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FTI-2148

Names

[ CAS No. ]:
251577-09-0

[ Name ]:
FTI-2148

[Synonym ]:
L-Methionine, N-[[5-[[(1H-imidazol-4-ylmethyl)amino]methyl]-2'-methyl[1,1'-biphenyl]-2-yl]carbonyl]-
N-[(5-{[(1H-Imidazol-4-ylmethyl)amino]methyl}-2'-methyl-2-biphenylyl)carbonyl]-L-methionine
N-[(5-{[(1H-imidazol-4-ylmethyl)amino]methyl}-2'-methylbiphenyl-2-yl)carbonyl]-L-methionine

Biological Activity

[Description]:

FTI-2148 is a RAS C-terminal mimetic dual farnesyl transferase (FT-1) and geranylgeranyl transferase-1 (GGT-1) inhibitor with IC50s of 1.4 nM and 1.7 μM for FT-1 and GGT-1, respectively[1].

[Related Catalog]:

Research Areas >> Cancer
Signaling Pathways >> Metabolic Enzyme/Protease >> Farnesyl Transferase

[Target]

IC50: 1.4 nM (FT-1); 1.7 μM (GGT-1)[1]


[In Vitro]

FTI-2148 (30 μM) inhibits the farnesylation of the exclusively farnesylated protein HDJ2 in all 3 RAS-transformed NIH3T3 cells. Western Blot Analysis[2] Cell Line: KRAS HRAS, and NRAS-transformed NIH3T3 cells  Concentration: 30 μM Incubation Time: Result: Inhibited the prenylation of KRAS and NRAS.

[In Vivo]

FTI-2148 (subcutaneous injection; 100 mg/kg/day; 14 days) results in breast tumor regression in a ras transgenic mouse model[1]. FTI-2148 (subcutaneous injection; 100 mg/kg/day; 4 days) results in 85–88% inhibition of FTase with no inhibition of GGTase I enzymatic activity in breast tumors from mice in vivo settings[1]. Animal Model: Ras transgenic mouse model[1] Dosage: 100 mg/kg/day Administration: Subcutaneous injection; 100 mg/kg/day; 14 days Result: Induced regression by 87 ± 3% of mammary carcinomas in mice.

[References]

[1]. Sun J, et al. Geranylgeranyltransferase I inhibitor GGTI-2154 induces breast carcinoma apoptosis and tumor regression in H-Ras transgenic mice.Cancer Res. 2003 Dec 15;63(24):8922-9.

[2]. Sun J, et al. Antitumor efficacy of a novel class of non-thiol-containing peptidomimetic inhibitors of farnesyltransferase and geranylgeranyltransferase I: combination therapy with the cytotoxic agents cisplatin, Taxol, and gemcitabine. Cancer Res. 1999 Oct 1;59(19):4919-26.

[3]. Kazi A, et al. Dual Farnesyl and Geranylgeranyl Transferase Inhibitor Thwarts Mutant KRAS-Driven Patient-Derived Pancreatic Tumors.Clin Cancer Res. 2019 Oct 1;25(19):5984-5996.

Chemical & Physical Properties

[ Density]:
1.3±0.1 g/cm3

[ Boiling Point ]:
730.1±60.0 °C at 760 mmHg

[ Molecular Formula ]:
C24H28N4O3S

[ Molecular Weight ]:
452.569

[ Flash Point ]:
395.4±32.9 °C

[ Exact Mass ]:
452.188202

[ LogP ]:
2.45

[ Vapour Pressure ]:
0.0±2.5 mmHg at 25°C

[ Index of Refraction ]:
1.626

Safety Information

[ Hazard Codes ]:
Xi

Related Compounds