lonafarnib

Lonafarnib (Sch66336) is an orally bioavailable FPTase inhibitor for H-ras, K-ras-4B, and N-ras (IC50: 1.9/5.2/2.8 nM).

(Rac)-Lonafarnib (Sch66336 racemate) is the racemic form of the potent, orally active farnesyl transferase (FTase) inhibitor, Lonafarnib. It effectively inhibits H-ras, K-ras, and N-ras with IC50 values of 1.9 nM, 5.2 nM, and 2.8 nM, respectively, and exhibits activities against the hepatitis delta virus (HDV).

AZD-3409 is a potent prenyl transferase inhibitor. AZD-3409 showed higher potency than lonafarnib. The mean IC(50) for cytotoxicity of AZD3409 was 510 in MEF cells, 10,600 in A549 cells and 6,170 in MCF7 cells, respectively. In these cells, the IC(50) for FTase activity of AZD3409 ranged from 3.0 to 14.2 nM and of lonafarnib from 0.26 to 31.3 nM. AZD3409 inhibits farnesylation to a higher extent than geranylgeranylation. Both inhibition of farnesylation and geranylgeranylation could not be correlated to the antiproliferative activity of the drug. AZD3409 might be active in gefitinib-resistant breast carcinoma.