NU6102 | CAS#444722-95-6 | CDK inhibitor

MedKoo Cat#: 407387 | Name: NU6102

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Description:

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

NU6102 is a potent inhibitor of Cdk1 and Cdk2 with Ki values of 9 and 6 nM and IC50 values of 9.5 and 5.4 nM, respectively. NU 6102 inhibits Cdk4 activity with an IC50 value of 1.6 μM

Chemical Structure

NU6102

CAS#444722-95-6

Theoretical Analysis

MedKoo Cat#: 407387

Name: NU6102

CAS#: 444722-95-6

Chemical Formula: C18H22N6O3S

Exact Mass: 402.1474

Molecular Weight: 402.47

Elemental Analysis: C, 53.72; H, 5.51; N, 20.88; O, 11.93; S, 7.97

Price and Availability

Size	Price	Availability	Quantity
5mg	USD 290.00	2 Weeks

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Related CAS #

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Synonym

NU6102; NU-6102; NU 6102.

IUPAC/Chemical Name

4-((6-(cyclohexylmethoxy)-9H-purin-2-yl)amino)benzenesulfonamide

InChi Key

OWXORKPNCHJYOF-UHFFFAOYSA-N

InChi Code

InChI=1S/C18H22N6O3S/c19-28(25,26)14-8-6-13(7-9-14)22-18-23-16-15(20-11-21-16)17(24-18)27-10-12-4-2-1-3-5-12/h6-9,11-12H,1-5,10H2,(H2,19,25,26)(H2,20,21,22,23,24)

SMILES Code

O=S(C1=CC=C(NC2=NC(OCC3CCCCC3)=C4N=CNC4=N2)C=C1)(N)=O

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

>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

Product Data

Product Data

Certificate of Analysis

View CoA: current batch, Lot#C8M06C14

Safety Data Sheet (SDS)

View Safety Data Sheet (SDS)

Instruction

View handling instruction

Biological target:

NU6102 is a potent CDK1 and CDK2 inhibitor with IC50s of 9.5 nM and 5.4 nM for CDK1/cyclinB and CDK2/cyclinA3, respectively.

In vitro activity:

The cellular effects of CDK2/1 siRNA knockdown and purine-based CDK2/1 inhibitors, NU2058 and NU6102, were measured in anti-estrogen-sensitive and resistant breast cancer cell lines. NU6102 was a more potent inhibitor of cell growth, with GI50 values of 5–18 μm across the panel (Supplementary Figure 2A, B and Figure 3A). Similarly, NU6102 reduced cell survival, with LC50 values ranging between 6 and 14 μm (Supplementary Figure 2C, D and Figure 3B). Exposure to 5 μm NU6102 reduced the levels of pRbpThr821 in the more sensitive LCC9 cell line (GI50∼5 μm); 15 μm NU6102 was required to detect reduced pRbThr821 phosphorylation in MCF7 (GI50∼15 μm) and MMU2 (GI50∼10 μm) cells (Figure 4A). Furthermore, when CDK1/2-depleted cells were treated with NU2058 and NU6102 and cell survival was measured, there was no further reduction in colony formation compared with CDK1/2 knockdown alone. This provides additional evidence that inhibition of CDK1 and CDK2 is the mechanism by which NU2058 and NU6102 kill breast cancer cells (Figure 6D). Br J Cancer. 2010 Jan 19; 102(2): 342–350. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2816653/

In vivo activity:

An in vivo tumour growth inhibition study was performed using the HT29 model treated for 10 days with the NU6102 prodrug NU6301 at 120 mg kg−1 twice each day (equivalent to 100 mg kg−1 NU6102), pictilisib (GDC-0941) at 100 mg kg−1 per day or the combination of the two drugs at these doses in vivo in CD-1 nude mice. As shown in Figure 4C, RTV in mice treated with the combination of NU6301 and pictilisib (GDC-0941) were significantly lower in comparison with either of the drugs alone (P=0.008 and P=0.018, respectively, Mann–Whitney test) at the end of treatment (day 10). There was no tumour growth in the combination group while on treatment, whereas single-agent treatment at the doses used only generated growth delays, which were not significant in the case of NU6301 alone (time to RTV4 vs control – P=0.13, Mann–Whitney test), and not highly significant in the case of pictilisib (GDC-0941; time to RTV4 vs control – P=0.026, Mann–Whitney test). In contrast, growth delay was highly significant for the combination therapy (time to RTV4 vs control – P=0.0043, Mann–Whitney test). These studies identified a novel series of mixed CDK2/PI3K inhibitors and demonstrate that dual targeting of CDK2 and PI3K can result in enhanced antitumour activity. Br J Cancer. 2016 Sep 6; 115(6): 682–690. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5023777/

	Solvent	mg/mL	mM
Solubility
	DMSO	1.0	2.50

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 402.47 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. Thomas HD, Wang LZ, Roche C, Bentley J, Cheng Y, Hardcastle IR, Golding BT, Griffin RJ, Curtin NJ, Newell DR. Preclinical in vitro and in vivo evaluation of the potent and specific cyclin-dependent kinase 2 inhibitor NU6102 and a water soluble prodrug NU6301. Eur J Cancer. 2011 Sep;47(13):2052-9. doi: 10.1016/j.ejca.2011.04.008. Epub 2011 May 12. PMID: 21570822. 2. Johnson N, Bentley J, Wang LZ, Newell DR, Robson CN, Shapiro GI, Curtin NJ. Pre-clinical evaluation of cyclin-dependent kinase 2 and 1 inhibition in anti-estrogen-sensitive and resistant breast cancer cells. Br J Cancer. 2010 Jan 19;102(2):342-50. doi: 10.1038/sj.bjc.6605479. Epub 2009 Dec 15. PMID: 20010939; PMCID: PMC2816653. 3. Thomas HD, Wang LZ, Roche C, Bentley J, Cheng Y, Hardcastle IR, Golding BT, Griffin RJ, Curtin NJ, Newell DR. Preclinical in vitro and in vivo evaluation of the potent and specific cyclin-dependent kinase 2 inhibitor NU6102 and a water soluble prodrug NU6301. Eur J Cancer. 2011 Sep;47(13):2052-9. doi: 10.1016/j.ejca.2011.04.008. Epub 2011 May 12. PMID: 21570822. 4. Beale G, Haagensen EJ, Thomas HD, Wang LZ, Revill CH, Payne SL, Golding BT, Hardcastle IR, Newell DR, Griffin RJ, Cano C. Combined PI3K and CDK2 inhibition induces cell death and enhances in vivo antitumour activity in colorectal cancer. Br J Cancer. 2016 Sep 6;115(6):682-90. doi: 10.1038/bjc.2016.238. Epub 2016 Aug 16. PMID: 27529512; PMCID: PMC5023777.

In vitro protocol:

In vivo protocol:

1: Beale G, Haagensen EJ, Thomas HD, Wang LZ, Revill CH, Payne SL, Golding BT, Hardcastle IR, Newell DR, Griffin RJ, Cano C. Combined PI3K and CDK2 inhibition induces cell death and enhances in vivo antitumour activity in colorectal cancer. Br J Cancer. 2016 Sep 6;115(6):682-90. doi: 10.1038/bjc.2016.238. PubMed PMID: 27529512; PubMed Central PMCID: PMC5023777. 2: Treviño LS, Bolt MJ, Grimm SL, Edwards DP, Mancini MA, Weigel NL. Differential Regulation of Progesterone Receptor-Mediated Transcription by CDK2 and DNA-PK. Mol Endocrinol. 2016 Feb;30(2):158-72. doi: 10.1210/me.2015-1144. PubMed PMID: 26652902; PubMed Central PMCID: PMC4792227. 3: Anscombe E, Meschini E, Mora-Vidal R, Martin MP, Staunton D, Geitmann M, Danielson UH, Stanley WA, Wang LZ, Reuillon T, Golding BT, Cano C, Newell DR, Noble ME, Wedge SR, Endicott JA, Griffin RJ. Identification and Characterization of an Irreversible Inhibitor of CDK2. Chem Biol. 2015 Sep 17;22(9):1159-64. doi: 10.1016/j.chembiol.2015.07.018. PubMed PMID: 26320860; PubMed Central PMCID: PMC4579270. 4: Moore NL, Edwards DP, Weigel NL. Cyclin A2 and its associated kinase activity are required for optimal induction of progesterone receptor target genes in breast cancer cells. J Steroid Biochem Mol Biol. 2014 Oct;144 Pt B:471-82. doi: 10.1016/j.jsbmb.2014.09.009. PubMed PMID: 25220500; PubMed Central PMCID: PMC4201666. 5: Thomas HD, Wang LZ, Roche C, Bentley J, Cheng Y, Hardcastle IR, Golding BT, Griffin RJ, Curtin NJ, Newell DR. Preclinical in vitro and in vivo evaluation of the potent and specific cyclin-dependent kinase 2 inhibitor NU6102 and a water soluble prodrug NU6301. Eur J Cancer. 2011 Sep;47(13):2052-9. doi: 10.1016/j.ejca.2011.04.008. PubMed PMID: 21570822. 6: Johnson N, Bentley J, Wang LZ, Newell DR, Robson CN, Shapiro GI, Curtin NJ. Pre-clinical evaluation of cyclin-dependent kinase 2 and 1 inhibition in anti-estrogen-sensitive and resistant breast cancer cells. Br J Cancer. 2010 Jan 19;102(2):342-50. doi: 10.1038/sj.bjc.6605479. PubMed PMID: 20010939; PubMed Central PMCID: PMC2816653. 7: Harrison LR, Ottley CJ, Pearson DG, Roche C, Wedge SR, Dolan ME, Newell DR, Tilby MJ. The kinase inhibitor O6-cyclohexylmethylguanine (NU2058) potentiates the cytotoxicity of cisplatin by mechanisms that are independent of its effect upon CDK2. Biochem Pharmacol. 2009 May 15;77(10):1586-92. doi: 10.1016/j.bcp.2009.02.018. PubMed PMID: 19426695. 8: Krasinska L, Cot E, Fisher D. Selective chemical inhibition as a tool to study Cdk1 and Cdk2 functions in the cell cycle. Cell Cycle. 2008 Jun 15;7(12):1702-8. PubMed PMID: 18583935; PubMed Central PMCID: PMC3804923. 9: Pratt DJ, Bentley J, Jewsbury P, Boyle FT, Endicott JA, Noble ME. Dissecting the determinants of cyclin-dependent kinase 2 and cyclin-dependent kinase 4 inhibitor selectivity. J Med Chem. 2006 Sep 7;49(18):5470-7. PubMed PMID: 16942020. 10: Heady L, Fernandez-Serra M, Mancera RL, Joyce S, Venkitaraman AR, Artacho E, Skylaris CK, Ciacchi LC, Payne MC. Novel structural features of CDK inhibition revealed by an ab initio computational method combined with dynamic simulations. J Med Chem. 2006 Aug 24;49(17):5141-53. PubMed PMID: 16913703. 11: Sheinerman FB, Giraud E, Laoui A. High affinity targets of protein kinase inhibitors have similar residues at the positions energetically important for binding. J Mol Biol. 2005 Oct 7;352(5):1134-56. PubMed PMID: 16139843. 12: Jiang Y, Zou J, Gui C. Study of a ligand complexed with Cdk2/Cdk4 by computer simulation. J Mol Model. 2005 Nov;11(6):509-15. PubMed PMID: 15928920. 13: Hardcastle IR, Arris CE, Bentley J, Boyle FT, Chen Y, Curtin NJ, Endicott JA, Gibson AE, Golding BT, Griffin RJ, Jewsbury P, Menyerol J, Mesguiche V, Newell DR, Noble ME, Pratt DJ, Wang LZ, Whitfield HJ. N2-substituted O6-cyclohexylmethylguanine derivatives: potent inhibitors of cyclin-dependent kinases 1 and 2. J Med Chem. 2004 Jul 15;47(15):3710-22. PubMed PMID: 15239650. 14: Davies TG, Bentley J, Arris CE, Boyle FT, Curtin NJ, Endicott JA, Gibson AE, Golding BT, Griffin RJ, Hardcastle IR, Jewsbury P, Johnson LN, Mesguiche V, Newell DR, Noble ME, Tucker JA, Wang L, Whitfield HJ. Structure-based design of a potent purine-based cyclin-dependent kinase inhibitor. Nat Struct Biol. 2002 Oct;9(10):745-9. PubMed PMID: 12244298.

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KSJ0001

MedKoo CAT#: 530620

CAS#: 74805-39-3