L-778123 dihydrochloride is a dual inhibitor of FPTase and GGPTase-I, with IC50 values of 2 nM and 98 nM respectively.

Physicochemical Properties

Molecular Formula	C22H22CL3N5O
Molecular Weight	478.80
Exact Mass	477.088
CAS #	183499-56-1
PubChem CID	22464354
Appearance	Typically exists as solid at room temperature
Hydrogen Bond Donor Count	2
Hydrogen Bond Acceptor Count	4
Rotatable Bond Count	5
Heavy Atom Count	31
Complexity	614
Defined Atom Stereocenter Count	0
InChi Key	XNGJWEBJQJQXQR-UHFFFAOYSA-N
InChi Code	InChI=1S/C22H20ClN5O.2ClH/c23-19-2-1-3-20(10-19)28-9-8-26(15-22(28)29)14-21-12-25-16-27(21)13-18-6-4-17(11-24)5-7-18;;/h1-7,10,12,16H,8-9,13-15H2;2*1H
Chemical Name	4-[[5-[[4-(3-chlorophenyl)-3-oxopiperazin-1-yl]methyl]imidazol-1-yl]methyl]benzonitrile;dihydrochloride
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	L-778123 dihydrochloride alone has no significant cytotoxicity against HT-29 and A549 cell lines (IC50: >100 μM), but it can synergize with Doxorubicin (HY-15142A) with IC50s reduced to 1.72 and 1.52 μM, respectively[2]. L-778123 dihydrochloride inhibits the proliferation of myeloid leukemia cell lines with IC50 values of 0.2 μM-1.8 μM and IC50 values of 0.1 μM-161.8 μM in primary samples[3]. L-778123 dihydrochloride (0-1 μM, 12 hours; or 5 μM, 6 hours) inhibits H-RAS prenylation in HL-60 cells and suppresses phosphorylated MEK-1/2 levels (5 μM, 24 hours)[3]. L-778123 dihydrochloride (0-100 μM, 72 hours) inhibits lymphocyte activation (markers: CD71 or CD25) and function in human PBMCs [4].
ln Vivo	L-778123 dihydrochloride (50 mg/kg/day, infusion, 7 days) inhibits HDJ2 and Rap1A prenylation, but not Ki-Ras prenylation, in dog PBMC cells [1].
References	[1]. Preclinical and clinical pharmacodynamic assessment of L-778,123, a dual inhibitor of farnesyl:protein transferase and geranylgeranyl:protein transferase type-I. Mol Cancer Ther. 2002 Jul;1(9):747-758. [2]. Comparison of Cytotoxic Activity of L778123 as a Farnesyltranferase Inhibitor and Doxorubicin against A549 and HT-29 Cell Lines. Adv Pharm Bull. 2013;3(1):73-77. [3]. The Farnesyltransferase Inhibitor (FTI) L-778,123 Displays Promising Anti-Leukemia Activity. Blood (2008); 112 (11): 2627. [4]. Inhibition of lymphocyte activation and function by the prenylation inhibitor L-778,123. Invest New Drugs. 2005 Jan;23(1):21-9.

Solubility Data

Solubility (In Vitro)

May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples

Solubility (In Vivo)

Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples. Injection Formulations (e.g. IP/IV/IM/SC) Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] *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. Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline) Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline) Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline) Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil) Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Oral Formulations Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). Oral Formulation 3: Dissolved in PEG400 Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose Oral Formulation 6: Mixing with food powders Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	2.0886 mL	10.4428 mL	20.8855 mL
	5 mM	0.4177 mL	2.0886 mL	4.1771 mL
	10 mM	0.2089 mL	1.0443 mL	2.0886 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.