Cell lines

UMSCC10B, UMSCC14B, UMSCC17B, UMSCC22B, UMSCC35 and UMSCC38 cells

Preparation method

The solubility of this compound in DMSO is >10 mM. General tips for obtaining a higher concentration: Please warm the tube at 37 ℃ for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below -20 ℃ for several months.

Reaction Conditions

0.1 ~ 8 μM; 24 hrs

Applications

In human head and neck squamous carcinoma cells (HNSCCs), SCH66336 (0.1 ~ 8 μM) suppressed cell growth and induced apoptosis of in a dose- and time- dependent manner.

Animal models

NOD/SCID mice bearing XEN08 tumors

Dosage form

50 mg/kg; p.o.; b.i.d., for 20 days

Applications

In NOD/SCID mice bearing XEN08 tumors, SCH66336 (50 mg/kg, p.o., b.i.d.) significantly inhibited tumor growth, with a mean growth inhibition of 63.8 ± 5.0%.

Other notes

Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal.

Lonafarnib (SCH66336, Sarasar) is an potent, selective, orally, bioavailable tricyclic nonpeptidyl nonsulfhydry inhibitor of farnesyltransferase (FTase).^[1]It is a small molecular with the formula of C₂₇H₃₁Br₂ClN₄O₂and molecular weight of 638.82. Farnesylated Ras proteins was found to regulate signal transduction pathways which drive cell proliferation, growth and survival and be required for its membrane localization.^{[1, 2]}Lonafarnib inhibits the post-translational farnesylcation of ras proteins, therefore blocking translocation of RAS to the plasma membrane.^[3]

Reference

[1] Eric W, Malcolm J. M, Kim N. C, D. Scott E, et al. A multinomial Phase II study of lonafarnib (SCH 66336) in patients with refractory urothelial cancer. Urologic Oncology: Seminars and Original Investigations. 2005, 23. 143-149.

[2] Gongjie L, Stacey A. T, Cindy H. M, Yunsheng H, W. Robert B, et al. Continuous and intermittent dosing of lonafarnib potentiates the therapeutic efficacy of docetaxel on preclinical human prostate cancer models. Int. J. Cancer. 2009, 125. 2711–2720.

[3] Vasiliki A. N, Alexander J. S, Keith T. F, Hensin T, et al. Melanoma: New Insights and New Therapies. J Invest Dermatol. 2012, 132. 854–863.