3IBE

Crystal Structure of a Pyrazolopyrimidine Inhibitor Bound to PI3 Kinase Gamma

Summary for 3IBE

• Entry DOI: 10.2210/pdb3ibe/pdb
• Descriptor: Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit gamma isoform, SULFATE ION, 1-(4-{4-morpholin-4-yl-1-[1-(pyridin-3-ylcarbonyl)piperidin-4-yl]-1H-pyrazolo[3,4-d]pyrimidin-6-yl}phenyl)-3-pyridin-4-ylurea, ... (4 entities in total)
• Functional Keywords: pi3kinase inhibitor, atp-binding, kinase, nucleotide-binding, transferase
• Biological source: Homo sapiens (human)
• Cellular location: Cytoplasm : P48736
• Total number of polymer chains: 1
• Total formula weight: 111456.89

Authors

Bard, J.,Svenson, K. (deposition date: 2009-07-15, release date: 2009-09-01, Last modification date: 2023-09-06)

Primary citation

Zask, A.,Verheijen, J.C.,Curran, K.,Kaplan, J.,Richard, D.J.,Nowak, P.,Malwitz, D.J.,Brooijmans, N.,Bard, J.,Svenson, K.,Lucas, J.,Toral-Barza, L.,Zhang, W.G.,Hollander, I.,Gibbons, J.J.,Abraham, R.T.,Ayral-Kaloustian, S.,Mansour, T.S.,Yu, K.
ATP-Competitive Inhibitors of the Mammalian Target of Rapamycin: Design and Synthesis of Highly Potent and Selective Pyrazolopyrimidines.
J.Med.Chem., 52:5013-5016, 2009

PubMed Abstract: The mammalian target of rapamycin (mTOR), a central regulator of growth, survival, and metabolism, is a validated target for cancer therapy. Rapamycin and its analogues, allosteric inhibitors of mTOR, only partially inhibit one mTOR protein complex. ATP-competitive, global inhibitors of mTOR that have the potential for enhanced anticancer efficacy are described. Structural features leading to potency and selectivity were identified and refined leading to compounds with in vivo efficacy in tumor xenograft models.

PubMed: 19645448
DOI: 10.1021/jm900851f

Experimental method

X-RAY DIFFRACTION (2.798 Å)