Lonafarnib | CAS:193275-84-2

• 価格
• 構造式
• 製品情報
• 製品詳細
• 文献

価格

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構造式

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製品情報

Farnesyltransferase drives the post-translational farnesylation of a number of target proteins, including Ras, a component of the MAPK and Akt signaling pathways involved in cell proliferation, and Ras homolog enriched in brain (Rheb), which stimulates mTOR activity. By arresting growth, farnesyltransferase inhibitors have great potential as antitumor agents. Lonafarnib is a farnesyltransferase inhibitor that blocks the post-translational lipid modification of oncogenic Ras isoforms H-Ras, N-Ras, and K-Ras (IC₅₀s = 1.9, 2.8, and 5.2 nM, respectively) as well as Rheb (IC₅₀ = 10-100 nM). It inhibits H-Ras signaling in whole cells (IC₅₀ = 10 nM) and blocks the transformed growth properties of fibroblasts (IC₅₀ = 75 nM) and human tumor cell lines (IC₅₀ = 400 nM) expressing activated K-Ras proteins. In the nude mouse, lonafarnib demonstrates potent dose-dependent oral activity in an array of human tumor xenograft models including tumors originating from colon, lung, pancreas, prostate, and urinary bladder. Combination treatments with various cytotoxic agents (cyclophosphamide, 5-fluorouracil, and vincristine) or MAPK or Akt pathway inhibitors can enhance the in vivo efficacy of lonafarib.

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製品詳細

name	Lonafarnib
Formal Name	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]-1-piperidinecarboxamide
CAS Number	193275-84-2
Synonyms	Sarasar SCH 66336
Molecular Formula	C27H31Br2ClN4O2
Formula Weight	638.8
Purity	≥98%
Formulation	A crystalline solid
λmax	278 nm
SMILES	BrC1=CN=C([C@H](C2CCN(C(CC3CCN(C(N)=O)CC3)=O)CC2)C(C(Br)=CC(Cl)=C4)=C4CC5)C5=C1
InChI Code	InChI=1S/C27H31Br2ClN4O2/c28-20-12-19-2-1-18-13-21(30)14-22(29)24(18)25(26(19)32-15-20)17-5-9-33(10-6-17)23(35)11-16-3-7-34(8-4-16)27(31)36/h12-17,25H,1-11H2,(H2,31,36)/t25-/m1/s1
InChI Key	DHMTURDWPRKSOA-RUZDIDTESA-N
Storage	-20°C
Shipping	Room temperature in continental US; may vary elsewhere
Stability	≥ 2 years

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文献

1. Appels, N.M.G.M., Beijnen, J.H., and Schellens, J.H.M. Development of farnesyl transferase inhibitors: A review. Oncologist 10, 565-578 (2005).

2. Liu, M., Bryant, M.S., Chen, J., 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 Research 58, 4947-4956 (1998).

3. Basso, A.D., Mirza, A., Liu, G., et al. The farnesyl transferase inhibitor (FTI) SCH66336 (lonafarnib) inhibits Rheb farnesylation and mTOR signaling. Role in FTI enhancement of taxane and tamoxifen anti-tumor activity. The Journal of Biological Chemisty 280(35), 31101-31108 (2005).

4. Niessner, H., Beck, D., Sinnberg, T., et al. The farnesyl transferase inhibitor lonafarnib inhibits mTOR signaling and enforces sorafenib-induced apoptosis in melanoma cells. Journal of Investigative Dermatology 131(2), 468-479 (2011).

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