Nutlin-3 | Nutlin-3a | CAS#675576-98-4 | 675576-97-3 | p53/MDM2 inhibitor

MedKoo Cat#: 406308 | Name: Nutlin-3a

Description:

WARNING: This product is for research use only, not for human or veterinary use.

Nutlin-3a, also known as SML 0580, is an inhibitor of MDM2 (human homolog of murine double minute 2), which disrupts its interaction with p53, leading to the stabilization and activation of p53. Nutlin-3a activates the p53 pathway and efficiently induces apoptosis in tumours with amplified MDM2 gene and overexpression of MDM2 protein. Nutlin-3 enhances the bortezomib sensitivity of p53-defective cancer cells by inducing paraptosis.

Chemical Structure

Nutlin-3a

CAS#675576-98-4 (4S5R)

Theoretical Analysis

MedKoo Cat#: 406308

Name: Nutlin-3a

CAS#: 675576-98-4 (4S5R)

Chemical Formula: C30H30Cl2N4O4

Exact Mass: 580.1644

Molecular Weight: 581.49

Elemental Analysis: C, 61.97; H, 5.20; Cl, 12.19; N, 9.64; O, 11.01

Price and Availability

Size	Price	Availability
5mg	USD 110.00	Ready to ship
10mg	USD 200.00	Ready to ship
25mg	USD 450.00	Ready to ship
50mg	USD 750.00	Ready to ship
100mg	USD 1,150.00	Ready to ship
200mg	USD 1,750.00	Ready to Ship
500mg	USD 3,050.00	Ready to Ship

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Related CAS #

675576-98-4 (4S5R) 548472-68-0 (4R5S and 4S5R) 675576-97-3 (4R5S)

Synonym

Nutlin3a; Nutlin 3a; Nutlin-3a; SML 0580; SML0580; SML-0580; (-)-Nutlin 3, (-)-Nutlin-3;

IUPAC/Chemical Name

4-((4S,5R)-4,5-bis(4-chlorophenyl)-2-(2-isopropoxy-4-methoxyphenyl)-4,5-dihydro-1H-imidazole-1-carbonyl)piperazin-2-one

InChi Key

BDUHCSBCVGXTJM-WUFINQPMSA-N

InChi Code

InChI=1S/C30H30Cl2N4O4/c1-18(2)40-25-16-23(39-3)12-13-24(25)29-34-27(19-4-8-21(31)9-5-19)28(20-6-10-22(32)11-7-20)36(29)30(38)35-15-14-33-26(37)17-35/h4-13,16,18,27-28H,14-15,17H2,1-3H3,(H,33,37)/t27-,28+/m0/s1

SMILES Code

O=C1NCCN(C(N2[C@H](C3=CC=C(Cl)C=C3)[C@H](C4=CC=C(Cl)C=C4)N=C2C5=CC=C(OC)C=C5OC(C)C)=O)C1

Appearance

Solid powder

Purity

>98% (or refer to the Certificate of Analysis)

Shipping Condition

Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition

Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility

Soluble in DMSO, not in water

Shelf Life

>2 years if stored properly

Drug Formulation

This drug may be formulated in DMSO

Stock Solution Storage

0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code

2934.99.9001

More Info

Nutlins are cis-imidazoline analogs which inhibit the interaction between MDM2 and tumour suppressor p53, and were discovered by screening a chemical library by Vassilev et al. Nutlin-1, Nutlin-2 and Nutlin-3 were all identified in the same screen, however Nutlin-3 is the compound most commonly used in anti-cancer studies. Inhibiting the interaction between mdm2 and p53 stabilizes p53 and is thought to selectively induce a growth-inhibiting state called senescence in cancer cells. These compounds are therefore thought to work best on tumors that contain normal or wild type p53.[citation needed] Nutlin-3 has been shown to affect the production of p53 within minutes. (source: http://en.wikipedia.org/wiki/Nutlin).

Product Data

Product Data

Certificate of Analysis

View CoA: current batch, Lot# T22D03P02

QC Data

View QC data: current batch, Lot# T22D03P02

Safety Data Sheet (SDS)

View Safety Data Sheet (SDS)

Instruction

View handling instruction

Biological target:

Nutlin-3a, an active enantiomer of Nutlin-3, is a potent murine double minute (MDM2) inhibitor (IC50=90 nM).

In vitro activity:

Fifteen epithelial ovarian cancer cell lines of varying histologic subtypes were treated with Nutlin-3a with determination of IC50 values. Western Blot (WB) and quantitative real-time polymerase chain reaction (qRT-PCR) analyses quantified MDM2, p53, and p21 expression after Nutlin-3a treatment. DNA from 15 cell lines was then sequenced for TP53 mutations in exons 2-11 including intron-exon boundaries. Responses to Nutlin-3a were dependent upon TP53 mutation status. By qRT-PCR and WB, levels of MDM2 and p21 were upregulated in wild-type TP53 sensitive cell lines, and p21 induction was reduced or absent in mutant cell lines. Annexin V assays demonstrated apoptosis in sensitive cell lines treated with Nutlin-3a. Reference: PLoS One. 2015 Aug 6;10(8):e0135101. https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/26248031/

In vivo activity:

To increase its potency the active enantiomer nutlin-3a was purified and a 3-week antitumor efficacy study in SJSA-1 tumor-bearing nude mice was performed(Fig. 6A). Nutlin-3a suppressed xenograft growth in a dose-dependent fashion with the highest dose (200 mg/kg) showing a substantial tumor shrinkage (eight partial and one full regressions). No weight loss or significant pathological changes were recorded during the course of the study (data not shown). To show that the antitumor effect of nutlin-3a is caused by activation of the p53 pathway we analyzed the level of p53 targets p21 and MDM2 in nutlin-treated SJSA-1 xenografts. Western blot analysis revealed accumulation of both proteins in tumors from nutlin-treated animals but not vehicle controls (Fig. 6B). This experiment is consistent with the hypothesis that the in vivo antitumor effect of nutlin-3 is derived from activation of the p53 pathway. To exclude any possibility for an in vivo-related artifact we also tested nutlin-3a on cells with mutant p53. Colon cancer cell line HT29 expresses mutant p53 and does not respond to nutlin-3a treatment in vitro (data not shown). Nude mice bearing established HT29 xenografts were treated orally with 200 mg/kg nutlin-3 for 3 weeks. In agreement with the in vitro results, HT29 xenografts showed undistinguishable growth characteristics in the presence or absence of nutlin-3 (data not shown). These experiments confirmed that nutlin-3 is a selective activator of the p53 pathway in vivo and highly efficacious against SJSA-1 osteosarcoma tumors. Reference: Proc Natl Acad Sci U S A. 2006 Feb 7;103(6):1888-93. https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/16443686/

	Solvent	mg/mL	mM
Solubility
	DMSO	25.0	43.00

Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

Preparing Stock Solutions

The following data is based on the product molecular weight 581.49 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Concentration / Solvent Volume / Mass	1 mg	5 mg	10 mg
1 mM	1.15 mL	5.76 mL	11.51 mL
5 mM	0.23 mL	1.15 mL	2.3 mL
10 mM	0.12 mL	0.58 mL	1.15 mL
50 mM	0.02 mL	0.12 mL	0.23 mL

Formulation protocol:

In vitro protocol:

1. Crane EK, Kwan SY, Izaguirre DI, Tsang YT, Mullany LK, Zu Z, Richards JS, Gershenson DM, Wong KK. Nutlin-3a: A Potential Therapeutic Opportunity for TP53 Wild-Type Ovarian Carcinomas. PLoS One. 2015 Aug 6;10(8):e0135101. doi: 10.1371/journal.pone.0135101. PMID: 26248031; PMCID: PMC4527847. 2. Kobayashi M, Ishizaki Y, Owaki M, Matsumoto Y, Kakiyama Y, Hoshino S, Tagawa R, Sudo Y, Okita N, Akimoto K, Higami Y. Nutlin-3a suppresses poly (ADP-ribose) polymerase 1 by mechanisms different from conventional PARP1 suppressors in a human breast cancer cell line. Oncotarget. 2020 May 5;11(18):1653-1665. doi: 10.18632/oncotarget.27581. PMID: 32405340; PMCID: PMC7210013.

In vivo protocol:

1. Tovar C, Rosinski J, Filipovic Z, Higgins B, Kolinsky K, Hilton H, Zhao X, Vu BT, Qing W, Packman K, Myklebost O, Heimbrook DC, Vassilev LT. Small-molecule MDM2 antagonists reveal aberrant p53 signaling in cancer: implications for therapy. Proc Natl Acad Sci U S A. 2006 Feb 7;103(6):1888-93. doi: 10.1073/pnas.0507493103. Epub 2006 Jan 27. PMID: 16443686; PMCID: PMC1413632. 2. Lerche CM, Philipsen PA, Poulsen T, Gniadecki R, Wulf HC. Topical nutlin-3a does not decrease photocarcinogenesis induced by simulated solar radiation in hairless mice. Photodermatol Photoimmunol Photomed. 2012 Aug;28(4):207-12. doi: 10.1111/j.1600-0781.2012.00675.x. PMID: 23017174.

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PMID: 40349458. 4: Azme E, Hasan MM, Ali ML, Alam R, Hoque N, Noushin F, Kabir MF, Islam A, Nipun TS, Hossen SMM, Chung HJ. Computational identification of potential natural terpenoid inhibitors of MDM2 for breast cancer therapy: molecular docking, molecular dynamics simulation, and ADMET analysis. Front Chem. 2025 Apr 16;13:1527008. doi: 10.3389/fchem.2025.1527008. PMID: 40308267; PMCID: PMC12041027. 5: Lu M, Ren Y, Feng S, Wang S, Xia W, Gu B, Shen Y, Yue A, Li N, Zhang Y, Zhong J. MDM2 inhibitor induces apoptosis in colon cancer cells through activation of the CHOP-DR5 pathway, independent of p53 phenotype. Front Pharmacol. 2025 Apr 8;16:1508421. doi: 10.3389/fphar.2025.1508421. PMID: 40264676; PMCID: PMC12011796. 6: Haddad A, Golan-Lev T, Benvenisty N, Goldberg M. Genome-wide screening in human embryonic stem cells identifies genes and pathways involved in the p53 pathway. Mol Med. 2025 Mar 13;31(1):97. doi: 10.1186/s10020-025-01141-5. 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