4ANM

Complex of CK2 with a CDC7 inhibitor

Summary for 4ANM

• Entry DOI: 10.2210/pdb4anm/pdb
• Related: 1DAW 1DAY 1DS5 1F0Q 1J91 1JAM 1LP4 1LPU 1LR4 1M2P 1M2Q 1M2R 1OM1 1ZOE 1ZOG 1ZOH
• Descriptor: CASEIN KINASE II SUBUNIT ALPHA, 8-BROMANYL-2-[[(3S)-3-OXIDANYLPYRROLIDIN-1-YL]METHYL]-3H-[1]BENZOFURO[3,2-D]PYRIMIDIN-4-ONE (3 entities in total)
• Functional Keywords: transferase
• Biological source: ZEA MAYS (MAIZE)
• Total number of polymer chains: 1
• Total formula weight: 39944.58

Authors

Stout, T.J. (deposition date: 2012-03-20, release date: 2012-05-23, Last modification date: 2024-05-01)

Primary citation

Koltun, E.S.,Tsuhako, A.L.,Brown, D.S.,Aay, N.,Arcalas, A.,Chan, V.,Du, H.,Engst, S.,Ferguson, K.,Franzini, M.,Galan, A.,Holst, C.R.,Huang, P.,Kane, B.,Kim, M.H.,Li, J.,Markby, D.,Mohan, M.,Noson, K.,Plonowski, A.,Richards, S.J.,Robertson, S.,Shaw, K.,Stott, G.,Stout, T.J.,Young, J.,Yu, P.,Zaharia, C.A.,Zhang, W.,Zhou, P.,Nuss, J.M.,Xu, W.,Kearney, P.C.
Discovery of Xl413, a Potent and Selective Cdc7 Inhibitor.
Bioorg.Med.Chem.Lett., 22:3727-, 2012

PubMed Abstract: CDC7 is a serine/threonine kinase that has been shown to be required for the initiation and maintenance of DNA replication. Up-regulation of CDC7 is detected in multiple tumor cell lines, with inhibition of CDC7 resulting in cell cycle arrest. In this paper, we disclose the discovery of a potent and selective CDC7 inhibitor, XL413 (14), which was advanced into Phase 1 clinical trials. Starting from advanced lead 3, described in a preceding communication, we optimized the CDC7 potency and selectivity to demonstrate in vitro CDC7 dependent cell cycle arrest and in vivo tumor growth inhibition in a Colo-205 xenograft model.

PubMed: 22560567
DOI: 10.1016/J.BMCL.2012.04.024

Experimental method

X-RAY DIFFRACTION (1.7 Å)