lonafarnib   Click here for help

GtoPdb Ligand ID: 8024

Synonyms: SCH 66336 | SCH-66336 | SCH66336 | Zokinvy®
Approved drug PDB Ligand
lonafarnib is an approved drug (FDA (2020), ENA (2022))
Compound class: Synthetic organic
Comment: Lonafarnib is an orally bioavailable molecule which inhibits farnesyl protein transferase, an enzyme that is responsible for catalysing the transfer of a 15-carbon isoprenoid group to a variety of cellular proteins including RAS [7].
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2D Structure
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Physico-chemical Properties
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Hydrogen bond acceptors 6
Hydrogen bond donors 1
Rotatable bonds 5
Topological polar surface area 79.53
Molecular weight 636.05
XLogP 4.45
No. Lipinski's rules broken 0
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Canonical SMILES Clc1cc(Br)c2c(c1)CCc1c(C2C2CCN(CC2)C(=O)CC2CCN(CC2)C(=O)N)ncc(c1)Br
Isomeric SMILES Clc1cc(Br)c2c(c1)CCc1c([C@@H]2C2CCN(CC2)C(=O)CC2CCN(CC2)C(=O)N)ncc(c1)Br
InChI InChI=1S/C27H31Br2ClN4O2/c28-20-12-19-2-1-18-13-21(30)14-22(29)24(18)25(26(19)32-15-20)17-5-9-33(10-6-17)23(35)11-16-3-7-34(8-4-16)27(31)36/h12-17,25H,1-11H2,(H2,31,36)/t25-/m1/s1
Bioactivity Comments
Data in the table shows the ability of lonafarnib to inhibit farnesyltransferase-mediated farnesylation of human RAS proteins.
Selectivity at enzymes
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Target Sp. Type Action Value Parameter Concentration range (M) Reference
HRAS Hs Inhibitor Inhibition 8.7 pIC50 - 5
pIC50 8.7 (IC50 1.9x10-9 M) [5]
Description: Measuring inhibition of farnesylation of HRAS by human farnesyltransferase
NRAS Hs Inhibitor Inhibition 8.6 pIC50 - 5
pIC50 8.6 (IC50 2.8x10-9 M) [5]
Description: Measuring inhibition of farnesylation of NRAS by human farnesyltransferase
KRAS Hs Inhibitor Inhibition 8.3 pIC50 - 5
pIC50 8.3 (IC50 5.2x10-9 M) [5]
Description: Measuring inhibition of farnesylation of KRAS4B by human farnesyltransferase