Nutlin-3a-Nutlin-3a-chiral-DataSheet-生命科學(xué)試劑-MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemENutlin (3a)Cat. No.: HY-10029CAS No.: 675576-98-4Synonyms: Nutlin-3a chiral分式: CHClNO分量: 581.49作靶點(diǎn): MDM-2/p53; Autophagy; Apoptosis作通路: Apoptosis; Autophagy儲(chǔ)存式: Powder -20C 3 years4C 2 yearsIn solvent -80C 6 months-20C 1 month溶解

2、性數(shù)據(jù)體外實(shí)驗(yàn) DMSO : 100 mg/mL (171.97 mM)H2O : 40% PEG300 5% Tween-80 45% salineSolubility: 2.5 mg/mL (4.30 mM); Clear solution2. 請(qǐng)依序添加每種溶劑： 10% DMSO 90% (20% SBE-CD in saline)1/3 Master of Small Molecules 您邊的抑制劑師www.MedChemESolubility: 2.5 mg/mL (4.30 mM); Suspended solution; Need ultrasonic3. 請(qǐng)依序添加每種溶劑

3、： 10% DMSO 90% corn oilSolubility: 2.5 mg/mL (4.30 mM); Clear solutionBIOLOGICAL ACTIVITY物活性 Nutlin 3aNutlin-3 的活性異構(gòu)體，為種雙微體 2 (MDM2) 拮抗劑，抑制 MDM2-p53 相互作，且穩(wěn)定p53 蛋，因此誘導(dǎo)細(xì)胞周 期停滯和細(xì)胞凋亡。IC50 & Target MDM2-p53 1體外研究 Nutlin 3a (Nutlin-3a) is a therapeutic which inhibits MDM2, activates wild-type p53, and ind

4、uces apoptosis-asa therapeutic compound for TP53 wild-type ovarian carcinomas. Three cell lines (HOC-7, OVCA429 andA2780) with wild-type TP53 are highly sensitive to Nutlin 3a (IC50=4 to 6 M). SKOV3 cells have an IC50 of38 M to Nutlin 3a. The two remaining ovarian clear cell lines (TOV21G and OVAS),

5、 both with TP53 wild-type, are relatively more sensitive to growth inhibition with Nutlin 3a (IC50=14 and 25 m respectively) thanthe TP53 mutant cell lines 1. Nutlin 3a (Nutlin-3a) is the active enantiomer of Nutlin-3. Nutlin 3a is a highlyselective MDM2 antagonist and p53 inducer. Seven days of inc

6、ubation with 10 M Nutlin 3a leads to 90%inhibition of NIH/3T3 cellsgrowth but does not affect the proliferation of MEF in which both targets of the drugare eliminated. Nutlin 3a effectively arrestes cell-cycle progression in all cell lines, depleting the S-phasecompartment to 0.2-2% and increasing t

7、he G1- and G2/M-phase compartments, indicating G1 and G2 arrest.The p53 targets p21 and MDM2 are elevated significantly 3 h after Nutlin 3a addition and reach maximallevels at 8 h. Nutlin 3a induces apoptosis in 60% of SJSA-1 and MHM cells after 40 h, which increasefurther after 60 h (85% and 65%, r

8、espectively) 2.體內(nèi)研究 Nutlin 3a (Nutlin-3a) is efficacious in all models with average tumor growth inhibition 98%. Nutlin 3asuppresses xenograft growth in a dose-dependent fashion with the highest dose (200 mg/kg) showing asubstantial tumor shrinkage (eight partial and one full regressions). The estab

9、lished SJSA-1 and MHMosteosarcoma xenografts with Nutlin 3a causes extensive tumor regression 2.PROTOCOLCell Assay 1 All 15 cell lines are plated at a density of 1103 cells per well in 96-well plates. After 24h, media isexchanged and cells are treated with incremental concentrations of Nutlin 3a (1

10、M, 5 M, 10 M, 25 M, 50M, and 70 M). After 72 h of incubation, WST-1 is added to each well, and a microplate reader is used at anabsorbance of 450 nm to measure the number of remaining viable cells. Experiments are repeated withsmaller titrations of Nutlin 3a as needed to determine the exact IC50 of

11、cell lines. The IC50 is defined. Celllines are again plated in a manner identical to above and treated with Nutlin 3a at their respective IC50, andWST-1 is added with cell viability measurement at 24, 48, and 72h 1.MCE has not independently confirmed the accuracy of these methods. They are for refer

12、ence only.Animal Mice 22/3 Master of Small Molecules 您邊的抑制劑師www.MedChemEAdministration 2 Nude mice bearing s.c. tumor xenografts (10 mice per group in the SJSA-1, LnCaP, and 22Rv1 study and 15mice per group in the MHM study) are dosed orally twice daily with Nutlin 3a (50-200 mg/kg) or vehicle (1%Kl

13、ucel, 0.1% Tween 80) for 2 weeks (22Rv1 and LnCap) or 3 weeks (SJSA-1 and MHM). Tumor volume ismeasured with a caliper and calculated. For Western blot analysis, nude mice with established SJSA-1tumors (200-400 mm3, three animals per group are treated with three doses of Nutlin 3a at 150 mg/kg (at 0

14、,8, and 24 h), and tumors are harvested 3 h after the last dose. Tumor samples are flash-frozen andprocessed 2.MCE has not independently confirmed the accuracy of these methods. They are for reference only.戶使本產(chǎn)品發(fā)表的科研獻(xiàn) Cell Rep. 2019 Apr 23;27(4):1176-1189.e5. J Mater Chem B. 2017, 5, 5816-5834. Eur

15、J Med Chem. 2016 May 23;114:328-36. Biochim Biophys Acta Mol Cell Res. 2019 Aug;1866(8):1272-1281. J Endocrinol. 2018 Apr;237(1):1-14.See more customer validations on HYPERLINK / www.MedChemEREFERENCES1. Crane EK, et al. Nutlin-3a: A Potential Therapeutic Opportunity for TP53 Wild-Type Ovarian Carci

16、nomas. PLoS One. 2015 Aug6;10(8):e0135101.2. Tovar C, et al. Small-molecule MDM2 antagonists reveal aberrant p53 signaling in cancer: implications for therapy. Proc Natl Acad Sci US A. 2006 Feb 7;103(6):1888-93.3. M Ulrich, et al. Murine tumor models for the in vivo evaluation of natural compounds and their derivatives