GGTI-2154 HCl is a potent and specific inhibitor of geranylgeranyltransferase I (GGTase I) with IC50 of 21 nM. The selectivity of GGTI-2154 HCl for GGTase I is more than 200 times that of FTase (IC50=5600 nM). GGTI-2154 HCl may be utilized in cancer research.

Physicochemical Properties

Molecular Formula	C24H29CLN4O3
Molecular Weight	456.965064764023
Exact Mass	456.192
CAS #	478908-50-8
Related CAS #	GGTI-2154;251577-10-3
PubChem CID	69892739
Appearance	White to off-white solid powder
Hydrogen Bond Donor Count	5
Hydrogen Bond Acceptor Count	5
Rotatable Bond Count	9
Heavy Atom Count	32
Complexity	599
Defined Atom Stereocenter Count	1
SMILES	CC1=CC=CC=C1C2=C(C=CC(=C2)NCC3=CN=CN3)C(=O)N[C@@H](CC(C)C)C(=O)O.Cl
InChi Key	JQRKKNPKMYXQRS-FTBISJDPSA-N
InChi Code	InChI=1S/C24H28N4O3.ClH/c1-15(2)10-22(24(30)31)28-23(29)20-9-8-17(26-13-18-12-25-14-27-18)11-21(20)19-7-5-4-6-16(19)3;/h4-9,11-12,14-15,22,26H,10,13H2,1-3H3,(H,25,27)(H,28,29)(H,30,31);1H/t22-;/m0./s1
Chemical Name	(2S)-2-[[4-(1H-imidazol-5-ylmethylamino)-2-(2-methylphenyl)benzoyl]amino]-4-methylpentanoic acid;hydrochloride
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: 21 nM (GGTase I)[1]
ln Vitro	GGTI-2154 has an IC50 of 21 nM and prevents the transfer of geranylgeranyl from [3H]GGPP to H-Ras CVLL[1].
ln Vivo	In MMTV-v-Ha-Ras transgenic mice, GGTI-2154 (100 mg/kg/day; sc for 14 days) causes regression of breast tumors[2]. In nude mice, GGTI-2154 (50 mg/kg/day; ip for 50 days) suppresses the formation of A-549 tumors by 60%[1].
Animal Protocol	Animal/Disease Models: MMTV-v-Ha-ras transgenic mice bearing mammary carcinoma[2] Doses: 100 mg/kg/day Route of Administration: Sc with osmotic mini-pumps for 14 days Experimental Results: Halted the tumors aggressive growth. Resulted in rapid tumor regression within 3 days of initiation of drug treatment.
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 Oct 1;59(19):4919-26. [2]. 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)

DMSO : 250 mg/mL (547.08 mM) H2O : 4.76 mg/mL (10.42 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 25 mg/mL (54.71 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 250.0 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: ≥ 25 mg/mL (54.71 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 250.0 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: ≥ 25 mg/mL (54.71 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 250.0 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	2.1883 mL	10.9416 mL	21.8833 mL
	5 mM	0.4377 mL	2.1883 mL	4.3767 mL
	10 mM	0.2188 mL	1.0942 mL	2.1883 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.