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].
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2D Structure
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Physico-chemical Properties
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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
SMILES / InChI / InChIKey
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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)
InChI Key BYWWNRBKPCPJMG-UHFFFAOYSA-N
References
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]