OSI754 (also known as CP-609754, CP-609,754, LNK-754) is a novel and potent farnesyltransferase inhibitor (TFI) that has potential anticancer activity. Since farnesyltransferase is known to prevent proper functioning of Ras, a family of proteins often abnormally activated in cancer, FTIs were first developed as potential anticancer agents. A number of FTIs underwent preclinical testing but were found to have major side effects, while others entered clinical development in a variety of cancers, only to be discontinued at phase I due to a lack of efficacy.

Physicochemical Properties

Molecular Formula	C29H22CLN3O2
Molecular Weight	479.96
Exact Mass	479.14
CAS #	1190094-64-4
Related CAS #	(Rac)-CP-609754;439153-64-7
PubChem CID	46208720
Appearance	Off-white to yellow solid powder
Density	1.23±0.1 g/cm3
Boiling Point	702.4±60.0 °C
LogP	4.857
Hydrogen Bond Donor Count	1
Hydrogen Bond Acceptor Count	3
Rotatable Bond Count	5
Heavy Atom Count	35
Complexity	874
Defined Atom Stereocenter Count	1
SMILES	CN1C=NC=C1[C@@](C2=CC=C(C=C2)Cl)(C3=CC4=C(C=C3)N(C(=O)C=C4C5=CC=CC(=C5)C#C)C)O
InChi Key	JAHDAIPFBPPQHQ-GDLZYMKVSA-N
InChi Code	InChI=1S/C29H22ClN3O2/c1-4-19-6-5-7-20(14-19)24-16-28(34)33(3)26-13-10-22(15-25(24)26)29(35,27-17-31-18-32(27)2)21-8-11-23(30)12-9-21/h1,5-18,35H,2-3H3/t29-/m1/s1
Chemical Name	(R)-6-((4-chlorophenyl)(hydroxy)(1-methyl-1H-imidazol-5-yl)methyl)-4-(3-ethynylphenyl)-1-methylquinolin-2(1H)-one
Synonyms	CP-609754; CP609754; CP 609754; LNK 754; LNK754; LNK-754; OSI 754; OSI754; OSI-754
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	Reversible farnesyl growth enzyme kinase with a slow on/off rate is CP-609754 (CP-609,754). The analysis of compounds tagged with [35S]methionine using SDS-PAGE [1] indicates that CP-609754 is competitive for the isoprene receptor (H-Ras protein), but not for the isoprene donor farnesyl PPI. When it comes to binding to Ras protein, CP-609754 reacts to and competes with the farnesyltransferase-farnesylPPI complex. In 3T3 transfectants, CP-609754 specifically prevents the farnesylation of H- and K-Ras proteins [1].
ln Vivo	In vivo activity of CP-609754 (CP-609,754) against 3T3 H-ras (61L) cancers has been reported [1]. Tumor suppression was achieved by continuous intraperitoneal infusion of CP-609754; tumor growth inhibition was >50%, tumor farnesyl transcriptase activity was inhibited >30%, and CP-609754 tumor growth concentration remains above 118 ng/mL. Tumor regression reached a dose of 100 mg/kg when CP-609754 was applied twice a day to the side wall [1].
References	[1]. A phase I open label study of the farnesyltransferase inhibitor CP-609,754 in patients with advanced malignant tumors. Clin Cancer Res. 2004 Nov 1;10(21):7127-35.
Additional Infomation	LNK 754 has been investigated in Mild Alzheimer's Disease. CP-609,754 is a quinolinone derivative that inhibits farnesyl protein transferase, an enzyme that mediates the farnesylation of RAS, causing possible inhibition of the RAS pathway.

Solubility Data

Solubility (In Vitro)

DMSO:≥ 10 mM Water:N/A Ethanol:N/A

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 2.5 mg/mL (5.21 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 25.0 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: ≥ 2.5 mg/mL (5.21 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 25.0 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	2.0835 mL	10.4175 mL	20.8351 mL
	5 mM	0.4167 mL	2.0835 mL	4.1670 mL
	10 mM	0.2084 mL	1.0418 mL	2.0835 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.