Home Metabolism Transferase inhibitor - Ras inhibitor Lonafarnib (SCH66336) For research use only.

Lonafarnib (SCH66336)

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.

Lonafarnib (SCH66336) Chemical Structure

Lonafarnib (SCH66336) Chemical Structure

CAS No. 193275-84-2

Purity & Quality Control

Lonafarnib (SCH66336) Related Products

Signaling Pathway

Transferase Signaling Pathways

Transferase Signaling Pathway

Cell Data

Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
Cos-1 monkey kidney cells Function assay Inhibition of Protein farnesyltransferase in Cos-1 monkey kidney cells expressing H-Ras-val, IC50=0.0019 μM 12190309
COS-7 monkey cells Function assay Inhibiting the farnesylation of H-ras proteins in COS-7 monkey cells transiently expressing H-ras[Val12]-CVLS in the whole cell assay, IC50=0.01 μM 9822558
MCF-7 tumor cell line Growth inhibition assay Compound was measured for inhibition of MCF-7 tumor cell line in breast under soft agar assay, IC50=0.05 μM 9822558
HCT116 Growth inhibition assay Compound was measured for inhibition of HCT116 tumor cell line in colon under soft agar assay, IC50=0.07 μM 9822558
NIH-H tumor cell lines Growth inhibition assay Compound ability to inhibit anchorage-independent growth of NIH-H tumor cell lines in soft agar, IC50=0.072 μM 9822558
NIH3T3 cells Function assay Inhibition of Ras farnesylation in H-Ras transformed NIH3T3 cells, EC50=0.1 μM 15454228
NIH-K tumor cell lines Growth inhibition assay Compound ability to inhibit anchorage-independent growth of NIH-K tumor cell lines in soft agar, IC50=0.5 μM 9822558
Cos-1 Function assay Inhibition of Protein farnesyltransferase in Cos-1 monkey kidney cells expressing H-Ras-val, IC50 = 0.0019 μM. 12190309
Cos-1 Function assay Effect on Ras processing in Cos-1 monkey kidney cells expressing either H-Ras-Val 12-CVLS or H-Ras-Val12, IC50 = 0.01 μM. 10411485
COS7 Function assay Inhibition of FTase in human COS7 cells, IC50 = 0.01 μM. 20925433
H-Ras transformed cells Function assay Inhibition of soft agar colony formation in H-Ras transformed cells, IC50 = 0.07 μM. 15501065
NIH3T3 Function assay Effective concentration against Ha-RAS processing in NIH3T3 ras-transformed cells, EC50 = 0.16 μM. 12657284
NIH3T3 Function assay TP_TRANSPORTER: inhibition of DNR efflux (DNR: ? uM) in MDR1-expressing NIH3T3 cells, IC50 = 2.7 μM. 11606389
A673 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for A673 cells 29435139
DAOY qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for DAOY cells 29435139
Saos-2 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Saos-2 cells 29435139
BT-37 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for BT-37 cells 29435139
RD qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for RD cells 29435139
BT-12 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for BT-12 cells 29435139
MG 63 (6-TG R) qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for MG 63 (6-TG R) cells 29435139
NB1643 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for NB1643 cells 29435139
OHS-50 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for OHS-50 cells 29435139
Rh41 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Rh41 cells 29435139
SJ-GBM2 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for SJ-GBM2 cells 29435139
SK-N-MC qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for SK-N-MC cells 29435139
NB-EBc1 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for NB-EBc1 cells 29435139
LAN-5 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for LAN-5 cells 29435139
Caco-2 Cytotoxicity assay 48 hours Determination of IC50 values for inhibition of SARS-CoV-2 induced cytotoxicity of Caco-2 cells after 48 hours by high content imaging, IC50 = 5.68 μM. ChEMBL
Caco-2 Toxicity assay 48 hours Toxicity against Caco-2 cells determined at 48 hours by intracellular ATP concentration using the CellTiter-Glo Luminescent Cell Viability Assay, CC50 = 10.71 μM. ChEMBL
Click to View More Cell Line Experimental Data

Biological Activity

Description 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.
Targets
H-ras [1]
(Cell-free assay)		 N-ras [1]
(Cell-free assay)		 K-ras-4B [1]
(Cell-free assay)
1.9 nM 2.8 nM 5.2 nM
In vitro
In vitro 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. [2] SCH66336 demonstrate variable antiproliferative effects against the cell lines, with IC50 ranging from 0.6 μM to 32.3 μM. [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 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.[4]
Cell Research Cell lines UMSCC10B, UMSCC14B, UMSCC17B, UMSCC22B, and UMSCC35, UMSCC38 cell lines
Concentrations 0.1 μM - 8 μM
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) × 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.
Experimental Result Images Methods Biomarkers Images PMID
Western blot p-ERK / p-SAPK / p-JNK PARP / cleaved-PARP / pro-caspase3 / cleaved-caspase3 / Bcl-2 Cyclin D / CDK6 / CDK4 / SKP2 LC3A / LC3B 29285232
Growth inhibition assay Cell number Cell viability 29069775
In Vivo
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]
Animal Research Animal Models NOD/SCID mice between 6–12 weeks of age
Dosages 50 mg/kg
Administration p.o. bid by oral gavage
NCT Number Recruitment Conditions Sponsor/Collaborators Start Date Phases
NCT05953545 Not yet recruiting
Chronic Hepatitis Delta
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)|National Institutes of Health Clinical Center (CC)
 May 15 2024 Phase 2
NCT02579044 Enrolling by invitation
Progeria
Boston Children''s Hospital
 December 2015 Phase 1|Phase 2
NCT02430181 Completed
Chronic Hepatitis D Infection
Eiger BioPharmaceuticals
 November 2014 Phase 2
NCT01495585 Completed
Hepatitis D
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)|National Institutes of Health Clinical Center (CC)
 December 2011 Phase 2
NCT01232881 Terminated
Breast Cancer
Hoosier Cancer Research Network|United States Department of Defense|Indiana University School of Medicine|Emory University
 August 2009 --
NCT00916747 Active not recruiting
Progeria
Boston Children''s Hospital|Schering-Plough|Merck Sharp & Dohme LLC|Eiger BioPharmaceuticals
 August 2009 Phase 2

Chemical Information & Solubility

Molecular Weight 638.82 Formula

C27H31Br2ClN4O2
CAS No. 193275-84-2 SDF Download Lonafarnib (SCH66336) SDF
Smiles C1CN(CCC1CC(=O)N2CCC(CC2)C3C4=C(CCC5=C3N=CC(=C5)Br)C=C(C=C4Br)Cl)C(=O)N
Storage (From the date of receipt)

In vitro
Batch:

DMSO : 127 mg/mL ( (198.8 mM) Moisture-absorbing DMSO reduces solubility. Please use fresh DMSO.)

Ethanol : 127 mg/mL

Water : Insoluble


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In vivo
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Tech Support

Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

Handling Instructions

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