L-739,750   Click here for help

GtoPdb Ligand ID: 8030

Synonyms: L 739750
PDB Ligand
Compound class: Synthetic organic
Comment: The discovery of L-739,750 is described in [2]. L-739,750 is a peptidomimetic farnesyltransferase inhibitor (FTI). Experimentally the compound is administered as a methyl ester prodrug (L-739,749) [2].
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2D Structure
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Physico-chemical Properties
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Hydrogen bond acceptors 9
Hydrogen bond donors 4
Rotatable bonds 18
Topological polar surface area 195
Molecular weight 517.23
XLogP -0.11
No. Lipinski's rules broken 1
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Canonical SMILES CCC(C(NCC(CS)N)COC(C(=O)NC(C(=O)O)CCS(=O)(=O)C)Cc1ccccc1)C
Isomeric SMILES CC[C@@H]([C@H](NC[C@H](CS)N)CO[C@H](C(=O)N[C@H](C(=O)O)CCS(=O)(=O)C)Cc1ccccc1)C
InChI InChI=1S/C23H39N3O6S2/c1-4-16(2)20(25-13-18(24)15-33)14-32-21(12-17-8-6-5-7-9-17)22(27)26-19(23(28)29)10-11-34(3,30)31/h5-9,16,18-21,25,33H,4,10-15,24H2,1-3H3,(H,26,27)(H,28,29)/t16-,18+,19-,20+,21-/m0/s1
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Mechanism Of Action and Pharmacodynamic Effects Click here for help
FTIs inhibit the C-terminal prenylation of many proteins involved in signal transduction, but are being investigated mainly as inhibitors of deregulated RAS activity in transformed cells. Blocking prenylation of RAS oncogenic proteins prevents their correct membrane tethering, and thereby effects reduced RAS signalling activity and increased cancer cell apoptosis. However, the promise of FTIs has not been bourne out in clinical trials [1], perhaps due to redundancy in the system which sees geranylgeranyltransferase taking over the prenylation process, when farnesyltransferase is inhibited.