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Contributor Information

  • Name Roger Griffin
  • Institute Newcastle University

Tool Details

  • Tool name: CDK2 inhibitor NU6301 Small Molecule (Tool Compound)
  • Molecular formula: C18H21N6O4S1(CH3)- K+
  • Tool type: Small molecules
  • Tool sub-type: Inhibitor
  • Purpose: Inhibitor
  • Application: The prodrug NU6301 rapidly generated NU6102 in vitro in mouse plasma, and tumour NU6102 levels in vivo consistent with activity in vitro. Eight or 12 hourly dosing of 120 mg/kg NU6301 for 10 days was well tolerated in SKUT-1B tumour-bearing mice and inhibited Rb phosphorylation in tumour tissue. Two (8 hourly dosing) and 3 (12 hourly dosing) day tumour growth delay was observed (p=0.04 and p=0.007, respectively) following NU6301 administration. NU6102 selectively inhibited the growth of CDK2 WT (wild type) versus KO MEFs (knockout mouse embryo fibroblasts) (GI₅₀ (concentration required to inhibit cell growth by 50%) 14 ÎźM versus >30 ÎźM), and was more growth-inhibitory in p53 mutant or null versus p53 WT cells (p=0.02), and in Rb (retinoblastoma protein) WT SKUT-1B versus SKUT 1 Rb deficient cells (p=0.01). In SKUT-1B cells NU6102 induced a G2 arrest, inhibition of Rb phosphorylation and cytotoxicity (LC₅₀ 2.6 ÎźM for a 24h exposure).
  • Description: The CDK2 inhibitor NU6301 is a water soluble prodrug of NU6102, a potent CDK1/cyclin B and CDK2/cyclin A3 inhibitor (IC50 values are 9.5 and 5.4 nM for CDK1/cyclin B and CDK2/cyclin A3 respectively). CDK2 is a member of a family of serine/threonine protein kinases that participate in cell cycle regulation. CDK2 is the catalytic subunit of the cyclin-dependent protein kinase complex, which regulates progression through the cell cycle. Activity of this protein is especially critical during the G1 to S phase transition. CDK2 associates with and regulated by other subunits of the complex including cyclin A or E, CDK inhibitor p21Cip1 (CDKN1A), and p27Kip1 (CDKN1B).
  • Research area: Cancer
  • IUPAC: N-Acetyl-4-(6-cyclohexylmethoxy-9H-purin-2-ylamino)-benzenesulfonamide potassium salt

  • For Research Use Only

Target Details

  • Primary target: Cyclin dependent kinase 2 (CDK2)

Application Details

  • Application: The prodrug NU6301 rapidly generated NU6102 in vitro in mouse plasma, and tumour NU6102 levels in vivo consistent with activity in vitro. Eight or 12 hourly dosing of 120 mg/kg NU6301 for 10 days was well tolerated in SKUT-1B tumour-bearing mice and inhibited Rb phosphorylation in tumour tissue. Two (8 hourly dosing) and 3 (12 hourly dosing) day tumour growth delay was observed (p=0.04 and p=0.007, respectively) following NU6301 administration. NU6102 selectively inhibited the growth of CDK2 WT (wild type) versus KO MEFs (knockout mouse embryo fibroblasts) (GI₅₀ (concentration required to inhibit cell growth by 50%) 14 ÎźM versus >30 ÎźM), and was more growth-inhibitory in p53 mutant or null versus p53 WT cells (p=0.02), and in Rb (retinoblastoma protein) WT SKUT-1B versus SKUT 1 Rb deficient cells (p=0.01). In SKUT-1B cells NU6102 induced a G2 arrest, inhibition of Rb phosphorylation and cytotoxicity (LC₅₀ 2.6 ÎźM for a 24h exposure).

Handling

  • Purity:
  • Shipping conditions: Dry Ice

Documentation

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References

  • •  Thomas, H et al
  • •  European Journal of Cancer, Volume 47, Issue 13, September 2011, Pages 2052–2059