2vu3

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.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.

Structural highlights 2vu3 is a 1 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: Related: 1pye, 1h08, 2vth, 2b53, 1v1k, 1okv, 1ke7, 1h25, 1pxk, 2bhh, 2vta, 2uue, 1gz8, 1e1v, 1ol2, 1h27, 1jsv, 2b52, 1ke5, 1fin, 2c5o, 2c68, 2vtt, 1p2a, 2vtq, 2c4g, 1w0x, 1h1q, 1pxo, 1ke9, 2a0c, 1hck, 1jsu, 1pxn, 2uze, 2vtm, 2v0d, 1oiq, 1h1r, 2iw8, 1gih, 1hcl, 1pw2, 2vtn, 1jst, 1oiu, 1pxm, 1b38, 1fq1, 1vyw, 1h1p, 2c69, 1urc, 1pxi, 2c6i, 1ykr, 2uzd, 2c6k, 2c5y, 1wcc, 2j9m, 1vyz, 2vti, 1jvp, 1w98, 1pkd, 1p5e, 2vts, 2c5p, 2uzn, 2b54, 1ke6, 1pxj, 2uzl, 2cci, 2bkz, 2g9x, 1y91, 2iw6, 1gij, 1r78, 1h0v, 2iw9, 1w8c, 1buh, 2bpm, 2bts, 1fvv, 1okw, 2vtp, 2a4l, 2c6t, 1fvt, 1qmz, 1ogu, 2b55, 1pf8, 1h1s, 2c5v, 2jgz, 2bhe, 1urw, 1oiy, 2c6l, 1f5q, 2c6o, 2vtl, 1ol1, 1h01, 2uzb, 1oir, 1oi9, 2vtj, 2cjm, 2c5n, 2c5x, 2c6m, 1oit, 2v22, 1gy3, 1gii, 1di8, 1e9h, 2vto, 1dm2, 2uzo, 1h24, 1h00, 2exm, 2clx, 1pxp, 2cch, 1b39, 2btr, 1aq1, 1h0w, 1g5s, 1ckp, 1ke8, 1h28, 1pxl, 2vtr, 1h26, 1e1x, 1h07, 1y8y Resources: FirstGlance, OCA, RCSB, PDBsum Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMed The application of fragment-based screening techniques to cyclin dependent kinase 2 (CDK2) identified multiple (>30) efficient, synthetically tractable small molecule hits for further optimization. Structure-based design approaches led to the identification of multiple lead series, which retained the key interactions of the initial binding fragments and additionally explored other areas of the ATP binding site. The majority of this paper details the structure-guided optimization of indazole (6) using information gained from multiple ligand-CDK2 cocrystal structures. Identification of key binding features for this class of compounds resulted in a series of molecules with low nM affinity for CDK2. Optimisation of cellular activity and characterization of pharmacokinetic properties led to the identification of 33 (AT7519), which is currently being evaluated in clinical trials for the treatment of human cancers. 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.,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 J Med Chem. 2008 Aug 28;51(16):4986-99. Epub 2008 Jul 26. PMID:18656911 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Cell division protein kinase 2

spinqualitylabelsall models 2vu3, resolution 1.85Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image