1. Metabolic Enzyme/Protease
    Autophagy
  2. Farnesyl Transferase
    Autophagy

Lonafarnib (Synonyms: Sch66336)

Cat. No.: HY-15136 Purity: 99.42%
Handling Instructions

Lonafarnib is an orally bioavailable farnesyl protein transferase (FPTase) inhibitor for H-ras, K-ras and N-ras with IC50 of 1.9 nM, 5.2 nM and 2.8 nM, respectively.

For research use only. We do not sell to patients.

Lonafarnib Chemical Structure

Lonafarnib Chemical Structure

CAS No. : 193275-84-2

Size Price Stock Quantity
10 mM * 1 mL in DMSO USD 205 In-stock
Estimated Time of Arrival: December 31
5 mg USD 146 In-stock
Estimated Time of Arrival: December 31
10 mg USD 264 In-stock
Estimated Time of Arrival: December 31
50 mg   Get quote  
100 mg   Get quote  

* Please select Quantity before adding items.

Customer Review

  • Biological Activity

  • Protocol

  • Technical Information

  • Purity & Documentation

  • References

Description

Lonafarnib is an orally bioavailable farnesyl protein transferase (FPTase) inhibitor for H-ras, K-ras and N-ras with IC50 of 1.9 nM, 5.2 nM and 2.8 nM, respectively.

IC50 & Target

IC50: 1.9 nM (H-ras), 5.2 nM (K-ras), 2.8 nM (N-ras)[1]

In Vitro

Lonafarnib (Sch66336) potently inhibits Ha-Ras processing in whole cells and blocks the trans formed growth properties of fibroblasts and human tumor cell lines expressing activated Ki-Ras proteins[1]. All treatment groups containing Lonafarnib (10 µM) show a significantly higher level of unfarnesylated H-Ras (116-137%) compared to control treatment[2].

In Vivo

In mouse, rat, and monkey systems, Lonafarnib (Sch66336) has excellent oral bioavailability and pharmacokinetic properties. In the nude mouse, Lonafarnib demonstrates potent oral activity in a wide array of human tumor xenograft models including tumors of colon, lung, pancreas, prostate, and urinary bladder origin[1]. Lonafarnib alone (80 mg/kg by oral gavage, once daily) has limited ability to inhibit orthotopic U87 tumors compared to vehicle treated control animals (T/C of 0.67). The combination of XRT/Tem (2.5Gy/day for 2 days; 5 mg/kg by oral gavage 90 min prior to XRT) is designed to produce modest tumor growth inhibition in vivo(T/C of 0.42). Concurrent Lonafarnib/XRT/Tem (Lonafarnib 80 mg/kg by oral gavage, once daily, XRT 2.5Gy/day for 2 days, and Tem 5 mg/kg by oral gavage 90 min prior to XRT) provides the strongest growth reduction (T/C of 0.02) and is significantly more effective than XRT/Tem (p<0.04), with the majority of animals demonstrating a decrease in tumor volume (p<0.05) after two weeks and persisting after 4 weeks (p<0.05)[2].

Clinical Trial
Solvent & Solubility
In Vitro: 

10 mM in DMSO

Preparing
Stock Solutions
Concentration Solvent Mass 1 mg 5 mg 10 mg
1 mM 1.5654 mL 7.8269 mL 15.6539 mL
5 mM 0.3131 mL 1.5654 mL 3.1308 mL
10 mM 0.1565 mL 0.7827 mL 1.5654 mL
*Please refer to the solubility information to select the appropriate solvent.
References
Kinase Assay
[1]

FPTactivity is determined by measuring the transfer of [3H]farnesyl from [3H]farnesyl PPi to trichloroacetic acid-precipitable Ha-Ras-CVLS. GGPT-1 activity is similarly determined using [3H]geranylgeranyl diphosphate and Ha-Ras-CVLL as substrates[1].

MCE has not independently confirmed the accuracy of these methods. They are for reference only.

Cell Assay
[2]

CellTiter96 Aqueous Assay kit is used. Assays are performed with 5000 cells/well in a 96-well tissue culture plate. Plates are irradiated 24 h after drug exposure and assayed 96 h after XRT, with fresh drug treatments applied each day. For quantification, dye is added directly to each well, plates are washed as per the manufactures recommendation and cell viability determined by optical density. Significance is analyzed using the Student’s T-test. 12-well plates are seeded with 100,000 cells/well. Drug treatments are initiated 24 h after plating, and media is replaced every 24 h for a total of 96 h of drug exposure. Plates are irradiated after 24 h of drug exposure. Cells from triplicate sets of treatments are trypsonized and counted 48 h after irradation using a Z1 series coulter counter, and compared to cell numbers from wells counted on Day 1 (the day drug treatment is initiated). Proliferation after drug treatments are normalized to the control wells and expressed as % of the control treatment. Significance is analyzed using the Student’s T-test[2].

MCE has not independently confirmed the accuracy of these methods. They are for reference only.

Animal Administration
[2]

Mice[2]
Lonafarnib is given once daily at 80mg/kg with twice weekly weightings to ensure accurate dosing. Temozolomide (Tem) is given by gavage at 5 mg/kg 90 min prior to XRT. For irradiation, anesthetized mice are placed in a lead shielding apparatus which limited radiation exposure to the head only. Treatment (2.5Gy/day for two days) is delivered using a Gammacell 40 irradiator delivering 100 rads/min. For in vivo combination experiments, suboptimal doses of XRT/Tem are selected to permit identification of synergistic effects of Lonafarnib.

MCE has not independently confirmed the accuracy of these methods. They are for reference only.

References
Molecular Weight

638.82

Formula

C₂₇H₃₁Br₂ClN₄O₂

CAS No.

193275-84-2

SMILES

O=C(N1CCC(CC(N2CCC([[email protected]@H]3C4=C(Br)C=C(Cl)C=C4CCC5=CC(Br)=CN=C53)CC2)=O)CC1)N

Storage
Powder -20°C 3 years
  4°C 2 years
In solvent -80°C 6 months
  -20°C 1 month
Shipping

Room temperature in continental US; may vary elsewhere

  • Molarity Calculator

  • Dilution Calculator

The molarity calculator equation

Mass (g) = Concentration (mol/L) × Volume (L) × Molecular Weight (g/mol)

Mass   Concentration   Volume   Molecular Weight *
= × ×

The dilution calculator equation

Concentration (start) × Volume (start) = Concentration (final) × Volume (final)

This equation is commonly abbreviated as: C1V1 = C2V2

Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
× = ×
C1   V1   C2   V2

Inquiry Online

Your information is safe with us. * Required Fields.

Product name

 

Salutation

Applicant name *

 

Email address *

Phone number *

 

Organization name *

Country or Region *

 

Requested quantity *

Remarks

Bulk Inquiry

Inquiry Information

Product Name:
Lonafarnib
Cat. No.:
HY-15136
Quantity:

Lonafarnib

Cat. No.: HY-15136