(jìn)行實(shí)驗(yàn)。在Nutlin-3存在時(shí)，計(jì)算MDM2-p53結(jié)合情況，作為結(jié)合百分?jǐn)?shù)，使用Microsoft Excel計(jì)算IC50。
細(xì)胞實(shí)驗(yàn)	細(xì)胞系	HCT116, RKO, SJSA-1, SW480, 和 MDA-MB-435
	濃度	溶于DMSO,終濃度為~ 30 μM
	孵育時(shí)間	8, 24, 和 48 小時(shí)
	方法	使用不同濃度Nutlin-3處理細(xì)胞8, 24和 48 小時(shí)。通過實(shí)時(shí)PCR分析p21 和MDM2基因轉(zhuǎn)錄水平,通過Western Blotting分析蛋白水平。通過MTT實(shí)驗(yàn)測(cè)定細(xì)胞活力。通過末端脫氧核苷酸轉(zhuǎn)移酶調(diào)節(jié)的脫氧尿苷三磷酸缺口末端標(biāo)記法（TUNEL）染色，使用流式細(xì)胞儀和熒光顯微鏡測(cè)定細(xì)胞凋亡。
實(shí)驗(yàn)圖片	檢測(cè)方法	檢測(cè)指標(biāo)	實(shí)驗(yàn)圖片	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

體內(nèi)研究(In Vivo)
體內(nèi)研究活性	Nutlin-3 按200 mg/kg 劑量口服處理，每天兩次，持續(xù)3周，顯著抑制SJAS-1移植瘤生長(zhǎng)，抑制達(dá)90%, 而Doxorubicin抑制81%腫瘤生長(zhǎng)。^[1]
動(dòng)物實(shí)驗(yàn)	Animal Models	皮下注射 SJSA-1細(xì)胞的雌性無胸腺Nu/Nu-nuBR裸鼠
	Dosages	200 mg/kg
	Administration	口服處理，每天兩次

參考文獻(xiàn)
[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 + 展開

參考文獻(xiàn)

[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

+ 展開