Lonafarnib (SCH66336)

Catalog No.S2797 Batch:S279703

Technical Data

Formula

C₂₇H₃₁Br₂ClN₄O₂

Molecular Weight

638.82

CAS No.

193275-84-2

Solubility (25°C)*

In vitro

DMSO

100 mg/mL (156.53 mM)

Ethanol

2 mg/mL (3.13 mM)

Water

Insoluble

In vivo (Add solvents to the product individually and in order)

Clear solution

5%DMSO 1 40%PEG300 2 5%Tween80 3 50%ddH2O

5.0mg/ml

Taking the 1 mL working solution as an example, add 50 μL of 100 mg/ml clarified DMSO stock solution to 400 μL of PEG300, mix evenly to clarify it; add 50 μL of Tween80 to the above system, mix evenly to make it clear; then continue to add 500 μL of ddH2O to adjust the volume to 1 mL. The mixed solution should be used immediately for optimal results.

* <1 mg/ml means slightly soluble or insoluble.
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.
* Room temperature shipping (Stability testing shows this product can be shipped without any cooling measures.)

Preparing Stock Solutions

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

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]

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]

Protocol (from reference)

Cell Assay:^{^[2]}	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.
Animal Study:^{^[3]}	Animal Models NOD/SCID mice between 6–12 weeks of age Dosages 50 mg/kg Administration p.o. bid by oral gavage

Cell Assay:^{^[2]}

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.

Animal Study:^{^[3]}

Animal Models
NOD/SCID mice between 6–12 weeks of age
Dosages
50 mg/kg
Administration
p.o. bid by oral gavage

References

[4] Sun SY, et al. J Biol Chem, 2007, 282(26), 18800-18809.

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Customer Product Validation

: Data from [Data independently produced by , , Antiviral Res, 2017, 141:116-123]

: Data from [Data independently produced by , , J Cell Physiol, 2017, 232(1):192-201]

Selleck's Lonafarnib (SCH66336) has been cited by 20 publications

A farnesyl-dependent structural role for CENP-E in expansion of the fibrous corona [ J Cell Biol, 2024, 223(1)e202303007]	PubMed: 37934467
Microtubule nucleation from the fibrous corona by LIC1-pericentrin promotes chromosome congression [ Curr Biol, 2023, S0960-9822(23)00010-6]	PubMed: 36720222
Impact of a conserved N-terminal proline-rich region of the α-subunit of CAAX-prenyltransferases on their enzyme properties [ Cell Commun Signal, 2022, 20(1):118]	PubMed: 35941619
A farnesyltransferase inhibitor restores cognitive deficits in Tsc2+/- mice through inhibition of Rheb1 [ J Neurosci, 2022, JN-RM-0449-21]	PubMed: 35121635
Bacteria Are New Targets for Inhibitors of Human Farnesyltransferase [ Front Microbiol, 2021, 12:628283]	PubMed: 34917041
Growth Factor Receptor Signaling Inhibition Prevents SARS-CoV-2 Replication [ Mol Cell, 2020, 80(1):164-174.e4]	PubMed: 32877642
PML2-mediated Thread-Like Nuclear Bodies Mark Late Senescence in Hutchinson-Gilford Progeria Syndrome [ Aging Cell, 2020, 29]	PubMed: 32351002
Automated in vivo screen in zebrafish identifies Clotrimazole as targeting a metabolic vulnerability in a melanoma model. [ Dev Biol, 2020, 457(2):215-225]	PubMed: 30998907
The combination of lonafarnib and sorafenib induces cyclin D1 degradation via ATG3-mediated autophagic flux in hepatocellular carcinoma cells [ Aging (Albany NY), 2019, 11(15):5769-5785]	PubMed: 31409760
Loss of CENPF leads to developmental failure in mouse embryos [ Cell Cycle, 2019, 18(20):2784-2799]	PubMed: 31478449

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SHIPPING AND STORAGE
Selleck products are transported at room temperature. If you receive the product at room temperature, please rest assured, the Selleck Quality Inspection Department has conducted experiments to verify that the normal temperature placement of one month will not affect the biological activity of powder products. After collecting, please store the product according to the requirements described in the datasheet. Most Selleck products are stable under the recommended conditions.

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