Nutlin-3a
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MedKoo CAT#: 406308

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

Description: 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

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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: 580.16441
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 Quantity
10.0mg USD 190.0 Ready to ship
25.0mg USD 395.0 Ready to ship
50.0mg USD 695.0 Ready to ship
100.0mg USD 1250.0 Ready to ship
200.0mg USD 2150.0 Ready to ship
500.0mg USD 3850.0 Ready to ship
1.0g USD 4850.0 2 Weeks
2.0g USD 8730.0 2 Weeks
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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

Solubility Data

Solvent Max Conc. mg/mL Max Conc. mM
Solubility
DMSO 25.0 43.0

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.

Recalculate based on batch purity %
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

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1: Yee-Lin V, Pooi-Fong W, Soo-Beng AK. Nutlin-3, A p53-Mdm2 Antagonist for Nasopharyngeal Carcinoma Treatment. Mini Rev Med Chem. 2018;18(2):173-183. doi: 10.2174/1389557517666170717125821. PMID: 28714398; PMCID: PMC5769085.

2: Wang X, Chen Y, Liu H, Guo S, Hu Y, Zhan Y, An H. A novel anti-cancer mechanism of Nutlin-3 through downregulation of Eag1 channel and PI3K/AKT pathway. Biochem Biophys Res Commun. 2019 Sep 24;517(3):445-451. doi: 10.1016/j.bbrc.2019.07.106. Epub 2019 Aug 1. PMID: 31378368.

3: Wang M, Wang X, Li Y, Xiao Q, Cui XH, Xiao GD, Wang JC, Xu CW, Ren H, Liu D. Nutlin-3-Induced Sensitization of Non-Small Cell Lung Cancer Stem Cells to Axitinib-Induced Apoptosis Through Repression of Akt1/Wnt Signaling. Oncol Res. 2019 Sep 23;27(9):987-995. doi: 10.3727/096504018X15424918479652. Epub 2019 Mar 4. PMID: 30832755; PMCID: PMC7848271.

4: He T, Guo J, Song H, Zhu H, Di X, Min H, Wang Y, Chen G, Dai W, Ma J, Sun X, Ma J. Nutlin-3, an Antagonist of MDM2, Enhances the Radiosensitivity of Esophageal Squamous Cancer with Wild-Type p53. Pathol Oncol Res. 2018 Jan;24(1):75-81. doi: 10.1007/s12253-017-0215-5. Epub 2017 Mar 24. PMID: 28341911.

5: Lee DM, Kim IY, Seo MJ, Kwon MR, Choi KS. Nutlin-3 enhances the bortezomib sensitivity of p53-defective cancer cells by inducing paraptosis. Exp Mol Med. 2017 Aug 11;49(8):e365. doi: 10.1038/emm.2017.112. PMID: 28798402; PMCID: PMC5579507.

6: Wu L , Hu Y , He Y , Xia Y , Lu H , Cao Z , Yi X , Wang J . Dual-channel surface plasmon resonance monitoring of intracellular levels of the p53-MDM2 complex and caspase-3 induced by MDM2 antagonist Nutlin-3. Analyst. 2019 Jul 7;144(13):3959-3966. doi: 10.1039/c9an00301k. Epub 2019 May 28. PMID: 31134974.

7: Drost J, van Jaarsveld RH, Ponsioen B, Zimberlin C, van Boxtel R, Buijs A, Sachs N, Overmeer RM, Offerhaus GJ, Begthel H, Korving J, van de Wetering M, Schwank G, Logtenberg M, Cuppen E, Snippert HJ, Medema JP, Kops GJ, Clevers H. Sequential cancer mutations in cultured human intestinal stem cells. Nature. 2015 May 7;521(7550):43-7. doi: 10.1038/nature14415. Epub 2015 Apr 29. PMID: 25924068.

8: Secchiero P, Bosco R, Celeghini C, Zauli G. Recent advances in the therapeutic perspectives of Nutlin-3. Curr Pharm Des. 2011;17(6):569-77. doi: 10.2174/138161211795222586. PMID: 21391907.

9: Voltan R, Secchiero P, Ruozi B, Caruso L, Forni F, Palomba M, Zauli G, Vandelli MA. Nanoparticles loaded with Nutlin-3 display cytotoxicity towards p53(wild-type) JVM-2 but not towards p53(mutated) BJAB leukemic cells. Curr Med Chem. 2013;20(21):2712-22. doi: 10.2174/0929867311320210007. PMID: 23627936.

10: Wu Q, Wang X, Liu J, Zheng J, Liu Y, Li Y, Su F, Ou W, Wang R. Nutlin-3 reverses the epithelial-mesenchymal transition in gemcitabine-resistant hepatocellular carcinoma cells. Oncol Rep. 2016 Sep;36(3):1325-32. doi: 10.3892/or.2016.4920. Epub 2016 Jul 8. PMID: 27430152.

11: Bajelan B, Zaki-Dizaji M, Darabi S, Rajaei F. The effects of Nutlin-3 on morphology, cellular proliferation, and apoptosis in rat primary mesenchymal stem cells. J Cell Physiol. 2019 Jul;234(7):11424-11430. doi: 10.1002/jcp.27798. Epub 2018 Nov 27. PMID: 30478967.

12: Wang XH, Zhang SF, Bao JT, Liu FY. Oridonin synergizes with Nutlin-3 in osteosarcoma cells by modulating the levels of multiple Bcl-2 family proteins. Tumour Biol. 2017 Jun;39(6):1010428317701638. doi: 10.1177/1010428317701638. PMID: 28618955.

13: Bajelan B, Zaki-Dizaji M, Rahmani B, Darzi S, Darabi S, Rajaei F. Resistance of human primary mesenchymal stem cells to cytotoxic effects of nutlin-3 in vitro. J Cell Biochem. 2020 Jan;121(1):788-796. doi: 10.1002/jcb.29324. Epub 2019 Aug 26. PMID: 31452266.

14: Miao R, Xu X, Wang Z, Liu S, Qu K, Chen W, Liu C. Synergistic effect of nutlin-3 combined with aspirin in hepatocellular carcinoma HepG2 cells through activation of Bcl-2/Bax signaling pathway. Mol Med Rep. 2018 Mar;17(3):3735-3743. doi: 10.3892/mmr.2017.8346. Epub 2017 Dec 22. PMID: 29286113; PMCID: PMC5802178.

15: Lee SY, Choi HC, Choe YJ, Shin SJ, Lee SH, Kim HS. Nutlin-3 induces BCL2A1 expression by activating ELK1 through the mitochondrial p53-ROS-ERK1/2 pathway. Int J Oncol. 2014 Aug;45(2):675-82. doi: 10.3892/ijo.2014.2463. Epub 2014 May 26. PMID: 24867259.

16: Voon YL, Ahmad M, Wong PF, Husaini R, Ng WT, Leong CO, Lane DP, Khoo AS. Nutlin-3 sensitizes nasopharyngeal carcinoma cells to cisplatin-induced cytotoxicity. Oncol Rep. 2015 Oct;34(4):1692-700. doi: 10.3892/or.2015.4177. Epub 2015 Aug 5. PMID: 26252575; PMCID: PMC4564086.

17: Guo Y, Li Y, Xiang B, Huang XO, Ma HB, Wang FF, Gong YP. Nutlin-3 plus tanshinone IIA exhibits synergetic anti-leukemia effect with imatinib by reactivating p53 and inhibiting the AKT/mTOR pathway in Ph+ ALL. Biochem J. 2017 Dec 6;474(24):4153-4170. doi: 10.1042/BCJ20170386. PMID: 29046392.

18: Chen H, Xue L, Huang H, Wang H, Zhang X, Zhu W, Wang Z, Wang Z, Wu H. Synergistic effect of Nutlin-3 combined with MG-132 on schwannoma cells through restoration of merlin and p53 tumour suppressors. EBioMedicine. 2018 Oct;36:252-265. doi: 10.1016/j.ebiom.2018.09.042. Epub 2018 Sep 28. PMID: 30274821; PMCID: PMC6197711.

19: Choe YJ, Lee SY, Ko KW, Shin SJ, Kim HS. Nutlin-3 induces HO-1 expression by activating JNK in a transcription-independent manner of p53. Int J Oncol. 2014 Mar;44(3):761-8. doi: 10.3892/ijo.2013.2227. Epub 2013 Dec 23. PMID: 24366007.

20: Vatsyayan R, Singhal J, Nagaprashantha LD, Awasthi S, Singhal SS. Nutlin-3 enhances sorafenib efficacy in renal cell carcinoma. Mol Carcinog. 2013 Jan;52(1):39-48. doi: 10.1002/mc.20875. Epub 2011 Oct 17. PMID: 22006587; PMCID: PMC4153352.



Additional Information

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).