NU6027
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MedKoo CAT#: 406385

CAS#: 220036-08-8

Description: NU6027 is a potent inhibitor of cellular ATR activity (IC(50)=6.7 μM) and enhanced hydroxyurea and cisplatin cytotoxicity in an ATR-dependent manner. NU6027 attenuated G2/M arrest following DNA damage, inhibited RAD51 focus formation and increased the cytotoxicity of the major classes of DNA-damaging anticancer cytotoxic therapy but not the antimitotic, paclitaxel. In A2780 cells sensitisation to cisplatin was greatest in cells with functional p53 and mismatch repair (MMR) and sensitisation to temozolomide was greatest in p53 mutant cells with functional MMR. Importantly, NU6027 was synthetically lethal when DNA single-strand break repair is impaired either through poly(ADP-ribose) polymerase (PARP) inhibition or defects in XRCC1. NU6027 inhibits ATR, impairing G2/M arrest and homologous recombination thus increasing sensitivity to DNA-damaging agents and PARP inhibitors. It provides proof of concept data for clinical development of ATR inhibitors.


Chemical Structure

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NU6027
CAS# 220036-08-8

Theoretical Analysis

MedKoo Cat#: 406385
Name: NU6027
CAS#: 220036-08-8
Chemical Formula: C11H17N5O2
Exact Mass: 251.14
Molecular Weight: 251.290
Elemental Analysis: C, 52.58; H, 6.82; N, 27.87; O, 12.73

Price and Availability

Size Price Availability Quantity
5mg USD 220
10mg USD 360
50mg USD 890
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Synonym: NU6027; NU-6027; NU 6027.

IUPAC/Chemical Name: 6-(cyclohexylmethoxy)-5-nitrosopyrimidine-2,4-diamine

InChi Key: DGWXOLHKVGDQLN-UHFFFAOYSA-N

InChi Code: InChI=1S/C11H17N5O2/c12-9-8(16-17)10(15-11(13)14-9)18-6-7-4-2-1-3-5-7/h7H,1-6H2,(H4,12,13,14,15)

SMILES Code: NC1=NC(OCC2CCCCC2)=C(N=O)C(N)=N1

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:         

Product Data:
Biological target: NU6027 is a potent and ATP-competitive inhibitor of both CDK1 and CDK2, with Kis of 2.5 µM and 1.3 µM.
In vitro activity: NU6027 is a potent inhibitor of cellular ATR activity (IC(50)=6.7 μM) and enhanced hydroxyurea and cisplatin cytotoxicity in an ATR-dependent manner. NU6027 attenuated G2/M arrest following DNA damage, inhibited RAD51 focus formation and increased the cytotoxicity of the major classes of DNA-damaging anticancer cytotoxic therapy but not the antimitotic, paclitaxel. Importantly, NU6027 was synthetically lethal when DNA single-strand break repair is impaired either through poly(ADP-ribose) polymerase (PARP) inhibition or defects in XRCC1. Reference: Br J Cancer. 2011 Jul 26;105(3):372-81. https://pubmed.ncbi.nlm.nih.gov/21730979/
In vivo activity: After the TBI, this study immediately injected NU6027 (1 mg/kg, intraperitoneal), TRPC5 inhibitor, and then sacrificed rats 24 h later. This study conducted Fluoro-Jade B (FJB) staining to confirm the presence of degenerating neurons in the hippocampal cornus ammonis 3 (CA3). After the TBI, the degenerating neuronal cell count was decreased in the NU6027-treated group compared with the vehicle-treated group. Reference: Int J Mol Sci. 2020 Nov 4;21(21):8256. https://pubmed.ncbi.nlm.nih.gov/33158109/

Solubility Data

Solvent Max Conc. mg/mL Max Conc. mM
Solubility
DMF 5.0 19.90
DMSO 24.2 96.17
DMSO:PBS (pH 7.2) (1:2) 0.3 1.19
Ethanol 2.0 7.96

Preparing Stock Solutions

The following data is based on the product molecular weight 251.29 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
Formulation protocol: 1. Peasland A, Wang LZ, Rowling E, Kyle S, Chen T, Hopkins A, Cliby WA, Sarkaria J, Beale G, Edmondson RJ, Curtin NJ. Identification and evaluation of a potent novel ATR inhibitor, NU6027, in breast and ovarian cancer cell lines. Br J Cancer. 2011 Jul 26;105(3):372-81. doi: 10.1038/bjc.2011.243. Epub 2011 Jul 5. PMID: 21730979; PMCID: PMC3172902. 2. Arris CE, Boyle FT, Calvert AH, Curtin NJ, Endicott JA, Garman EF, Gibson AE, Golding BT, Grant S, Griffin RJ, Jewsbury P, Johnson LN, Lawrie AM, Newell DR, Noble ME, Sausville EA, Schultz R, Yu W. Identification of novel purine and pyrimidine cyclin-dependent kinase inhibitors with distinct molecular interactions and tumor cell growth inhibition profiles. J Med Chem. 2000 Jul 27;43(15):2797-804. doi: 10.1021/jm990628o. PMID: 10956187. 3. Park MK, Choi BY, Kho AR, Lee SH, Hong DK, Jeong JH, Kang DH, Kang BS, Suh SW. Effects of Transient Receptor Potential Cation 5 (TRPC5) Inhibitor, NU6027, on Hippocampal Neuronal Death after Traumatic Brain Injury. Int J Mol Sci. 2020 Nov 4;21(21):8256. doi: 10.3390/ijms21218256. PMID: 33158109; PMCID: PMC7662546.
In vitro protocol: 1. Peasland A, Wang LZ, Rowling E, Kyle S, Chen T, Hopkins A, Cliby WA, Sarkaria J, Beale G, Edmondson RJ, Curtin NJ. Identification and evaluation of a potent novel ATR inhibitor, NU6027, in breast and ovarian cancer cell lines. Br J Cancer. 2011 Jul 26;105(3):372-81. doi: 10.1038/bjc.2011.243. Epub 2011 Jul 5. PMID: 21730979; PMCID: PMC3172902. 2. Arris CE, Boyle FT, Calvert AH, Curtin NJ, Endicott JA, Garman EF, Gibson AE, Golding BT, Grant S, Griffin RJ, Jewsbury P, Johnson LN, Lawrie AM, Newell DR, Noble ME, Sausville EA, Schultz R, Yu W. Identification of novel purine and pyrimidine cyclin-dependent kinase inhibitors with distinct molecular interactions and tumor cell growth inhibition profiles. J Med Chem. 2000 Jul 27;43(15):2797-804. doi: 10.1021/jm990628o. PMID: 10956187.
In vivo protocol: 1. Park MK, Choi BY, Kho AR, Lee SH, Hong DK, Jeong JH, Kang DH, Kang BS, Suh SW. Effects of Transient Receptor Potential Cation 5 (TRPC5) Inhibitor, NU6027, on Hippocampal Neuronal Death after Traumatic Brain Injury. Int J Mol Sci. 2020 Nov 4;21(21):8256. doi: 10.3390/ijms21218256. PMID: 33158109; PMCID: PMC7662546.

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1: Peasland A, Wang LZ, Rowling E, Kyle S, Chen T, Hopkins A, Cliby WA, Sarkaria J, Beale G, Edmondson RJ, Curtin NJ. Identification and evaluation of a potent novel ATR inhibitor, NU6027, in breast and ovarian cancer cell lines. Br J Cancer. 2011 Jul 26;105(3):372-81. doi: 10.1038/bjc.2011.243. Epub 2011 Jul 5. PubMed PMID: 21730979; PubMed Central PMCID: PMC3172902.

2: 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.

3: Mesguiche V, Parsons RJ, Arris CE, Bentley J, Boyle FT, Curtin NJ, Davies TG, Endicott JA, Gibson AE, Golding BT, Griffin RJ, Jewsbury P, Johnson LN, Newell DR, Noble ME, Wang LZ, Hardcastle IR. 4-Alkoxy-2,6-diaminopyrimidine derivatives: inhibitors of cyclin dependent kinases 1 and 2. Bioorg Med Chem Lett. 2003 Jan 20;13(2):217-22. PubMed PMID: 12482427.