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Purity: ≥98%
Lonafarnib (formerly SCH66336; SCH-66336; Sarasar; Zokinvy), a tricyclic derivative of carboxamide, is a novel, orally bioavailable and highly potent FPTase (farnesyl protein transferase) inhibitor with potential anticancer activity. It inhibits 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. Lonafarnib has been approved in 2020 to reduce the risk of death due to Hutchinson-Gilford progeria syndrome and for the treatment of certain processing-deficient progeroid laminopathies. It acts by binding to and inhibiting farnesyl transferase enzyme, which is involved in the post-translational modification and activation of Ras proteins. Ras proteins participate in numerous signalling pathways (proliferation, cytoskeletal organization), and play an important role in oncogenesis. Mutated ras proteins have been found in a wide range of human cancers.
| ln Vitro |
Lonafarnib (Sch66336) suppresses the transformed growth properties of human tumor cell lines carrying activated Ki-Ras proteins and potently inhibits Ha-Ras processing in whole cells[1]. When compared to the control treatment, all treatment groups that contained Lonafarnib (10 μM) had a noticeably greater amount of unfarnesylated H-Ras (116–137%)[2].
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| ln Vivo |
Lonafarnib (Sch66336) exhibits good oral bioavailability and pharmacokinetic characteristics in the mouse, rat, and monkey systems. Lonafarnib exhibits strong oral efficacy in a variety of human tumor xenograft models in the nude mouse, including tumors originating from the colon, lung, pancreatic, prostate, and urinary bladder[1]. In comparison to vehicle-treated control mice (T/C of 0.67), lionafarnib alone (80 mg/kg by oral gavage, once day) had a limited capacity to suppress orthotopic U87 tumors. The intended outcome of XRT/Tem (2.5 Gy/day for 2 days; 5 mg/kg by oral gavage 90 min before XRT) is a moderate in vivo suppression of tumor growth (T/C of 0.42). The strongest growth reduction (T/C of 0.02) and significant superiority over XRT/Tem (p<0.04) is achieved by concurrent administration of Lonafarnib/XRT/Tem (Lonafarnib 80 mg/kg by oral gavage, once daily, XRT 2.5 Gy/day for 2 days, and Tem 5 mg/kg by oral gavage 90 minutes prior to XRT). Most animals show a decrease in tumor volume (p<0.05) after 2 weeks and the effect persists after 4 weeks (p<0.05)[2].
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| 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.
[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. [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 |
| Molecular Formula |
C27H31BR2CLN4O2
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| Molecular Weight |
638.82
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| CAS # |
193275-84-2
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| Related CAS # |
(Rac)-Lonafarnib;193275-86-4
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| SMILES |
O=C(N1CCC(CC(N2CCC(C3C4=C(Br)C=C(Cl)C=C4CCC5=CC(Br)=CN=C53)CC2)=O)CC1)N
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| Synonyms |
Lonafarnib; SCH66336; Trade name: Sarasar; SCH 66336; SCH-66336;
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
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| Preparing Stock Solutions | 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 |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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