Synonyms: SCH 66336 | SCH-66336 | SCH66336 | Zokinvy®
lonafarnib is an approved drug (FDA (2020), EMA (2022))
Compound class:
Synthetic organic
Comment: Lonafarnib is an orally bioavailable molecule which inhibits farnesyl protein transferase, an enzyme that is responsible for catalysing the transfer of a 15-carbon isoprenoid group to a variety of cellular proteins including RAS [7].
![]() Ligand Activity Visualisation ChartsThese are box plot that provide a unique visualisation, summarising all the activity data for a ligand taken from ChEMBL and GtoPdb across multiple targets and species. Click on a plot to see the median, interquartile range, low and high data points. A value of zero indicates that no data are available. A separate chart is created for each target, and where possible the algorithm tries to merge ChEMBL and GtoPdb targets by matching them on name and UniProt accession, for each available species. However, please note that inconsistency in naming of targets may lead to data for the same target being reported across multiple charts. ✖ |
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References |
1. Downward J. (2003)
Targeting RAS signalling pathways in cancer therapy. Nat Rev Cancer, 3 (1): 11-22. [PMID:12509763] |
2. Gordon LB, Kleinman ME, Massaro J, D'Agostino Sr RB, Shappell H, Gerhard-Herman M, Smoot LB, Gordon CM, Cleveland RH, Nazarian A et al.. (2016)
Clinical Trial of the Protein Farnesylation Inhibitors Lonafarnib, Pravastatin, and Zoledronic Acid in Children With Hutchinson-Gilford Progeria Syndrome. Circulation, 134 (2): 114-25. [PMID:27400896] |
3. Gordon LB, Kleinman ME, Miller DT, Neuberg DS, Giobbie-Hurder A, Gerhard-Herman M, Smoot LB, Gordon CM, Cleveland R, Snyder BD et al.. (2012)
Clinical trial of a farnesyltransferase inhibitor in children with Hutchinson-Gilford progeria syndrome. Proc Natl Acad Sci USA, 109 (41): 16666-71. [PMID:23012407] |
4. Gordon LB, Shappell H, Massaro J, D'Agostino Sr RB, Brazier J, Campbell SE, Kleinman ME, Kieran MW. (2018)
Association of Lonafarnib Treatment vs No Treatment With Mortality Rate in Patients With Hutchinson-Gilford Progeria Syndrome. JAMA, 319 (16): 1687-1695. [PMID:29710166] |
5. Liu M, Bryant MS, Chen J, Lee S, Yaremko B, Lipari P, Malkowski M, Ferrari E, Nielsen L, Prioli N et al.. (1998)
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, 58 (21): 4947-56. [PMID:9810004] |
6. Moorthy NS, Sousa SF, Ramos MJ, Fernandes PA. (2013)
Farnesyltransferase inhibitors: a comprehensive review based on quantitative structural analysis. Curr Med Chem, 20 (38): 4888-923. [PMID:24059235] |
7. Taveras AG, Kirschmeier P, Baum CM. (2003)
Sch-66336 (sarasar) and other benzocycloheptapyridyl farnesyl protein transferase inhibitors: discovery, biology and clinical observations. Curr Top Med Chem, 3 (10): 1103-14. [PMID:12769711] |
8. Young SG, Yang SH, Davies BS, Jung HJ, Fong LG. (2013)
Targeting protein prenylation in progeria. Sci Transl Med, 5 (171): 171ps3. [PMID:23390246] |