Rilapladib (formerly aslo known as SB-659032 and GTPL-7376) is a novel, potent and selective lipoprotein-associated phospholipase A2 (Lp-PLA2) inhibitor with an IC50 of 230 pM, also a PAFR (Platelet Activating Factor Receptor) antagonist.

Physicochemical Properties

Molecular Formula	C40H38N3O3F5S
Molecular Weight	735.80502
Exact Mass	735.255
CAS #	412950-08-4
PubChem CID	9918381
Appearance	Light yellow to yellow solid powder
Density	1.36g/cm3
LogP	8.335
Hydrogen Bond Donor Count	0
Hydrogen Bond Acceptor Count	11
Rotatable Bond Count	12
Heavy Atom Count	52
Complexity	1200
Defined Atom Stereocenter Count	0
InChi Key	NNBGCSGCRSCFEA-UHFFFAOYSA-N
InChi Code	InChI=1S/C40H38F5N3O3S/c1-51-22-21-46-19-17-32(18-20-46)47(24-27-9-11-28(12-10-27)29-13-15-31(16-14-29)40(43,44)45)37(50)25-48-35-8-3-2-6-33(35)36(49)23-38(48)52-26-30-5-4-7-34(41)39(30)42/h2-16,23,32H,17-22,24-26H2,1H3
Chemical Name	2-[2-[(2,3-difluorophenyl)methylsulfanyl]-4-oxoquinolin-1-yl]-N-[1-(2-methoxyethyl)piperidin-4-yl]-N-[[4-[4-(trifluoromethyl)phenyl]phenyl]methyl]acetamide
Synonyms	SB-659032; GTPL 7376; D05728; SB659032; GTPL-7376; D-05728; SB 659032; GTPL7376;
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	By lowering PAF levels and biological activity (as PAF kinase), rilapadib can decrease the manufacture of Lp-PLA2 and avert potential negative effects from Lp-PLA2. [2]
References	[1]. Platelet aggregation unchanged by lipoprotein-associated phospholipase A₂ inhibition: results from an in vitro study and two randomized phase I trials. PLoS One. 2014 Jan 27;9(1):e83094. [2]. Computational Investigation of Darapladib and Rilapladib Binding to Platelet Activating Factor Receptor. A Possible Mechanism of Their Involvement in Atherosclerosis. International Journal of Chemistry; Vol. 6, No. 1; 2014.
Additional Infomation	Rilapladib is the third genomics-derived small molecule drug arising from the Human Genome Sciences-GlaxoSmithKline collaboration to enter clinical development. It is a lipoprotein-associated phospholipase A2 (Lp-PLA2) inhibitor. Lp-PLA2 is an enzyme associated with the formation of atherosclerotic plaques. Drug Indication Investigated for use/treatment in atherosclerosis and cardiovascular disorders. Mechanism of Action Rilapladib is a Lp-PLA2 inhibitor. Lp-PLA2 has been found to be enriched in the highly atherogenic lipoprotein subfraction of small dense LDL, which is susceptible to oxidative modification. Moreover, enzyme levels are increased in patients with hyperlipidaemia, stroke, Type 1 and Type 2 diabetes mellitus, as well as in post-menopausal women. As such, plasma Lp-PLA2 levels tend to be elevated in those individuals who are considered to be at risk of developing accelerated atherosclerosis and clinical cardiovascular events. Thus, inhibition of the Lp-PLA2 enzyme would be expected to stop the build up of this fatty streak (by inhibition of the formation of lysophosphatidylcholine), and so be useful in the treatment of atherosclerosis.

Solubility Data

Solubility (In Vitro)

DMSO : ~86.67 mg/mL (~117.79 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 2.25 mg/mL (3.06 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 22.5 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: 2.25 mg/mL (3.06 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 22.5 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: ≥ 2.25 mg/mL (3.06 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 22.5 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	1.3590 mL	6.7952 mL	13.5905 mL
	5 mM	0.2718 mL	1.3590 mL	2.7181 mL
	10 mM	0.1359 mL	0.6795 mL	1.3590 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.