FGTI-2734 mesylate is an inhibitor (blocker/antagonist) of RAS C-terminal farnesyl transferase (FT) and geranyl transferase-1 (GGT), with IC50s of 250 nM and 520 nM for FT and GGT, respectively. FGTI-2734 mesylate can block the membrane localization of KRAS, thereby solving the problem of KRAS drug resistance and inhibiting mutant KRAS pancreatic tumors.

Physicochemical Properties

Molecular Formula	C27H35FN6O5S2
Molecular Weight	606.73240685463
Exact Mass	606.209
CAS #	2702297-24-1
Related CAS #	FGTI-2734;1247018-19-4
PubChem CID	145925655
Appearance	White to off-white solid powder
Hydrogen Bond Donor Count	1
Hydrogen Bond Acceptor Count	11
Rotatable Bond Count	10
Heavy Atom Count	41
Complexity	932
Defined Atom Stereocenter Count	0
SMILES	S(O)(=O)(=O)C.N(C1C=CC(C#N)=CC=1F)(CCN(CC1CCCCC1)S(C1N=CC=CC=1)(=O)=O)CC1=CN=CN1C
InChi Key	CVSSKDKRVCBPOV-UHFFFAOYSA-N
InChi Code	InChI=1S/C26H31FN6O2S.CH4O3S/c1-31-20-29-17-23(31)19-32(25-11-10-22(16-28)15-24(25)27)13-14-33(18-21-7-3-2-4-8-21)36(34,35)26-9-5-6-12-30-26;1-5(2,3)4/h5-6,9-12,15,17,20-21H,2-4,7-8,13-14,18-19H2,1H3;1H3,(H,2,3,4)
Chemical Name	N-[2-[4-cyano-2-fluoro-N-[(3-methylimidazol-4-yl)methyl]anilino]ethyl]-N-(cyclohexylmethyl)pyridine-2-sulfonamide;methanesulfonic acid
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 Note: Please store this product in a sealed and protected environment, avoid exposure to moisture.
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

Targets	IC50: 250 nM (FT) and 520 nM (GGT)[1]
ln Vitro	Human cancer cells that are KRAS-dependent but not mutant KRAS-dependent undergo apoptosis when exposed to FGTI-2734 mesylate (1-30 μM; 72 hours) [1]. The inhibition of HDJ2, RAP1A, KRAS, NRAS, and protein prenylation is achieved by FGTI-2734 mesylate (3-30 μM; 72 hours). In RAS-transformed mouse NIH3T3 cells as well as mutated KRAS human cancer cells, FGTI-2734 mesylate inhibits KRAS membrane localization [1].
ln Vivo	Mesylate FGTI-2734 (ip; 100 mg/kg/day for 18 to 25 days) only inhibits the growth of tumors that are dependent on KRAS; it has no effect on tumors that are independent of KRAS[1].
Cell Assay	Apoptosis Analysis[1] Cell Types: MiaPaCa2, L3.6pl, Calu6 cells Tested Tested Concentrations: 1, 3, 10, 30 μM Incubation Duration: 72 hrs (hours) Experimental Results: Induced apoptosis in mutant KRAS-dependent human cancer cell lines Western Blot Analysis[1] Cell Types: KRAS, HRAS, and NRAS-transformed NIH3T3 cells Tested Tested Concentrations: 3, 10, 30 μM Incubation Duration: 72 hrs (hours) Experimental Results: Inhibited both protein prenylation of HDJ2, RAP1A, KRAS and NRAS.
Animal Protocol	Animal/Disease Models: Male SCID-bg mice following injection of MiaPaCa2, L3.6pl, Calu6, A549, H460 and DLD1 cancer cells[1] Doses: 100 mg/kg Route of Administration: Intraperitoneally; daily; for 18 to 25 days Experimental Results: Inhibited tumor growth in mutant KRAS-dependent tumors.
References	[1]. Dual farnesyl and geranylgeranyl transferase inhibitor thwarts mutant KRAS-driven patient-derived pancreatic tumors. Clin Cancer Res. 2019 Jun 21.

Solubility Data

Solubility (In Vitro)

DMSO: 75 mg/mL (123.61 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 3 mg/mL (4.94 mM) (saturation unknown) in 10% DMSO + 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 30.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL 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: ≥ 3 mg/mL (4.94 mM) (saturation unknown) in 10% DMSO + 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 30.0 mg/mL clear DMSO 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: ≥ 3 mg/mL (4.94 mM) (saturation unknown) in 10% DMSO + 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 30.0 mg/mL clear DMSO 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	1.6482 mL	8.2409 mL	16.4818 mL
	5 mM	0.3296 mL	1.6482 mL	3.2964 mL
	10 mM	0.1648 mL	0.8241 mL	1.6482 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.