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Chemical Structure| 193275-84-2 Chemical Structure| 193275-84-2
Chemical Structure| 193275-84-2

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CAS No.: 193275-84-2

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Lonafarnib is a FPTase inhibitor. It can inhibit H-ras (IC50 = 1.9 nM), K-ras-4B (IC50 = 5.2 nM) and N-ras (IC50 = 2.8 nM).

Synonyms: Sch66336; Sarasar

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Product Details of Lonafarnib

CAS No. :193275-84-2
Formula : C27H31Br2ClN4O2
M.W : 638.82
SMILES Code : O=C(N1CCC(CC(N2CCC([C@@H]3C4=C(Br)C=C(Cl)C=C4CCC5=CC(Br)=CN=C53)CC2)=O)CC1)N
Synonyms :
Sch66336; Sarasar
MDL No. :MFCD06795138
InChI Key :DHMTURDWPRKSOA-RUZDIDTESA-N
Pubchem ID :148195

Safety of Lonafarnib

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H315-H319-H335
Precautionary Statements:P261-P305+P351+P338

Related Pathways of Lonafarnib

GPCR

Isoform Comparison

Biological Activity

Target
  • Transferase

    K-ras-4B, IC50:2.8 nM

    H-ras, IC50:1.9 nM

In Vitro:

Cell Line
Concentration Treated Time Description Reference
normal human dermal fibroblasts (NDFs) 5 μM 16 days To investigate the effect of FTI-277 on progerin accumulation, results showed that FTI-277 significantly reduced progerin accumulation. PMC11113360
C2C12 myotubes 2 μM 24 hours Lonafarnib significantly improved myotube area, fusion index, and myotube diameter, indicating its protective effect against dexamethasone-induced muscle atrophy. PMC11696026
HEp-2 cells 5 μM 48 hours To screen the ReFRAME library and confirm the antiviral activity of Lonafarnib PMC10853176
293 T cells 5 μM 48 hours To evaluate the inhibitory effect of Lonafarnib on RSV F protein-induced cell fusion PMC10853176
MCF-7 5 and 10 μM 48 hours To observe the effects of lonafarnib on microtubule structure, results showed that lonafarnib treatment led to increased microtubule bundling PMC1861827
A549 5-20 μM 48 hours To assess the effects of lonafarnib on tubulin polymerization, results showed that lonafarnib treatment led to increased tubulin polymerization PMC1861827
HEp-2 cells 57.7 ± 15.4 nM ( EC50) 72 hours Lonafarnib inhibited RSV A2 and B01 genotypes with EC50 values of 57.7 ± 15.4 nM and 75.5 ± 4.0 nM, respectively. PMC11163014
Human bronchial epithelial cells (HBEC) 599.9 ± 67.4 nM ( EC50) 72 hours Lonafarnib inhibited RSV A2 and B01 replication in HBEC with EC50 values of 599.9 ± 67.4 nM and 515.0 ± 44.2 nM, respectively. PMC11163014
SH-SY5Y 1 μM 72 hours Lonafarnib in combination with ALK TKIs decreased cell viability and showed synergistic effects at higher concentrations PMC11039739
KELLY 1 μM 72 hours Lonafarnib in combination with ALK TKIs showed synergistic effects in KELLY cells, but additive effects at higher concentrations PMC11039739

In Vivo:

Species
Animal Model
Administration Dosage Frequency Description Reference
Mice RSV infection model Oral 60 mg/kg twice daily for 4 days To evaluate the effect of Lonafarnib on RSV virus load in mice, results showed that Lonafarnib significantly reduced the virus load PMC10853176
BALB/c mice RSV infection model Oral 17 or 34 mg/kg Twice daily for 4 consecutive days Lonafarnib significantly reduced RSV replication in the BALB/c mouse model, with a 7.4-fold decrease in viral titer at 34 mg/kg dose, and alleviated lung inflammation. PMC11163014
NSG mice COG-N-426x PDX model Oral 40 mg/kg Daily for 30 days Combination of lonafarnib with ceritinib significantly delayed tumor growth and showed strong synergistic effects during treatment, but tumors rapidly regrew after cessation of therapy PMC11039739
Sprague-Dawley rats Dexamethasone-induced muscle atrophy model Intraperitoneal injection 1 μM and 5 μM Once daily for 6 days Lonafarnib significantly improved grip strength, muscle weight, and compound muscle action potential (CMAP) amplitudes in dexamethasone-induced muscle atrophy models, indicating its mitigation of muscle atrophy through enhanced mitochondrial function and anabolic pathways. PMC11696026
Mice LmnaG609G/G609G mouse model Oral 450 mg/kg Daily, throughout the survival period To evaluate the effect of Lonafarnib on LmnaG609G/G609G mice, it was found to extend survival, improve body weight, and reduce kyphosis PMC11488313
Mice Hutchinson-Gilford progeria syndrome model Oral 450 mg/kg Daily, from post-weaning (P21) or P100 to P168 days Lonafarnib improved cardiovascular function and survival, significantly reducing pulse wave velocity and improving left ventricular diastolic function. PMC10023154

Clinical Trial:

NCT Number Conditions Phases Recruitment Completion Date Locations
NCT00040534 Neoplasms Phase 1 Terminated - -
NCT00040547 Neoplasms Phase 1 Completed - -
NCT00003956 Lymphoma Unsp... More >>ecified Adult Solid Tumor, Protocol Specific Less << Phase 1 Completed - United States, New York ... More >> Memorial Sloan-Kettering Cancer Center New York, New York, United States, 10021 Less <<
NCT00038493 Glioblastoma Multiforme Phase 2 Completed - United States, Texas ... More >> UTMD Anderson Cancer Center Houston, Texas, United States, 77030 Less <<
NCT00038584 Carcinoma, Squamous Cell ... More >> Cancer of Head and Neck Less << Phase 1 Completed - United States, Texas ... More >> The University of Texas M. D. Anderson Cancer Center Houston, Texas, United States, 77030 Less <<
NCT00034684 Leukemia Myel... More >>odysplastic Syndromes Leukemia, Myeloid, Chronic Blast Crisis Leukemia, Lymphocytic Less << Phase 1 Phase 2 Completed - -
NCT00038597 Myelogenous Leukemia, Chronic Phase 2 Completed - United States, Texas ... More >> MDAnderson Cancer Center Houston, Texas, United States, 77030 Less <<
NCT00073450 Carcinoma, Squamous Cell ... More >> Head and Neck Neoplasms Less << Phase 2 Terminated - -
NCT00612651 Gliosarcoma G... More >>lioblastoma Anaplastic Astrocytoma Less << Phase 1 Completed - United States, North Carolina ... More >> Duke University Health System Durham, North Carolina, United States, 27710 Less <<
NCT00020774 Liver Cancer Phase 2 Withdrawn - -
NCT00006351 Bladder Cancer ... More >> Transitional Cell Cancer of the Renal Pelvis and Ureter Urethral Cancer Less << Phase 2 Completed - Netherlands ... More >> University Medical Center Nijmegen Nijmegen, Netherlands, 6500 Less <<
NCT00068757 Breast Cancer Phase 1 Completed - Belgium ... More >> Institut Jules Bordet Brussels, Belgium, 1000 France Institut Curie Hopital Paris, France, 75248 Netherlands Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital Amsterdam, Netherlands, 1066 CX Less <<
NCT03719313 Hepatitis Delta Virus Phase 3 Not yet recruiting November 1, 2021 -
NCT00005030 Colorectal Cancer ... More >> Metastatic Cancer Less << Phase 1 Withdrawn(No enrollment.) - -
NCT00083096 Brain and Central Nervous Syst... More >>em Tumors Less << Phase 1 Unknown - France ... More >> Centre de Lutte Contre le Cancer Georges-Francois Leclerc Dijon, France, 21079 Centre Regional Rene Gauducheau Nantes-Saint Herblain, France, 44805 Switzerland Centre Hospitalier Universitaire Vaudois Lausanne, Switzerland, CH-1011 Less <<
NCT00050336 Carcinoma, Non-small-cell Lung... More >> Metastases, Neoplasm Less << Phase 3 Terminated - -
NCT00102635 Head and Neck Cancer Phase 1 Terminated(Slow accrual.) - United States, Texas ... More >> UT MD Anderson Cancer Center Houston, Texas, United States, 77030 Less <<
NCT03600714 Liver Disease ... More >> Hepatitis D Less << Phase 2 Recruiting December 31, 2025 United States, Maryland ... More >> National Institutes of Health Clinical Center Recruiting Bethesda, Maryland, United States, 20892 Contact: For more information at the NIH Clinical Center contact Office of Patient Recruitment (OPR) ?? 800-411-1222 ext TTY8664111010 ?? prpl@cc.nih.gov Less <<
NCT02511431 Hepatitis D Phase 2 Completed - United States, Maryland ... More >> National Institutes of Health Clinical Center, 9000 Rockville Pike Bethesda, Maryland, United States, 20892 Less <<
NCT00281515 Epithelial Ovarian Cancer PHASE2 COMPLETED 2025-12-11 Charité - Universit?tsmedizin ... More >>Berlin, Campus Virchow-Klinikum, Klinik für Frauenheilkunde, Berlin, 13353, Germany|Klinikum Bremen Mitte, Frauenklinik, Bremen, 28177, Germany|Carl-Gustav-Carus der TU Dresden, Universit?ts-Frauenklinik, Dresden, 01307, Germany|Ev. Krankenhaus, Frauenklinik, Düsseldorf, 40217, Germany|Klinik für Frauenheilkunde der Univ. Erlangen, Erlangen, 91054, Germany|Universit?tsfrauenklinik, Essen, 45147, Germany|Klinikum der Johann Wolfgang Goethe Universit?t, Klinik für Frauenheilkunde u. Geburtshilfe, Frankfurt, 60590, Germany|Universit?tsklinikum Freiburg, Frauenklinik, Freiburg, 79106, Germany|Kreiskrankenhaus, Frauenklinik, Gifhorn, 38518, Germany|Klinik u. Poliklinik für Gyn?kologie und Geburtshilfe, Greifswald, 17487, Germany|Medizinische Hochschule, Hannover, 30625, Germany|St. Vincentius-Krankenh?user, Karlsruhe, 76137, Germany|Universit?tsklinikum Schleswig-Holstein, Campus Kiel, Klinik für Gyn?kologie und Geburtshilfe, Kiel, 24105, Germany|Klinik der Otto-von-Guericke Universit?t, Frauenklinik, Magdeburg, 39108, Germany|Johannes-Gutenberg-Universit?t, Universit?ts-Frauenklinik, Mainz, 55101, Germany|Klinikum der Philipps-Universit?t Marburg, Klinik für Gyn?kologie, Gyn?kologische Endokrinologie, Marburg, 35037, Germany|Klinikum Gro?hadern, Frauenklinik, München, 81377, Germany|Klinikum rechts der Isar der TU München, München, 81675, Germany|Elblandkliniken, Frauenklinik, Radebeul, 01445, Germany|Klinikum Südstadt, Rostock, 18059, Germany|Universit?ts-Frauenklinik, Tübingen, 72076, Germany|Universit?tsfrauenklinik, Ulm, 89075, Germany|Dr. Horst Schmidt Klinik, Gyn?kologie u. Gyn?kologische Onkologie, Wiesbaden, 65199, Germany Less <<
NCT02511431 - Completed - -
NCT00015899 Brain and Central Nervous Syst... More >>em Tumors Less << Phase 1 Completed - United States, California ... More >> UCSF Comprehensive Cancer Center San Francisco, California, United States, 94143-0372 United States, District of Columbia Children's National Medical Center Washington, District of Columbia, United States, 20010-2970 United States, Massachusetts Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute Boston, Massachusetts, United States, 02115 United States, North Carolina Duke Comprehensive Cancer Center Durham, North Carolina, United States, 27710 United States, Pennsylvania Children's Hospital of Philadelphia Philadelphia, Pennsylvania, United States, 19104-4318 Children's Hospital of Pittsburgh Pittsburgh, Pennsylvania, United States, 15213 United States, Tennessee St. Jude Children's Research Hospital Memphis, Tennessee, United States, 38105-2794 United States, Texas Texas Children's Cancer Center Houston, Texas, United States, 77030-2399 United States, Washington Children's Hospital and Regional Medical Center - Seattle Seattle, Washington, United States, 98105 Less <<
NCT00288444 Lung Cancer S... More >>oft Tissue Sarcoma Colorectal Carcinoma Breast Cancer Prostate Cancer Less << Phase 1 Terminated - United States, Georgia ... More >> Emory University Winship Cancer Institute Atlanta, Georgia, United States, 30308 Less <<
NCT00102648 Malignant Supratentorial Neopl... More >>asm Recurrent Glioblastoma Recurrent Gliosarcoma Less << Phase 1 Active, not recruiting December 1, 2020 United States, Texas ... More >> M D Anderson Cancer Center Houston, Texas, United States, 77030 Less <<
NCT01232881 - Terminated(funding terminated) - United States, Indiana ... More >> Indiana University Melvin and Bren Simon Cancer Center Indianapolis, Indiana, United States, 46202 Less <<
NCT00916747 Progeria Phase 2 Enrolling by invitation July 2020 United States, Massachusetts ... More >> Children's Hospital Boston Boston, Massachusetts, United States, 02115 Less <<
NCT02430181 Chronic Hepatitis D Infection Phase 2 Completed - Turkey ... More >> Ankara University Medical School Ankara, Turkey Less <<
NCT00047502 Chronic Myelogenous Leukemia Phase 1 Completed - United States, Texas ... More >> M.D. Anderson Cancer Center Houston, Texas, United States, 77030 Less <<
NCT01495585 Hepatitis D Phase 2 Completed - United States, Maryland ... More >> National Institutes of Health Clinical Center, 9000 Rockville Pike Bethesda, Maryland, United States, 20892 Less <<
NCT01495585 - Completed - -
NCT00081510 Breast Cancer Phase 2 Completed - -
NCT02968641 Chronic Delta Hepatitis Phase 2 Unknown - -
NCT02430194 Chronic Hepatitis D Infection Phase 2 Completed - Turkey ... More >> Ankara University Medical School Ankara, Turkey Less <<
NCT00539968 Prostate Cancer ... More >> Breast Cancer Ovarian Cancer Lung Cancer Gastric Cancer Less << Phase 1 Phase 2 Terminated - -
NCT00425607 Progeria|Hutchinson-Gilford Sy... More >>ndrome Less << PHASE2 COMPLETED 2025-10-09 Children's Hospital Boston, Bo... More >>ston, Massachusetts, 02115, United States Less <<
NCT00879034 Progeria Hutc... More >>hinson-Gilford Syndrome Less << Phase 2 Completed - United States, Massachusetts ... More >> Children's Hospital Boston Boston, Massachusetts, United States, 02115 Less <<
NCT00109538 Myelodysplastic Syndromes ... More >> Leukemia, Myelomonocytic, Chronic Myelodysplasia Myelomonocytic Less << Phase 3 Terminated - -
NCT00773474 Metastatic Breast Cancer PHASE2 TERMINATED 2025-11-10 Medical & Surgical Specialists... More >>, LLC, Galesburg, Illinois, 61401, United States|Cancer Care Center of Southern Indiana, Bloomington, Indiana, 47403, United States|Indiana University Melvin and Bren Simon Cancer Center, Indianapolis, Indiana, 46202, United States|Arnett Cancer Care, Lafayette, Indiana, 47904, United States|Horizon Oncology Center, Lafayette, Indiana, 47905, United States|Ireland Cancer Center - University Hospitals of Cleveland, Cleveland, Ohio, 44106, United States Less <<
NCT00425607 Progeria|Hutchinson-Gilford Sy... More >>ndrome Less << PHASE2 COMPLETED 2025-10-09 Children's Hospital Boston, Bo... More >>ston, Massachusetts, 02115, United States Less <<
NCT00773474 Metastatic Breast Cancer PHASE2 TERMINATED 2025-11-10 Medical & Surgical Specialists... More >>, LLC, Galesburg, Illinois, 61401, United States|Cancer Care Center of Southern Indiana, Bloomington, Indiana, 47403, United States|Indiana University Melvin and Bren Simon Cancer Center, Indianapolis, Indiana, 46202, United States|Arnett Cancer Care, Lafayette, Indiana, 47904, United States|Horizon Oncology Center, Lafayette, Indiana, 47905, United States|Ireland Cancer Center - University Hospitals of Cleveland, Cleveland, Ohio, 44106, United States Less <<
NCT00879034 - Completed - -
NCT02527707 Chronic Delta Hepatitis Phase 2 Completed - -
NCT02579044 Progeria Phase 1 Phase 2 Recruiting December 2021 United States, Massachusetts ... More >> Boston Children's Hospital Recruiting Boston, Massachusetts, United States, 02115 Contact: Monica E Kleinman, MD ?? ?? monica.kleinman@childrens.harvard.edu Less <<
NCT03895528 Progeria|HGPS APPROVED_FOR_MARKETING - -

Protocol

Bio Calculators
Preparing Stock Solutions 1mg 5mg 10mg

1 mM

5 mM

10 mM

1.57mL

0.31mL

0.16mL

7.83mL

1.57mL

0.78mL

15.65mL

3.13mL

1.57mL

Dissolving Methods
Please choose the appropriate dissolution scheme according to your animal administration guide.For the following dissolution schemes, clear stock solution should be prepared according to in vitro experiments, and then cosolvent should be added in turn:

in order to ensure the reliability of the experimental results, the clarified stock solution can be properly preserved according to the storage conditions; The working fluid for in vivo experiment is recommended to be prepared now and used on the same day;

The percentage shown in front of the following solvent refers to the volume ratio of the solvent in the final solution; If precipitation or precipitation occurs in the preparation process, it can be assisted by heating and/or ultrasound.
Protocol 1
Protocol 2

References

 

Historical Records

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