PDK1/Akt/Flt dual pathway inhibitor   Click here for help

GtoPdb Ligand ID: 6022

Synonyms: AG-L-66494 | GNF-Pf-3800
Compound class: Synthetic organic
Comment: This compound is a mixture of tautomers (KP372-1A and KP372-1B), present in almost equal amounts. Our image shows the structure of KP372-1B.
This compound has been shown to directly inhibit both PDK1 and Akt activities in in vitro kinase assays in a dose-dependent manner and block cellular phosphorylation of Akt at both Ser473 and Thr308 residues [6].
Click here for help
2D Structure
Click here for help
Click here for structure editor
Physico-chemical Properties
Click here for help
Hydrogen bond acceptors 6
Hydrogen bond donors 0
Rotatable bonds 0
Topological polar surface area 85.93
Molecular weight 224.04
XLogP 1.33
No. Lipinski's rules broken 0
Click here for help
Canonical SMILES O=C1c2nn3nnnc3nc2c2c1cccc2
Isomeric SMILES O=C1c2nn3nnnc3nc2c2c1cccc2
InChI InChI=1S/C10H4N6O/c17-9-6-4-2-1-3-5(6)7-8(9)13-16-10(11-7)12-14-15-16/h1-4H
1. Anastassiadis T, Deacon SW, Devarajan K, Ma H, Peterson JR. (2011)
Comprehensive assay of kinase catalytic activity reveals features of kinase inhibitor selectivity.
Nat Biotechnol, 29 (11): 1039-45. [PMID:22037377]
2. Gao Y, Davies SP, Augustin M, Woodward A, Patel UA, Kovelman R, Harvey KJ. (2013)
A broad activity screen in support of a chemogenomic map for kinase signalling research and drug discovery.
Biochem J, 451 (2): 313-28. [PMID:23398362]
3. Koul D, Shen R, Bergh S, Sheng X, Shishodia S, Lafortune TA, Lu Y, de Groot JF, Mills GB, Yung WK. (2006)
Inhibition of Akt survival pathway by a small-molecule inhibitor in human glioblastoma.
Mol Cancer Ther, 5 (3): 637-44. [PMID:16546978]
4. Mandal M, Kim S, Younes MN, Jasser SA, El-Naggar AK, Mills GB, Myers JN. (2005)
The Akt inhibitor KP372-1 suppresses Akt activity and cell proliferation and induces apoptosis in thyroid cancer cells.
Br J Cancer, 92 (10): 1899-905. [PMID:15870708]
5. Mandal M, Younes M, Swan EA, Jasser SA, Doan D, Yigitbasi O, McMurphey A, Ludwick J, El-Naggar AK, Bucana C et al.. (2006)
The Akt inhibitor KP372-1 inhibits proliferation and induces apoptosis and anoikis in squamous cell carcinoma of the head and neck.
Oral Oncol, 42 (4): 430-9. [PMID:16442835]
6. Zeng Z, Samudio IJ, Zhang W, Estrov Z, Pelicano H, Harris D, Frolova O, Hail Jr N, Chen W, Kornblau SM et al.. (2006)
Simultaneous inhibition of PDK1/AKT and Fms-like tyrosine kinase 3 signaling by a small-molecule KP372-1 induces mitochondrial dysfunction and apoptosis in acute myelogenous leukemia.
Cancer Res, 66 (7): 3737-46. [PMID:16585200]