product name Lonafarnib
Description: Lonafarnib (also known as SCH66336) is an orally bioavailable and potent FPTase inhibitor for H-ras, K-ras-4B and N-ras with IC50 of 1.9 nM, 5.2 nM and 2.8 nM in cell-free assays, respectively. Lonafarnib is also a synthetic tricyclic derivative of carboxamide with antineoplastic properties. Lonarfanib binds to and inhibits farnesyl transferase, an enzyme involved in the post-translational modification and activation of Ras proteins.
References: Cancer Res. 1998;58(21):4947-56; Cancer Res. 2003;63(16):4796-800; Cancer Res. 2001;61(11):4425-31.
638.82
Formula
C27H31Br2ClN4O2
CAS No.
193275-84-2
Storage
-20℃ for 3 years in powder form
-80℃ for 2 years in solvent
Solubility (In vitro)
DMSO: 127 mg/mL (198.8 mM)
Water: <1 mg/mL
Ethanol: 127 mg/mL (198.8 mM)
Solubility (In vivo)
Synonyms
SCH66336
other peoduct :
| In Vitro |
In vitro activity: SCH66336 at concentration ranging from 0.1 μM to 8 μM suppress growth and induce apoptosis of human head and neck squamous carcinoma cells (HNSCC) in a dose and time dependent manner. SCH66336 (8 μM) suppresses protein kinase B/Akt activity as well as the phosphorylation of the Akt substrates glycogen synthase kinase (GSK)-3β, forkhead transcription factor, and BAD in SqCC/Y1 cells. SCH66336 demonstrate variable antiproliferative effects against the cell lines, with IC50 ranging from 0.6 μM to 32.3 μM. Lonafarnib induces a CCAAT/enhancer-binding protein homologous protein (CHOP)-dependent transactivation of the DR5 promoter, thus induces CHOP-dependent DR5 up-regulation. Lonafarnib (< 10 μM) activates caspase-8 and its downstream caspases, thus induces caspase-8-dependent apoptosis in H1792 cells. Lonafarnib (5 μM) up-regulate DR5 expression, increase cell-surface DR5 distribution, and enhance tumor necrosis factor-related apoptosis-inducing ligand-induced apoptosis in H1792 cells. Kinase Assay: Cell Assay: The cells are seeded in 96-well cell-culture cluster plates at a density that allowed control cultures to grow exponentially for 5 days. After 24 hours, the cells are treated with different concentrations of SCH66336. SCH66336 is dissolved in DMSO. Control cultures received the same amount of DMSO as the treated cultures do. Cell numbers are estimated after 5 days of treatment by SRB assay. The percentage of growth inhibition is calculated by using the equation: percentage growth inhibition = (1 − At/Ac) × 100, where At and Ac represent the absorbance in treated and control cultures, respectively. The drug concentration causing a 50% cell growth inhibition (IC50), is determined by interpolation from dose-response curves. |
|---|---|
| In Vivo | SCH66336 inhibits HTBI77 human lung carcinoma xenograft growth in nude mice in a dose-dependent fashion. SCH66336 dosed at 50 mg/kg p.o. bid by oral gavage inhibits tumor growth with up to 69% growth inhibition after 21 days of treatment in NOD/SCID mice bearing s.c. flank XEN01, XEN05 or XEN08 GBM xenografts. |
| Animal model | NOD/SCID mice between 6–12 weeks of age |
| Formulation & Dosage | Dissolved in 20% (w/v) HPβCD; 50 mg/kg; Oral gavage |
| References | Cancer Res. 1998 Nov 1;58(21):4947-56; Cancer Res. 2003 Aug 15;63(16):4796-800; Cancer Res. 2001 Jun 1;61(11):4425-31. |
