Comparison

Lonafarnib (SCH66336) European Partner

Item no. S2797-1000
Manufacturer Selleckchem
CASRN 193275-84-2
Amount 1 g
Quantity options 10 mg 100 mg 1 g 10 g 10 mM/1 mL 200 mg 25 mg 5 mg 5 g
Category
Type Inhibitors
Specific against other
Smiles C1CN(CCC1CC(=O)N2CCC(CC2)C3C4=C(CCC5=C3N=CC(=C5)Br)C=C(C=C4Br)Cl)C(=O)N
ECLASS 10.1 32160490
ECLASS 11.0 32160490
UNSPSC 12000000
Alias H-ras,K-ras-4B,N-ras,Transferase
Similar products Lonafarnib
Available
Storage Conditions
2 years -80 in solvent
Molecular Weight
638, 82
Administration
p.o. bid by oral gavage
Animal Models
NOD/SCID mice between 6–12 weeks of age
Cell lines
UMSCC10B, UMSCC14B, UMSCC17B, UMSCC22B, and UMSCC35, UMSCC38 cell lines
Clinical Trials
SCH66336 has finished phase 2 clinical trial in patients with Metastatic Breast Cancer
Concentrations
0.1 uM - 8 uM
Dosages
50 mg/kg
Formulation
20% (w/v) HPbetaCD
IC50
1.9 nM, 1.9 nM, 1.9 nM, 1.9 nM, 1.9 nM, 1.9 nM
In vitro
SCH66336 at concentration ranging from 0.1 uM to 8 uM suppress growth and induce apoptosis of human head and neck squamous carcinoma cells (HNSCC) in a dose and time dependent manner. SCH66336 (8 uM) suppresses protein kinase B/Akt activity as well as the phosphorylation of the Akt substrates glycogen synthase kinase (GSK)-3beta, forkhead transcription factor, and BAD in SqCC/Y1 cells. [2] SCH66336 demonstrate variable antiproliferative effects against the cell lines, with IC50 ranging from 0.6 uM to 32.3 uM. [3] 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 uM) activates caspase-8 and its downstream caspases, thus induces caspase-8-dependent apoptosis in H1792 cells. Lonafarnib (5 uM) up-regulate DR5 expression, increase cell-surface DR5 distribution, and enhance tumor necrosis factor-related apoptosis-inducing ligand-induced apoptosis in H1792 cells.[4]
In vivo
SCH66336 inhibits HTBI77 human lung carcinoma xenograft growth in nude mice in a dose-dependent fashion. [1] 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. [3]
Incubation Time
24 hours
Method
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) x 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.
Solubility (25C)
DMSO 127 mg/mL, Water <1 mg/mL, Ethanol 127 mg/mL
Information
Lonafarnib (SCH66336) is an orally bioavailable 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. Phase 3.
Chemical Name
1-Piperidinecarboxamide, 4-[2-[4-[(11R)-3, 10-dibromo-8-chloro-6, 11-dihydro-5H-benzo[5, 6]cyclohepta[1, 2-b]pyridin-11-yl]-1-piperidinyl]-2-oxoethyl]-

Note: The presented information and documents (Manual, Product Datasheet, Safety Datasheet and Certificate of Analysis) correspond to our latest update and should serve for orientational purpose only. We do not guarantee the topicality. We would kindly ask you to make a request for specific requirements, if necessary.

All products are intended for research use only (RUO). Not for human, veterinary or therapeutic use.

Amount: 1 g
Available: In stock
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