2wpa

Optimisation of 6,6-Dimethyl Pyrrolo 3,4-c pyrazoles: Identification of PHA-793887, a Potent CDK Inhibitor Suitable for Intravenous Dosing

spinqualitylabelsall models 2wpa, resolution 2.51Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 2wpa is a 4 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: 889, SO4 Related: 1pye, 1h08, 2vth, 2b53, 1v1k, 1okv, 1h25, 1ke7, 1pxk, 2wih, 2bhh, 2vta, 2uue, 1gz8, 1e1v, 1ol2, 1h27, 1jsv, 2b52, 2wha, 1ke5, 1fin, 2c5o, 2c68, 2vtt, 1p2a, 2c4g, 2vtq, 1h1q, 1w0x, 1pxo, 2w05, 1ke9, 2a0c, 1hck, 1jsu, 1pxn, 2uze, 2v0d, 2vtm, 1oiq, 1h1r, 2iw8, 1pw2, 1hcl, 1gih, 2whb, 2w06, 2vtn, 1jst, 1oiu, 1pxm, 1b38, 1fq1, 1vyw, 1h1p, 2wma, 2c69, 1urc, 1pxi, 2c6i, 1ykr, 2w17, 2c6k, 2c5y, 2uzd, 1wcc, 2j9m, 1vyz, 2vti, 1jvp, 1w98, 2wip, 1pkd, 1p5e, 2vts, 2c5p, 2uzn, 2b54, 1ke6, 1pxj, 2uzl, 2cci, 2g9x, 2bkz, 1y91, 2iw6, 1gij, 1r78, 1h0v, 2iw9, 1w8c, 1buh, 2bpm, 2bts, 1fvv, 1okw, 2a4l, 2vtp, 2c6t, 1fvt, 1qmz, 2w1h, 2vu3, 2b55, 1ogu, 1pf8, 1h1s, 2c5v, 2jgz, 2bhe, 1urw, 1oiy, 2c6l, 1f5q, 2c6o, 2vtl, 1ol1, 1h01, 2uzb, 2wfy, 1oir, 1oi9, 2vtj, 2cjm, 2c5n, 2wev, 2c5x, 2c6m, 1oit, 1gy3, 2v22, 2vv9, 1di8, 1gii, 2wmb, 1e9h, 1dm2, 2vto, 1h24, 2uzo, 2exm, 1h00, 2clx, 1pxp, 2cch, 2btr, 1b39, 1aq1, 1h0w, 1g5s, 1ckp, 1pxl, 1h28, 1ke8, 2vtr, 1h26, 1h07, 1e1x, 1y8y Activity: Transferase, with EC number 2.7.11.8, 2.7.11.9, 2.7.11.10, 2.7.11.11, 2.7.11.12, 2.7.11.13, 2.7.11.21, 2.7.11.22, 2.7.11.24, 2.7.11.25, 2.7.11.30 and 2.7.12.1 2.7.11.1, 2.7.11.8, 2.7.11.9, 2.7.11.10, 2.7.11.11, 2.7.11.12, 2.7.11.13, 2.7.11.21, 2.7.11.22, 2.7.11.24, 2.7.11.25, 2.7.11.30 and 2.7.12.1 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT 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 We have recently reported CDK inhibitors based on the 6-substituted pyrrolo[3,4-c]pyrazole core structure. Improvement of inhibitory potency against multiple CDKs, antiproliferative activity against cancer cell lines and optimization of the physico-chemical properties led to the identification of highly potent compounds. Compound 31 (PHA-793887) showed good efficacy in the human ovarian A2780, colon HCT-116 and pancreatic BX-PC3 carcinoma xenograft models and was well tolerated upon daily treatments by iv administration. It was identified as a drug candidate for clinical evaluation in patients with solid tumors. Optimization of 6,6-dimethyl pyrrolo[3,4-c]pyrazoles: Identification of PHA-793887, a potent CDK inhibitor suitable for intravenous dosing.,Brasca MG, Albanese C, Alzani R, Amici R, Avanzi N, Ballinari D, Bischoff J, Borghi D, Casale E, Croci V, Fiorentini F, Isacchi A, Mercurio C, Nesi M, Orsini P, Pastori W, Pesenti E, Pevarello P, Roussel P, Varasi M, Volpi D, Vulpetti A, Ciomei M Bioorg Med Chem. 2010 Mar 1;18(5):1844-53. Epub 2010 Jan 25. PMID:20153204 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Cyclin Cyclin-dependent kinase

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