Nutlin-3 | CAS# 548472-68-0

MedKoo Cat#: 471022 | Name: Nutlin-3

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Description:

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

Nutlin-3, also known as (±)-Nutlin-3 and N-6287, is a p53-Mdm2 Antagonist for Nasopharyngeal Carcinoma Treatment. Nutlin-3 specifically targets p53-Mdm2 interaction offers new therapeutic opportunities by enhancing cancer cell growth arrest and apoptosis through the restoration of the p53-mediated tumor suppression pathway while producing minimal cytotoxicity and side effects. Nutlin-3 reverses the epithelial-mesenchymal transition in gemcitabine-resistant hepatocellular carcinoma cells. Nutlin-3 sensitizes nasopharyngeal carcinoma cells to cisplatin-induced cytotoxicity.

Chemical Structure

Nutlin-3

CAS#548472-68-0 (4R5S and 4S5R)

Theoretical Analysis

MedKoo Cat#: 471022

Name: Nutlin-3

CAS#: 548472-68-0 (4R5S and 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	Quantity
100mg	USD 750.00
200mg	USD 1,350.00
500mg	USD 2,150.00
1g	USD 3,250.00
2g	USD 4,650.00
5g	USD 6,950.00

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Related CAS #

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

Synonym

(±)-Nutlin-3, Nutlin-3, Nutlin 3; N 6287; N-6287; N6287;

IUPAC/Chemical Name

(±)-4-[4,5-bis-(4-chlorophenyl)-2-(2-isopropoxy-4-methoxy-phenyl)-4,5-dihydro-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

ClC1=CC=C([C@H]2[C@H](N(C(C3=CC=C(C=C3OC(C)C)OC)=N2)C(N4CCN(C(C4)=O)[H])=O)C5=CC=C(C=C5)Cl)C=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

Shelf Life

>3 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

Product Data

Product Data

Instruction

View handling instruction

Biological target:

Nutlin-3 is a commercial available p53-MDM2 inhibitor, with Ki of 90 nM.

In vitro activity:

As a single agent, Nutlin-3 (2-10 micromol/L) stabilized p53 and p21(WAF) levels and was toxic to WTp53-22RV1 cells (IC(50), 4.3 micromol/L) but had minimal toxicity toward p53-deficient cells (IC(50), >10 micromol/L). When combined with radiation under oxic conditions, Nutlin-3 decreased clonogenic survival in all three cell lines: 22RV1 [sensitizing enhancement ratio (SER), 1.24], DU145 (SER, 1.27), and PC-3 (SER, 1.12). Anoxia induced p53 protein expression in 22RV1 cells and this was augmented by Nutlin-3 treatment. Furthermore, Nutlin-3 was more effective as a radiosensitizer under hypoxic conditions particularly in WTp53-expressing cells: 22RV1 (SER, 1.78), DU145 (SER, 1.31), and PC-3 (SER, 1.28). Reference: Mol Cancer Ther. 2008 Apr;7(4):993-9. https://pubmed.ncbi.nlm.nih.gov/18413812/

In vivo activity:

Nutlin-3 inhibits clonogenic growth of ESCC cells and exerts a synergistic cytotoxic-effect when combined with chemotherapeutic agent cisplatin. Moreover, xenograft tumor growth in SCID mice was suppressed by Nutlin-3. The protein expression level of DNMTs was downregulated, and that of TSGs was upregulated by Nutlin-3 treatment in the excised tumor tissue. Reference: Mol Carcinog. 2023 Feb;62(2):277-287. https://pubmed.ncbi.nlm.nih.gov/36342355/

	Solvent	mg/mL	mM
Solubility
	DMF	30.0	51.59
	DMSO	44.4	76.33
	Ethanol	61.1	104.99
	Ethanol:PBS (pH 7.2) (1:10)	0.1	0.17

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:

1. Zheng K, Li Z, Ding X, Li H. Nutlin-3 suppresses tumorigenesis and progression of oral squamous cell carcinoma and enhances chemosensitivity to cisplatin. Cytotechnology. 2023 Feb;75(1):17-25. doi: 10.1007/s10616-022-00556-w. Epub 2022 Oct 28. PMID: 36713063; PMCID: PMC9880094. 2. Supiot S, Hill RP, Bristow RG. Nutlin-3 radiosensitizes hypoxic prostate cancer cells independent of p53. Mol Cancer Ther. 2008 Apr;7(4):993-9. doi: 10.1158/1535-7163.MCT-07-0442. PMID: 18413812. 3. Chang WL, Hsieh CH, Kuo IY, Lin CH, Huang YL, Wang YC. Nutlin-3 acts as a DNA methyltransferase inhibitor to sensitize esophageal cancer to chemoradiation. Mol Carcinog. 2023 Feb;62(2):277-287. doi: 10.1002/mc.23485. Epub 2022 Nov 7. PMID: 36342355. 4. Stine KC, Wahl EC, Liu L, Skinner RA, VanderSchilden J, Bunn RC, Montgomery CO, Aronson J, Becton DL, Nicholas RW, Swearingen CJ, Suva LJ, Lumpkin CK. Nutlin-3 treatment spares cisplatin-induced inhibition of bone healing while maintaining osteosarcoma toxicity. J Orthop Res. 2016 Oct;34(10):1716-1724. doi: 10.1002/jor.23192. Epub 2016 Feb 26. PMID: 26867804; PMCID: PMC5516939.

In vitro protocol:

In vivo protocol:

1. Chang WL, Hsieh CH, Kuo IY, Lin CH, Huang YL, Wang YC. Nutlin-3 acts as a DNA methyltransferase inhibitor to sensitize esophageal cancer to chemoradiation. Mol Carcinog. 2023 Feb;62(2):277-287. doi: 10.1002/mc.23485. Epub 2022 Nov 7. PMID: 36342355. 2. Stine KC, Wahl EC, Liu L, Skinner RA, VanderSchilden J, Bunn RC, Montgomery CO, Aronson J, Becton DL, Nicholas RW, Swearingen CJ, Suva LJ, Lumpkin CK. Nutlin-3 treatment spares cisplatin-induced inhibition of bone healing while maintaining osteosarcoma toxicity. J Orthop Res. 2016 Oct;34(10):1716-1724. doi: 10.1002/jor.23192. Epub 2016 Feb 26. PMID: 26867804; PMCID: PMC5516939.

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.