Lonafarnib|cas 193275-84-2|DC Chemicals|Price|Buy

Cas No.:	193275-84-2
Chemical Name:	1-Piperidinecarboxamide, 4-[2-[4-[(11R)-3,10-dibromo-8-chloro-6,11-dihydro-5H-benzo[5,6]cyclohepta[1,2-b]pyridin-11-yl]-1-piperidinyl]-2-oxoethyl]-
Synonyms:	SCH66336
SMILES:	O=C(N1CCC(CC(N2CCC([C@@H]3C4=C(Br)C=C(Cl)C=C4CCC5=CC(Br)=CN=C53)CC2)=O)CC1)N
Formula:	C₂₇H₃₁Br₂ClN₄O₂
M.Wt:	638.82
Sotrage:	2 years -20°C Powder, 2 weeks 4°C in DMSO, 6 months -80°C in DMSO

Description:	Lonafarnib is an orally bioavailable farnesyl protein transferase (FPTase) inhibitor for H-ras, K-ras and N-ras with IC50 of 1.9 nM, 5.2 nM and 2.8 nM, respectively.
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].
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].

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