CVT-313

CVT-313 is a potent and selective inhibitor of CDK2 that prevents neointimal proliferation. CVT-313 has an IC50 of 0.5 microM in vitro. Inhibition was competitive with respect to ATP (Ki = 95 nM), and selective CVT-313 had no effect on other, nonrelated ATP-dependent serine/threonine kinases. The growth of mouse, rat, and human cells in culture was also inhibited by CVT-313 with the IC50 for growth arrest ranging from 1.25 to 20 microM. CVT-313 is a promising candidate for evaluation in other disease models related to aberrant cell proliferation.

Product information

CAS Number: 199986-75-9

Molecular Weight: 400.47

Formula: C20H28N6O3

Synonym:

CVT 313

CVT313

CVT-313

Chemical Name: 2,2'-((9-isopropyl-6-((4-methoxybenzyl)amino)-9H-purin-2-yl)azanediyl)bis(ethan-1-ol)

Smiles: COC1C=CC(CNC2=NC(=NC3=C2N=CN3C(C)C)N(CCO)CCO)=CC=1

InChiKey: NQVIIUBWMBHLOZ-UHFFFAOYSA-N

InChi: InChI=1S/C20H28N6O3/c1-14(2)26-13-22-17-18(21-12-15-4-6-16(29-3)7-5-15)23-20(24-19(17)26)25(8-10-27)9-11-28/h4-7,13-14,27-28H,8-12H2,1-3H3,(H,21,23,24)

Technical Data

Appearance: Solid Power

Purity: ≥98% (or refer to the Certificate of Analysis)

Solubility: Soluble in DMSO, not in water

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical or refer to Certificate of Analysis

Storage Condition: Dry, dark and -20 ^oC for 1 year or refer to the Certificate of Analysis.

Shelf Life: ≥12 months if stored properly.

Stock Solution Storage: 0 - 4 ^oC for 1 month or refer to the Certificate of Analysis.

Drug Formulation: To be determined.

HS Tariff Code: 382200

How to use

In Vitro:

CVT-313 (Cdk2 Inhibitor III) has been shown to inhibit other kinases, but at much higher IC50 values, i.e., CDK1 (IC50=4.2 μM), CDK4 D1 (IC50=215 μM), and MAPK/PKA/PKC (IC50>1.25 mM), compared to CDK2 (IC50=0.5 μM). CVT-313 has been shown to have profound effects on cell proliferation at concentrations of 5-20 μM. CVT-313 is a potent CDK2 inhibitor, which is identified from a purine analog library with an IC50 of 0.5 μM in vitro. Inhibition is competitive with respect to ATP (Ki=95 nM), and selective CVT-313 has no effect on other, nonrelated ATP-dependent serine/threonine kinases. When added to CDK1 or CDK4, a 8.5- and 430-fold higher concentration of CVT-313 is required for half-maximal inhibition of the enzyme activity. Using normal and tumor human/murine cell lines, the effects of CVT-313 on cell proliferation is measured. The IC50 for growth inhibition ranged from 1.25 to 20 μM.

References:

1. Sakurikar N, Eastman A. Critical reanalysis of the methods that discriminate the activity of CDK2 from CDK1. Cell Cycle. 2016 May 2;15(9):1184-8. doi: 10.1080/15384101.2016.1160983. Epub 2016 Mar 17. PubMed PMID: 26986210.
2. Dong P, Maddali MV, Srimani JK, Thélot F, Nevins JR, Mathey-Prevot B, You L. Division of labour between Myc and G1 cyclins in cell cycle commitment and pace control. Nat Commun. 2014 Sep 1;5:4750. doi: 10.1038/ncomms5750. PubMed PMID: 25175461; PubMed Central PMCID: PMC4164785.
3. Hwang CY, Lee SM, Park SS, Kwon KS. CDK2 differentially controls normal cell senescence and cancer cell proliferation upon exposure to reactive oxygen species. Biochem Biophys Res Commun. 2012 Aug 17;425(1):94-9. doi: 10.1016/j.bbrc.2012.07.059. Epub 2012 Jul 20. PubMed PMID: 22819841.

Products are for research use only. Not for human use.