PHT-427   Click here for help

GtoPdb Ligand ID: 8009

Synonyms: PHT 427 | PHT427
Compound class: Synthetic organic
Comment: PHT-427 is a novel dual inhibitor of 3-phosphoinositide dependent protein kinase 1 (PDK1) and Akt (protein kinase B) [3]. The original identification of PHT-427 (compound 14) as an Akt inhibitor is described in [1] where it is shown to bind to the pleckstrin homology (PH) domain of Akt, not to the catalytic ATP binding site. PDK1 activates Akt by phosphorylating Thr308 in Akt's kinase domain.
The PDK1/Akt signaling pathway plays a key role in cancer cell growth, survival, and tumour angiogenesis and represents a promising target for oncology therapeutics [2,4].
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 5
Hydrogen bond donors 1
Rotatable bonds 14
Topological polar surface area 108.57
Molecular weight 409.19
XLogP 8.96
No. Lipinski's rules broken 2
Click here for help
Canonical SMILES CCCCCCCCCCCCc1ccc(cc1)S(=O)(=O)Nc1nncs1
Isomeric SMILES CCCCCCCCCCCCc1ccc(cc1)S(=O)(=O)Nc1nncs1
InChI InChI=1S/C20H31N3O2S2/c1-2-3-4-5-6-7-8-9-10-11-12-18-13-15-19(16-14-18)27(24,25)23-20-22-21-17-26-20/h13-17H,2-12H2,1H3,(H,22,23)
1. Du-Cuny L, Song Z, Moses S, Powis G, Mash EA, Meuillet EJ, Zhang S. (2009)
Computational modeling of novel inhibitors targeting the Akt pleckstrin homology domain.
Bioorg Med Chem, 17 (19): 6983-92. [PMID:19734051]
2. Hanada M, Feng J, Hemmings BA. (2004)
Structure, regulation and function of PKB/AKT--a major therapeutic target.
Biochim Biophys Acta, 1697 (1-2): 3-16. [PMID:15023346]
3. Meuillet EJ, Zuohe S, Lemos R, Ihle N, Kingston J, Watkins R, Moses SA, Zhang S, Du-Cuny L, Herbst R et al.. (2010)
Molecular pharmacology and antitumor activity of PHT-427, a novel Akt/phosphatidylinositide-dependent protein kinase 1 pleckstrin homology domain inhibitor.
Mol Cancer Ther, 9 (3): 706-17. [PMID:20197390]
4. Shiojima I, Walsh K. (2002)
Role of Akt signaling in vascular homeostasis and angiogenesis.
Circ Res, 90 (12): 1243-50. [PMID:12089061]