1Z5M: Crystal Structure Of N1-[3-[[5-bromo-2-[[3-[(1-pyrrolidinylcarbonyl) Amino]phenyl]amino]-4-pyrimidinyl]amino]propyl]-2,2- Dimethylpropanediamide Complexed With Human Pdk1

The phosphoinositide 3-kinase/3-phosphoinositide-dependent kinase 1 (PDK1)/Akt signaling pathway plays a key role in cancer cell growth, survival, and tumor angiogenesis and represents a promising target for anticancer drugs. Here, we describe three potent PDK1 inhibitors, BX-795, BX-912, and BX-320 (IC(50) = 11-30 nm) and their initial biological characterization. The inhibitors blocked PDK1/Akt signaling in tumor cells and inhibited the anchorage-dependent growth of a variety of tumor cell lines in culture or induced apoptosis. A number of cancer cell lines with elevated Akt activity were >30-fold more sensitive to growth inhibition by PDK1 inhibitors in soft agar than on tissue culture plastic, consistent with the cell survival function of the PDK1/Akt signaling pathway, which is particularly important for unattached cells. BX-320 inhibited the growth of LOX melanoma tumors in the lungs of nude mice after injection of tumor cells into the tail vein. The effect of BX-320 on cancer cell growth in vitro and in vivo indicates that PDK1 inhibitors may have clinical utility as anticancer agents.
PDB ID: 1Z5MDownload
MMDB ID: 33009
PDB Deposition Date: 2005/3/18
Updated in MMDB: 2017/11
Experimental Method:
x-ray diffraction
Resolution: 2.17  Å
Source Organism:
Similar Structures:
Biological Unit for 1Z5M: monomeric; determined by author
Molecular Components in 1Z5M
Label Count Molecule
Protein (1 molecule)
3-phosphoinositide Dependent Protein Kinase-1(Gene symbol: PDPK1)
Molecule annotation
Chemicals (6 molecules)
* Click molecule labels to explore molecular sequence information.

Citing MMDB