CVT-313 | CAS#199986-75-9 | CDK2 inhibitor

CVT-313
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WARNING: This product is for research use only, not for human or veterinary use.

MedKoo CAT#: 406724

CAS#: 199986-75-9

Description: 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.

Chemical Structure

CVT-313

CAS# 199986-75-9

Product data Instruction

Theoretical Analysis

MedKoo Cat#: 406724
Name: CVT-313
CAS#: 199986-75-9
Chemical Formula: C20H28N6O3
Exact Mass: 400.22
Molecular Weight: 400.483
Elemental Analysis: C, 59.98; H, 7.05; N, 20.99; O, 11.98

Price and Availability

Size	Price	Availability
5mg	USD 90	Ready to ship
10mg	USD 150	Ready to ship
25mg	USD 250	Ready to ship
50mg	USD 450	Ready to ship
100mg	USD 750	Ready to ship
200mg	USD 1250	Ready to ship
500mg	USD 2050	Ready to ship
Bulk inquiry Welcome, Customer: Please do not inquire quote if your intended use is for a patient since our products are for research use and for chemical synthesis use, not for human use . For in-stock products, we listed price in the web page. You may inquire prices for which sizes were not listed. If no price is listed, this means the product is not in stock at the moment, which may be available via custom synthesis. For cost-effective reason, minimum order of 1g is requested (typically very expensive). The lead time is usually 2-4 months. Quote of less than 1g will not be provided. MedKoo may not offer quote for below reasons: (1) current available synthetic method appears to be extremely expensive which is obviously not affordable to most customers; (2) Key raw material to make the product is temporally not available; (3) DEA controlled substances; (4) the product is under patent protection in customer’s country.

Synonym: CVT-313; CVT 313; CVT313.

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

InChi Key: NQVIIUBWMBHLOZ-UHFFFAOYSA-N

InChi Code: 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)

SMILES Code: CC(C)N1C=NC2=C1N=C(N=C2NCC3=CC=C(C=C3)OC)N(CCO)CCO

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:

Product Data

Certificate of Analysis:

View CoA: current batch, Lot#CRB70411

QC Data:

View QC data: current batch, Lot#CRB70411

Safety Data Sheet (SDS):

View Safety Data Sheet (SDS)

Instruction:

View handling instruction

Biological target:	CVT-313 is an inhibitor of CDK2 with an IC50 of 0.5 μM.
In vitro activity:	Using normal and tumor human/murine cell lines, the effects of CVT-313 on cell proliferation was measured (Fig. 4 and Table I). The IC50 for growth inhibition ranged from 1.25 to 20 μm. To examine whether the growth inhibition by CVT-313 was cell cycle-specific, MRC-5 cells (human diploid lung fibroblasts) were exposed to CVT-313. After 18 h of serum stimulation, a relatively large proportion of the cells progressed into S phase, with their DNA content intermediate between 2 and 4 n. (Fig. 5 C). If CVT-313 (12.5 μm) was added to cells 18 h after serum stimulation, the DNA content of most of the cells was either 2 or 4 n with very few cells (less than 10%) entering S phase (Fig. 5, D versus C). If under similar culture conditions the concentration of CVT-313 was decreased to 6.25 μm, FACS analysis showed most cells with 2 n DNA, fewer cells with 4 n DNA, and very few cells in S phase. These data suggest that cells arrest at the G1/S and G2/M boundary at a higher concentration of CVT-313, but at the lower concentration of CVT-313, most of the cells are arrested at the G1/S boundary. Reference: J Biol Chem. 1997 Nov 14;272(46):29207-11. https://www.jbc.org/article/S0021-9258(18)50875-9/fulltext
In vivo activity:	To test the in vivo efficacy of CVT-313, an injured rat carotid artery model of restenosis was used. Exposure of the denuded carotid artery to CVT-313 (1.25 mg/kg) reduced neointima formation by 80% (Fig. 7). Moreover, in each individual animal treated with CVT-313 there was at least 70% inhibition of the neointimal area, demonstrating efficacy in every treated animal. Two lower doses of CVT-313 (0.75 and 0.25 mg/kg) were less efficacious, reducing mean neointimal area by about 30%, whereas the lowest dose tested (0.025 mg/kg) did not achieve any significant reduction in neointimal area. Reference: J Biol Chem. 1997 Nov 14;272(46):29207-11. https://www.jbc.org/article/S0021-9258(18)50875-9/fulltext

Solubility Data

	Solvent	Max Conc. mg/mL	Max Conc. mM
Solubility
	Ethanol	45.0	112.42
	DMF	20.0	49.94
	DMSO	60.0	149.85
	DMSO:PBS (pH 7.2) (1:4)	0.2	0.50

Preparing Stock Solutions

The following data is based on the product molecular weight 400.48 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. Brooks EE, Gray NS, Joly A, Kerwar SS, Lum R, Mackman RL, Norman TC, Rosete J, Rowe M, Schow SR, Schultz PG, Wang X, Wick MM, Shiffman D. CVT-313, a specific and potent inhibitor of CDK2 that prevents neointimal proliferation. J Biol Chem. 1997 Nov 14;272(46):29207-11. doi: 10.1074/jbc.272.46.29207. PMID: 9360999.
In vitro protocol:	1. Brooks EE, Gray NS, Joly A, Kerwar SS, Lum R, Mackman RL, Norman TC, Rosete J, Rowe M, Schow SR, Schultz PG, Wang X, Wick MM, Shiffman D. CVT-313, a specific and potent inhibitor of CDK2 that prevents neointimal proliferation. J Biol Chem. 1997 Nov 14;272(46):29207-11. doi: 10.1074/jbc.272.46.29207. PMID: 9360999.
In vivo protocol:	1. Brooks EE, Gray NS, Joly A, Kerwar SS, Lum R, Mackman RL, Norman TC, Rosete J, Rowe M, Schow SR, Schultz PG, Wang X, Wick MM, Shiffman D. CVT-313, a specific and potent inhibitor of CDK2 that prevents neointimal proliferation. J Biol Chem. 1997 Nov 14;272(46):29207-11. doi: 10.1074/jbc.272.46.29207. PMID: 9360999.

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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.

4: Gräub R, Lancero H, Pedersen A, Chu M, Padmanabhan K, Xu XQ, Spitz P, Chalkley R, Burlingame AL, Stokoe D, Bernstein HS. Cell cycle-dependent phosphorylation of human CDC5 regulates RNA processing. Cell Cycle. 2008 Jun 15;7(12):1795-803. Epub 2008 Jun 25. PubMed PMID: 18583928; PubMed Central PMCID: PMC2940709.

5: Deterding LJ, Bunger MK, Banks GC, Tomer KB, Archer TK. Global changes in and characterization of specific sites of phosphorylation in mouse and human histone H1 Isoforms upon CDK inhibitor treatment using mass spectrometry. J Proteome Res. 2008 Jun;7(6):2368-79. doi: 10.1021/pr700790a. Epub 2008 Apr 17. PubMed PMID: 18416567; PubMed Central PMCID: PMC2761089.

6: Faber AC, Chiles TC. Inhibition of cyclin-dependent kinase-2 induces apoptosis in human diffuse large B-cell lymphomas. Cell Cycle. 2007 Dec 1;6(23):2982-9. PubMed PMID: 18156799.

7: Bhattacharjee RN, Banks GC, Trotter KW, Lee HL, Archer TK. Histone H1 phosphorylation by Cdk2 selectively modulates mouse mammary tumor virus transcription through chromatin remodeling. Mol Cell Biol. 2001 Aug;21(16):5417-25. PubMed PMID: 11463824; PubMed Central PMCID: PMC87264.

8: Sriram V, Patterson C. Cell cycle in vasculoproliferative diseases: potential interventions and routes of delivery. Circulation. 2001 May 15;103(19):2414-9. Review. PubMed PMID: 11352893.

9: Gray N, Détivaud L, Doerig C, Meijer L. ATP-site directed inhibitors of cyclin-dependent kinases. Curr Med Chem. 1999 Sep;6(9):859-75. Review. PubMed PMID: 10495356.

10: Brooks EE, Gray NS, Joly A, Kerwar SS, Lum R, Mackman RL, Norman TC, Rosete J, Rowe M, Schow SR, Schultz PG, Wang X, Wick MM, Shiffman D. CVT-313, a specific and potent inhibitor of CDK2 that prevents neointimal proliferation. J Biol Chem. 1997 Nov 14;272(46):29207-11. PubMed PMID: 9360999.

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