CDK2 inhibitor NU6301 Small Molecule (Tool Compound)
Invented at University of Newcastle upon Tyne
- Datasheet
- References (2)
- Inventor Info
Info
| Catalogue Number | 152754 |
| Antigen/Gene or Protein Targets | Cyclin dependent kinase 2 (CDK2) |
| Type | Inhibitor |
| Relevance | 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). |
| Molecular Formula | C18H21N6O4S1(CH3)- K+ |
| lUPAC | N-Acetyl-4-(6-cyclohexylmethoxy-9H-purin-2-ylamino)-benzenesulfonamide potassium salt |
| In vivo applications | 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. |
| In vitro applications | 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 μM versus >30 μM), 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 μM for a 24h exposure). |
| Research Area | Cancer, Cell Cycle |
References: 2 entries
Thomas et al. 2011. Eur J Cancer. 47(13):2052-9. PMID: 21570822.
Preclinical in vitro and in vivo evaluation of the potent and specific cyclin-dependent kinase 2 inhibitor NU6102 and a water soluble prodrug NU6301.
Europe PMC ID: 21570822
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References: 2 entries
Thomas et al. 2011. Eur J Cancer. 47(13):2052-9. PMID: 21570822.
Preclinical in vitro and in vivo evaluation of the potent and specific cyclin-dependent kinase 2 inhibitor NU6102 and a water soluble prodrug NU6301.
Add a reference
