Cat. No.: HY-15136

Lonafarnib

(Synonyms: Sch66336)

14 Cited Publications

Customer Review

Based on 14 publication(s) in Google Scholar

Lonafarnib (Sch66336) is a potent and orally active, and CNS-penetrant farnesyl transferase (FTase) inhibitor. Lonafarnib inhibits the activities of H-ras, K-ras and N-ras with IC₅₀ values of 1.9 nM, 5.2 nM and 2.8 nM, respectively. Lonafarnib also has anti-hepatitis delta virus (HDV) activities.

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

Purity: 99.85%
CAS No.: 193275-84-2
Formula: C₂₇H₃₁Br₂ClN₄O₂
Molecular Weight:638.82

Storage:

Powder -20°C, 3 years , 4°C, 2 years ; In solvent -80°C, 2 years , -20°C, 1 year

Lonafarnib Chemical Structure

CAS No.: 193275-84-2

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Strong Fluorescence Signal / Multi-Disciplinary Applications / High Fluorescence Specificity

Biological Activity
- Description
- IC₅₀ & Target
- Cellular Effect
- In Vitro
- In Vivo
- Clinical Trial
Chemical Information
Publications (14)
Solvent & Solubility
- In Vitro
- In Vivo
Protocol
Purity & Documentation
References
Help & FAQs
Bioz

Biological Activity

Description

IC₅₀ & Target

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

All Ras Isoforms :

Cellular Effect

Cell Line	Type	Value	Description	References
Caco-2	CC₅₀	10.71 μM Compound: LONAFARNIB	Toxicity against Caco-2 cells determined at 48 hours by intracellular ATP concentration using the CellTiter-Glo Luminescent Cell Viability Assay Toxicity against Caco-2 cells determined at 48 hours by intracellular ATP concentration using the CellTiter-Glo Luminescent Cell Viability Assay	10.21203/rs.3.rs-23951/v1
Caco-2	IC₅₀	5.68 μM Compound: LONAFARNIB	Determination of IC50 values for inhibition of SARS-CoV-2 induced cytotoxicity of Caco-2 cells after 48 hours by high content imaging Determination of IC50 values for inhibition of SARS-CoV-2 induced cytotoxicity of Caco-2 cells after 48 hours by high content imaging	10.21203/rs.3.rs-23951/v1
COS-1	IC₅₀	75 nM Compound: 5	inhibition of tumor colony formation in soft agar inhibition of tumor colony formation in soft agar	[PMID: 10411485]
COS-7	IC₅₀	10 nM Compound: 15	Inhibiting the farnesylation of H-ras proteins in COS-7 monkey cells transiently expressing H-ras[Val12]-CVLS in the whole cell assay. Inhibiting the farnesylation of H-ras proteins in COS-7 monkey cells transiently expressing H-ras[Val12]-CVLS in the whole cell assay.	[PMID: 9822558]
COS-7	IC₅₀	10 nM Compound: 9b	Inhibition of FTase in human COS7 cells Inhibition of FTase in human COS7 cells	[PMID: 20925433]
HCT-116	EC₅₀	74 nM Compound: SCH66336	Inhibition of anchorage-independent growth in human HCT-116 cells assessed as inhibition of colony formation in presence of 10% FBS Inhibition of anchorage-independent growth in human HCT-116 cells assessed as inhibition of colony formation in presence of 10% FBS	[PMID: 16222147]
HCT-116	EC₅₀	94 nM Compound: SCH66336	Inhibition of anchorage-independent growth in human HCT-116 cells assessed as inhibition of colony formation incubated for 14 days in presence of 10% FBS by imaging based soft agar colony formation assay Inhibition of anchorage-independent growth in human HCT-116 cells assessed as inhibition of colony formation incubated for 14 days in presence of 10% FBS by imaging based soft agar colony formation assay	[PMID: 16222147]
HCT-116	IC₅₀	0.07 μM Compound: 15	Compound was measured for inhibition of HCT116 tumor cell line in colon under soft agar assay. Compound was measured for inhibition of HCT116 tumor cell line in colon under soft agar assay.	[PMID: 9822558]
MCF7	IC₅₀	0.05 μM Compound: 15	Compound was measured for inhibition of MCF-7 tumor cell line in breast under soft agar assay. Compound was measured for inhibition of MCF-7 tumor cell line in breast under soft agar assay.	[PMID: 9822558]
NIH3T3	EC₅₀	0.16 μM Compound: 2, SCH-66336	Effective concentration against Ha-RAS processing in NIH3T3 ras-transformed cells Effective concentration against Ha-RAS processing in NIH3T3 ras-transformed cells	[PMID: 12657284]
NIH3T3	EC₅₀	100 nM Compound: Lonafarnib	Inhibition of Ras farnesylation in H-Ras transformed NIH3T3 cells Inhibition of Ras farnesylation in H-Ras transformed NIH3T3 cells	[PMID: 15454228]
NIH3T3	EC₅₀	50 nM Compound: SCH66336	Inhibition of anchorage-independent growth in H-Ras transformed mouse NIH3T3 cells assessed as inhibition of colony formation in presence of 10% bovine serum Inhibition of anchorage-independent growth in H-Ras transformed mouse NIH3T3 cells assessed as inhibition of colony formation in presence of 10% bovine serum	[PMID: 16222147]
NIH3T3	EC₅₀	56 nM Compound: SCH66336	Inhibition of anchorage-independent growth in H-Ras transformed mouse NIH3T3 cells assessed as inhibition of colony formation incubated for 14 days in presence of 10% bovine serum by imaging based soft agar colony formation assay Inhibition of anchorage-independent growth in H-Ras transformed mouse NIH3T3 cells assessed as inhibition of colony formation incubated for 14 days in presence of 10% bovine serum by imaging based soft agar colony formation assay	[PMID: 16222147]
NIH3T3	IC₅₀	2.7 μM Compound: SCH66336	TP_TRANSPORTER: inhibition of DNR efflux (DNR: ? uM) in MDR1-expressing NIH3T3 cells TP_TRANSPORTER: inhibition of DNR efflux (DNR: ? uM) in MDR1-expressing NIH3T3 cells	[PMID: 11606389]
NIH3T3	IC₅₀	500 μM Compound: SCH-66336	Inhibition of K-Ras transformed NIH3T3 cell proliferation Inhibition of K-Ras transformed NIH3T3 cell proliferation	[PMID: 15501065]
NIH3T3	IC₅₀	72 μM Compound: SCH-66336	Inhibition of H-Ras transformed NIH3T3 cell proliferation Inhibition of H-Ras transformed NIH3T3 cell proliferation	[PMID: 15501065]
NIH-H	IC₅₀	72 nM Compound: 15	Compound ability to inhibit anchorage-independent growth of NIH-H tumor cell lines in soft agar. Compound ability to inhibit anchorage-independent growth of NIH-H tumor cell lines in soft agar.	[PMID: 9822558]
NIH-K	IC₅₀	500 nM Compound: 15	Compound ability to inhibit anchorage-independent growth of NIH-K tumor cell lines in soft agar. Compound ability to inhibit anchorage-independent growth of NIH-K tumor cell lines in soft agar.	[PMID: 9822558]

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].

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

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].

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

Clinical Trial

NCT Number	Sponsor	Condition	Start Date	Phase A549
NCT01329991	Plexxikon\|		2011-05	PHASE1

Chemical Information

CAS No. 193275-84-2
Appearance Solid
Molecular Weight 638.82
Formula C₂₇H₃₁Br₂ClN₄O₂
Color White to off-white
SMILES

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

Sch66336
Shipping

Room temperature in continental US; may vary elsewhere.

Storage

Powder	-20°C	3 years
	4°C	2 years
In solvent	-80°C	2 years
	-20°C	1 year

Publications (14)

All IFWBHistological Imaging/StainingRT-PCR

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Journal Impact Factor

Nat Commun

Targeting NRAS via miR-1304-5p or farnesyltransferase inhibition confers sensitivity to ALK inhibitors in ALK-mutant neuroblastoma. [Abstract]

2024 Apr 23;15(1):3422. PMID: 38653965

Lonafarnib purchased from MedChemExpress. Usage Cited in: Nat Commun. 2024 Apr 23;15(1):3422. [Abstract]

Immunohistochemistry (pERK) in tumours from NSG mice treated with Lonafarnib (10 μL/g; p.o.; once daily). Lonafarnib led to a profound decrease in pERK expression levels.
Nat Commun

Recapitulation of HDV infection in a fully permissive hepatoma cell line allows efficient drug evaluation. [Abstract]

2019 May 22;10(1):2265. PMID: 31118422

Lonafarnib purchased from MedChemExpress. Usage Cited in: Nat Commun. 2019 May 22;10(1):2265. [Abstract]

Lonafarnib (1.8 μM) treatment resulted in significant and selective increase in intracellular L-HDAg of HepNB2.7 cells.

Lonafarnib purchased from MedChemExpress. Usage Cited in: Nat Commun. 2019 May 22;10(1):2265. [Abstract]

Lonafarnib (1.8 μM) treatment caused an eightfold increase of intracellular L-HDAg in HepNB2.7 cells compared with the untreated controls, while the levels of S-HDAg only marginally (1.6-fold) increased.

Lonafarnib purchased from MedChemExpress. Usage Cited in: Nat Commun. 2019 May 22;10(1):2265. [Abstract]

Lonafarnib (1.8 μM) treatment led to a twofold increase in the total intracellular HDV genomes.

Lonafarnib purchased from MedChemExpress. Usage Cited in: Nat Commun. 2019 May 22;10(1):2265. [Abstract]

Quantitative PCR on intracellular HDV replicative intermediates and the two markers for IFN induction (IFN-λ and RSAD2) was performed. Lonafarnib (1.8 μM) profoundly increased the intracellular HDV replication and the induction of IFN responses in PHH co-infected with HDV and HBV.
Adv Sci (Weinh)

Multimodal Investigation of Angiogenesis and Its Prevention by Small Compounds in a Zebrafish Cancer Model. [Abstract]

2025 Jun 25:e15176. PMID: 40557748
J Clin Invest

Cancer-associated SPOP mutations enlarge nuclear size and facilitate nuclear envelope rupture upon farnesyltransferase inhibitor treatment. [Abstract]

2025 Jul 15;135(14):e189048. PMID: 40662365
Int J Biol Sci

FKBP10 Promotes the Muscle Invasion of Bladder Cancer via Lamin A Dysregulation. [Abstract]

2025 Jan 1;21(2):758-771. PMID: 39781460
Cell Death Dis

Activation of AKT via a dual mechanism enhances the susceptibility of melanoma cells to glucose deprivation. [Abstract]

2025 Aug 7;16(1):595. PMID: 40774947
Phytomedicine

Astragaloside IV protects against lung injury and pulmonary fibrosis in COPD by targeting GTP-GDP domain of RAS and downregulating the RAS/RAF/FoxO signaling pathway. [Abstract]

2023 Nov:120:155066. PMID: 37690229
Aging Cell

Transient introduction of human telomerase mRNA improves hallmarks of progeria cells. [Abstract]

2019 Aug;18(4):e12979. PMID: 31152494
Eur J Pharmacol

Heat stroke-induced structural and functional impairments of cognition-relevant brain areas in mice is associated with alpha-7 nicotinic acetylcholine receptors downregulation. [Abstract]

2026 Mar 28:1019:178723. PMID: 41786068
Virol Sin

Identification of a receptor tyrosine kinase inhibitor CP-724714 inhibits SADS-CoV related swine diarrhea coronaviruses infection in vitro. [Abstract]

2023 Oct;38(5):778-786. PMID: 37406816
J Neurosci

Ras Inhibitor Lonafarnib Rescues Structural and Functional Impairments of Synapses of Aβ1-42 Mice via α7nAChR-Dependent BDNF Upregulation. [Abstract]

2022 Aug 3;42(31):6090-6107. PMID: 35760529
Sci Rep

Generation and characterization of a stable cell line persistently replicating and secreting the human hepatitis delta virus. [Abstract]

2019 Jul 10;9(1):10021. PMID: 31292511
J Virol

Molecular mechanism of resistance to lonafarnib conferred by mutations in the cysteine-rich region of respiratory syncytial virus fusion glycoprotein and discovery of a lonafarnib-derived antiviral PROTAC. [Abstract]

2025 Dec 9:e0148725. PMID: 41364004
Med Mycol

Lonafarnib synergizes with azoles against Aspergillus spp. and Exophiala spp. [Abstract]

2018 Jun 1;56(4):452-457. PMID: 29420769

Solvent & Solubility

In Vitro:

DMSO : 25 mg/mL (39.13 mM; ultrasonic and warming and heat to 60°C; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)

View the Complete Stock Solution Preparation Table

Preparing Stock Solutions

View the Complete Stock Solution Preparation Table

Concentration Solvent Mass

1 mg

5 mg

10 mg

Concentration

Solvent

Mass

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. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.

Storage method and period of stock solution: -80°C, 2 years; -20°C, 1 year. When stored at -80°C, please use it within 2 years. When stored at -20°C, please use it within 1 year.

Molarity Calculator

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

Mass Mass

Concentration Concentration

Volume Volume

Molecular Weight Molecular Weight

Dilution Calculator

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

Concentration _(start) Concentration _(start)

Volume _(start) Volume _(start)

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In Vivo:

Select the appropriate dissolution method based on your experimental animal and administration route.

Stock Solution Working Solution

For the following dissolution methods, please ensure to first prepare a clear stock solution using an In Vitro approach and then sequentially add co-solvents:
To ensure reliable experimental results, the clarified stock solution can be appropriately stored based on storage conditions. As for the working solution for In Vivo experiments, it is recommended to prepare freshly and use it on the same day.
The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.

Protocol 1

Add each solvent one by one: 10% DMSO 40% PEG300 5% Tween-80 45% Saline

Solubility: ≥ 2.5 mg/mL (3.91 mM); Clear solution

This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown).

Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 400 μL PEG300, and mix evenly; then add 50 μL Tween-80 and mix evenly; then add 450 μL Saline to adjust the volume to 1 mL.

Protocol 2

Add each solvent one by one: 10% DMSO 90% (20% SBE-β-CD in Saline)

Solubility: ≥ 2.5 mg/mL (3.91 mM); Clear solution

This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown).

Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 900 μL 20% SBE-β-CD in Saline, and mix evenly.

Protocol 3

Add each solvent one by one: 10% DMSO 90% Corn Oil

Solubility: ≥ 2.5 mg/mL (3.91 mM); Clear solution

This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown). If the continuous dosing period exceeds half a month, please choose this protocol carefully.

Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 900 μL Corn oil, and mix evenly.

In Vivo Dissolution Calculator

Please enter the basic information of animal experiments:

Dosage Dosage
mg/kg
Animal Weight (Per Animal) Animal Weight (Per Animal)
g
Dosing Volume (Per Animal) Dosing Volume (Per Animal)
μL
Number of Animals Number of Animals

Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.

Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.

Please enter your animal formula composition:

%
DMSO +

Recommended: Keep the proportion of DMSO in working solution below 2% if your animal is weak.
%
+
+
%
Tween-80 + +
%
Saline +

The co-solvents required include: DMSO, . All of co-solvents are available by MedChemExpress (MCE). , Tween 80. All of co-solvents are available by MedChemExpress (MCE).

Working solution concentration: 0.22 mg/mL

Protocol

Kinase Assay^[1]

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

MedChemExpress (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].

MedChemExpress (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.

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

Purity & Documentation

Select Batch:

Purity: 99.98%

Assay: 99.98%

ee.: 99.98%

Data Sheet (283 KB)
SDS (396 KB)
- English - EN (396 KB)
- Français - FR (396 KB)
- Deutsch - DE (396 KB)
- Norwegian - NO (396 KB)
- Español - ES (396 KB)
- Swedish - SV (396 KB)
- Italian - IT (396 KB)
- Portuguese - PT (396 KB)
COA (2659 KB)
Elemental Analysis Report (2659 KB)
HNMR (2659 KB)
CNMR (2659 KB)
RP-HPLC (2659 KB)
NP-HPLC (2659 KB)
MS (2659 KB)
LCMS (2659 KB)
IR (2659 KB)
GC (2659 KB)
OR (2659 KB)
SDS-PAGE (2659 KB)
SEC-HPLC (2659 KB)
Other Report (2659 KB)
Handling Instructions (2659 KB)

References

[1]. Liu M, et al. Antitumor activity of SCH 66336, an orally bioavailable tricyclic inhibitor of farnesyl protein transferase, in human tumor xenograft models and wap-ras transgenic mice. Cancer Res. 1998 Nov 1;58(21):4947-56. [Content Brief]

[2]. Chaponis D, et al. Lonafarnib (SCH66336) improves the activity of temozolomide and radiation for orthotopic malignant gliomas. J Neurooncol. 2011 Aug;104(1):179-89. [Content Brief]

[3]. Koh C,et al. Oral prenylation inhibition with lonafarnib in chronic hepatitis D infection: a proof-of-concept randomised, double-blind, placebo-controlled phase 2A trial. Lancet Infect Dis. 2015 Oct;15(10):1167-1174. [Content Brief]

[4]. Hernandez I, et al. A farnesyltransferase inhibitor activates lysosomes and reduces tau pathology in mice with tauopathy. Sci Transl Med. 2019 Mar 27;11(485):eaat3005. [Content Brief]

Help & FAQs

How should lyophilized recombinant proteins be reconstituted and stored?

1. Before opening the cap, centrifuge the vial at 13000 rpm for 20-30 seconds. This step will ensure that any lyophilized powder that may have adhered to the cap or walls is collected at the bottom of the vial, minimizing the risk of product loss.

Complete Stock Solution Preparation Table

Storage method and period of stock solution: -80°C, 2 years; -20°C, 1 year. When stored at -80°C, please use it within 2 years. When stored at -20°C, please use it within 1 year.

Optional Solvent	Concentration Solvent Mass	1 mg	5 mg	10 mg	25 mg
DMSO	1 mM	1.5654 mL	7.8269 mL	15.6539 mL	39.1347 mL
	5 mM	0.3131 mL	1.5654 mL	3.1308 mL	7.8269 mL
	10 mM	0.1565 mL	0.7827 mL	1.5654 mL	3.9135 mL
	15 mM	0.1044 mL	0.5218 mL	1.0436 mL	2.6090 mL
	20 mM	0.0783 mL	0.3913 mL	0.7827 mL	1.9567 mL
	25 mM	0.0626 mL	0.3131 mL	0.6262 mL	1.5654 mL
	30 mM	0.0522 mL	0.2609 mL	0.5218 mL	1.3045 mL

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Lonafarnib

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Publications Citing Use of MedChemExpress (MCE) Lonafarnib

All Ras Isoforms

Biological Activity

Chemical Information

Publications (14)

Solvent & Solubility

Protocol

Purity & Documentation

References

Help & FAQs

Complete Stock Solution Preparation Table

Lonafarnib Related Classifications

Cat. No.: HY-15136