Related CAS #: 902135-91-5 (HCl)   844442-38-2 (free base)   .  

Synonym: AT7519; AT-7519; AT 7519; AT-7519 HCl.

IUPAC/Chemical Name: N-(4-Piperidinyl)-4-(2,6-dichlorobenzoylamino)-1H-pyrazole-3-carboxamide hydrochloride

InChi Key: PAOFPNGYBWGKCO-UHFFFAOYSA-N

InChi Code: InChI=1S/C16H17Cl2N5O2.ClH/c17-10-2-1-3-11(18)13(10)15(24)22-12-8-20-23-14(12)16(25)21-9-4-6-19-7-5-9;/h1-3,8-9,19H,4-7H2,(H,20,23)(H,21,25)(H,22,24);1H

SMILES Code: O=C(C1=NNC=C1NC(C2=C(Cl)C=CC=C2Cl)=O)NC3CCNCC3.[H]Cl

Technical Data

Additional Information

 Related:
902135-91-5 (AT-7519 HCl salt)
844442-38-2 (AT-7519 free base).

References

1: Lucas CD, Dorward DA, Tait MA, Fox S, Marwick JA, Allen KC, Robb CT, Hirani N, Haslett C, Duffin R, Rossi AG. Downregulation of Mcl-1 has anti-inflammatory pro-resolution effects and enhances bacterial clearance from the lung. Mucosal Immunol. 2013 Nov 27. doi: 10.1038/mi.2013.102. [Epub ahead of print] PubMed PMID: 24280938.

2: Dolman ME, den Hartog IJ, Molenaar JJ, Schellens JH, Beijnen JH, Sparidans RW. Liquid chromatography-tandem mass spectrometric assay for the cyclin-dependent kinase inhibitor AT7519 in mouse plasma. J Pharm Biomed Anal. 2014 Jan 25;88:216-20. doi: 10.1016/j.jpba.2013.08.051. Epub 2013 Sep 12. PubMed PMID: 24080524.

3: Alessandri AL, Duffin R, Leitch AE, Lucas CD, Sheldrake TA, Dorward DA, Hirani N, Pinho V, de Sousa LP, Teixeira MM, Lyons JF, Haslett C, Rossi AG. Induction of eosinophil apoptosis by the cyclin-dependent kinase inhibitor AT7519 promotes the resolution of eosinophil-dominant allergic inflammation. PLoS One. 2011;6(9):e25683. doi: 10.1371/journal.pone.0025683. Epub 2011 Sep 30. PubMed PMID: 21984938; PubMed Central PMCID: PMC3184151.

4: Mahadevan D, Plummer R, Squires MS, Rensvold D, Kurtin S, Pretzinger C, Dragovich T, Adams J, Lock V, Smith DM, Von Hoff D, Calvert H. A phase I pharmacokinetic and pharmacodynamic study of AT7519, a cyclin-dependent kinase inhibitor in patients with refractory solid tumors. Ann Oncol. 2011 Sep;22(9):2137-43. doi: 10.1093/annonc/mdq734. Epub 2011 Feb 16. PubMed PMID: 21325451.

5: Squires MS, Cooke L, Lock V, Qi W, Lewis EJ, Thompson NT, Lyons JF, Mahadevan D. AT7519, a cyclin-dependent kinase inhibitor, exerts its effects by transcriptional inhibition in leukemia cell lines and patient samples. Mol Cancer Ther. 2010 Apr;9(4):920-8. doi: 10.1158/1535-7163.MCT-09-1071. Epub 2010 Mar 30. PubMed PMID: 20354122.

6: Santo L, Vallet S, Hideshima T, Cirstea D, Ikeda H, Pozzi S, Patel K, Okawa Y, Gorgun G, Perrone G, Calabrese E, Yule M, Squires M, Ladetto M, Boccadoro M, Richardson PG, Munshi NC, Anderson KC, Raje N. AT7519, A novel small molecule multi-cyclin-dependent kinase inhibitor, induces apoptosis in multiple myeloma via GSK-3beta activation and RNA polymerase II inhibition. Oncogene. 2010 Apr 22;29(16):2325-36. doi: 10.1038/onc.2009.510. Epub 2010 Jan 25. PubMed PMID: 20101221; PubMed Central PMCID: PMC3183744.

7: Squires MS, Feltell RE, Wallis NG, Lewis EJ, Smith DM, Cross DM, Lyons JF, Thompson NT. Biological characterization of AT7519, a small-molecule inhibitor of cyclin-dependent kinases, in human tumor cell lines. Mol Cancer Ther. 2009 Feb;8(2):324-32. doi: 10.1158/1535-7163.MCT-08-0890. Epub 2009 Jan 27. PubMed PMID: 19174555.

8: Wyatt PG, Woodhead AJ, Berdini V, Boulstridge JA, Carr MG, Cross DM, Davis DJ, Devine LA, Early TR, Feltell RE, Lewis EJ, McMenamin RL, Navarro EF, O'Brien MA, O'Reilly M, Reule M, Saxty G, Seavers LC, Smith DM, Squires MS, Trewartha G, Walker MT, Woolford AJ. Identification of N-(4-piperidinyl)-4-(2,6-dichlorobenzoylamino)-1H-pyrazole-3-carboxamide (AT7519), a novel cyclin dependent kinase inhibitor using fragment-based X-ray crystallography and structure based drug design. J Med Chem. 2008 Aug 28;51(16):4986-99. doi: 10.1021/jm800382h. Epub 2008 Jul 26. PubMed PMID: 18656911.