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Literature summary for 2.7.1.153 extracted from

  • Rewcastle, G.W.; Gamage, S.A.; Flanagan, J.U.; Frederick, R.; Denny, W.A.; Baguley, B.C.; Kestell, P.; Singh, R.; Kendall, J.D.; Marshall, E.S.; Lill, C.L.; Lee, W.J.; Kolekar, S.; Buchanan, C.M.; Jamieson, S.M.; Shepherd, P.R.
    Synthesis and biological evaluation of novel analogues of the pan class I phosphatidylinositol 3-kinase (PI3K) inhibitor 2-(difluoromethyl)-1-[4,6-di(4-morpholinyl)-1,3,5-triazin-2-yl]-1H-benzimidazole (ZSTK474) (2011), J. Med. Chem., 54, 7105-7126.
    View publication on PubMed
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Crystallization (Commentary)

Crystallization (Comment) Organism
structure activity relationship study of inhibitor 2-(difluoromethyl)-1-[4,6-di-(4-morpholinyl)-1,3,5-triazin-2-yl]-1H-benzimidazole, i.e. ZSTK474, with catalytic subunit gamma isoform, PDB entry 2CHX Homo sapiens

Inhibitors

Inhibitors Comment Organism Structure
2-(difluoromethyl)-1-[4,6-di-(4-morpholinyl)-1,3,5-triazin-2-yl]-1H-benzimidazole lead compound for structure-activity study Homo sapiens
6-amino-2-(difluoromethyl)-1-[4,6-di(4-morpholinyl)-1,3,5-triazin-2-yl]-4-methoxy-1H-benzimidazole inhibitory against all three class Ia PI 3-kinase enzymes, i.e. p110alpha, p110beta, and p110delta, and also displays significant potency against two mutant forms of the p110alpha isoform, H1047R and E545K. In an in vivo U87MG human glioblastoma tumor xenograftmodel in Rag1-/- mice, and at a dose of 50mg/kg given by intraperitoneal injection it dramatically reduces cancer growth by 81% compared to untreated controls Homo sapiens

Organism

Organism UniProt Comment Textmining
Homo sapiens P48736 catalytic subunit gamma isoform
-

IC50 Value

IC50 Value IC50 Value Maximum Comment Organism Inhibitor Structure
0.00000022
-
 isoform p110alpha, pH not specified in the publication, temperature not specified in the publication Homo sapiens 6-amino-2-(difluoromethyl)-1-[4,6-di(4-morpholinyl)-1,3,5-triazin-2-yl]-4-methoxy-1H-benzimidazole
0.00000038
-
 isoform p110delta, pH not specified in the publication, temperature not specified in the publication Homo sapiens 6-amino-2-(difluoromethyl)-1-[4,6-di(4-morpholinyl)-1,3,5-triazin-2-yl]-4-methoxy-1H-benzimidazole
0.0000014
-
 isoform p110beta, pH not specified in the publication, temperature not specified in the publication Homo sapiens 6-amino-2-(difluoromethyl)-1-[4,6-di(4-morpholinyl)-1,3,5-triazin-2-yl]-4-methoxy-1H-benzimidazole