Reference
Wang, S., Zaharevitz, DW, Sharma, R, Marquez, VE, Lewin, NE, DU, L, Blumberg, PM, and Milne, GWA. The Discovery of Novel, Structurally Diverse PK-C Agonists through Computer 3D-Database Pharmacophore Search. Molecular Modeling Studies. J. Med. Chem. 37:4479-4489 (1994).We have used a pharmacophore derived from phorbol to find compounds that bind to protein kinase C (PKC)
Note: The 2D pictures here are hot links to the 3D pdb file. For the necessary information on setting up your client to handle these files see http://www.ch.ic.ac.uk/chemical_mime_config.html )
phorbol, 12,13 dibenzoate
The oxygens at C3, C9, and C20 form a three point pharmacophore (Rando and Kishi, Biochem. 31:2211-2218, 1992 and Nakamura, et. al., Proc. Natl. Acad> Sci. USA 86:9672-9676, 1989 )that we used to construct the following query:
The Chem-X query is available.
The following active compounds were found:
NSC 54564 KI = 16 micromolar
NSC 115290 KI = 8 micromolar
NSC 135516 KI = 27 micromolar
NSC 232034 KI = 13 micromolar
NSC 237672 KI = 40 micromolar