FTI-2148 diTFA is an inhibitor (blocker/antagonist) of RAS C-terminal modified farnesyl transferase (FT-1) and geranyl transferase 1 (GGT-1). The IC50 for inhibiting FT-1 and GGT-1 is 1.4 nM and 1.4 nM, respectively. 1.7 μM.

Physicochemical Properties

Molecular Formula	C24H28N4O3S.2C2HF3O2
Molecular Weight	680.62
Exact Mass	566.181
CAS #	817586-01-9
Related CAS #	FTI-2148;251577-09-0
PubChem CID	168011754
Appearance	Typically exists as solid at room temperature
Hydrogen Bond Donor Count	5
Hydrogen Bond Acceptor Count	11
Rotatable Bond Count	11
Heavy Atom Count	39
Complexity	691
Defined Atom Stereocenter Count	1
SMILES	CC1=CC=CC=C1C2=C(C=CC(=C2)CNCC3=CN=CN3)C(=O)N[C@@H](CCSC)C(=O)O.C(=O)(C(F)(F)F)O
InChi Key	ZCCUFUPJNUTGJM-FTBISJDPSA-N
InChi Code	InChI=1S/C24H28N4O3S.C2HF3O2/c1-16-5-3-4-6-19(16)21-11-17(12-25-13-18-14-26-15-27-18)7-8-20(21)23(29)28-22(24(30)31)9-10-32-2;3-2(4,5)1(6)7/h3-8,11,14-15,22,25H,9-10,12-13H2,1-2H3,(H,26,27)(H,28,29)(H,30,31);(H,6,7)/t22-;/m0./s1
Chemical Name	(2S)-2-[[4-[(1H-imidazol-5-ylmethylamino)methyl]-2-(2-methylphenyl)benzoyl]amino]-4-methylsulfanylbutanoic acid;2,2,2-trifluoroacetic acid
Synonyms	FTI2148 diTFA; FTI 2148 diTFA
HS Tariff Code	2934.99.9001
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)

Biological Activity

ln Vitro	In NIH3T3 cells transformed with all 3 RAS, FTI-2148 (30 μM) suppresses farnesylation of the single farnesylated protein, HDJ2 [1]. Against P. falciparum PFT, mammalian PFT, and mammalian PGGT-I, FTI-2148 diTFA has an IC50 of 15 nM, 0.82 nM, and 1700 nM, correspondingly. PGGT-I is geranylgeranyl transferase-I; PFT is protein farnesyl transferase[2].
ln Vivo	In human lung adenocarcinoma A-549 cells, FTI-2148 (ip; 25 or 50 mpk/day using minipump; start on day 15, pause on day 45, restart on days 53-83) suppresses tumors. mouse model with growth 91% stimulated [1]. In a human xenograft nude mouse model, FTI-2148 (subcutaneous injection; 25 mpk/day using minipump; 14 days) reduced tumor development by 77% at the conclusion of two weeks of treatment [1]. In a ras transgenic mouse model, FTI-2148 (subcutaneous injection; 100 mg/kg/day; 14 days) promotes breast tumor regression [3]. In mouse mammary tumors cultured in vivo, FTI-2148 (subcutaneous injection; 100 mg/kg/day; 4 days) suppresses 85-88% of FTase activity but not GGTase I enzyme activity [3].
Cell Assay	Western Blot Analysis[1] Cell Types: NIH3T3 cells transformed with KRAS HRAS and NRAS Tested Concentrations: 30 μM Incubation Duration: Experimental Results: Inhibition of prenylation of KRAS and NRAS.
Animal Protocol	Animal/Disease Models: Ras transgenic mouse model [3] Doses: 100 mg/kg/day Route of Administration: subcutaneous injection; 100 mg/kg/day; 14-day Experimental Results: The regression of breast cancer in mice was diminished by 87 ± 3%.
References	[1]. 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 Oc [2]. Carrico D, et al.In vitro and in vivo antimalarial activity of peptidomimetic protein farnesyltransferase inhibitors with improved membrane permeability.Bioorg Med Chem. 2004 Dec 15;12(24):6517-26. [3]. 3. 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.

Solubility Data

Solubility (In Vitro)

Ethanol : ~5 mg/mL (~7.35 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 0.5 mg/mL (0.73 mM) (saturation unknown) in 10% EtOH + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 5.0 mg/mL clear EtOH stock solution to 400 μL of PEG300 and mix evenly; then add 50 μL of Tween-80 to the above solution and mix evenly; then add 450 μL of normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 0.5 mg/mL (0.73 mM) (saturation unknown) in 10% EtOH + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 5.0 mg/mL clear EtOH stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Solubility in Formulation 3: ≥ 0.5 mg/mL (0.73 mM) (saturation unknown) in 10% EtOH + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 5.0 mg/mL clear EtOH stock solution to 900 μL of corn oil and mix evenly.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	1.4692 mL	7.3462 mL	14.6925 mL
	5 mM	0.2938 mL	1.4692 mL	2.9385 mL
	10 mM	0.1469 mL	0.7346 mL	1.4692 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.