Laropiprant (aslo known as MK-0524; Cordaptive) is a novel, potent, selective DP [prostaglandin D2 (PGD2) receptor (DP)] receptor antagonist with Ki values of 0.57 nM and 2.95 nM for DP receptor and TP Receptor, respectively. Laropiprant, which was formerly prescribed in conjunction with niacin to lower blood cholesterol (LDL and VLDL), is no longer in production because of an increase in adverse effects that outweigh any cardiovascular benefits. The U.S. Food and Drug Administration (FDA) sent a "not approved" letter for Cordaptive on April 28, 2008. On July 3, 2008, the European Medicines Agency (EMA) approved Tredaptive. On January 11, 2013, Merck & Co. Inc. declared that they were discontinuing the medication globally due to suggestions from European regulators.

Physicochemical Properties

Molecular Formula	C21H19CLFNO4S
Molecular Weight	435.89600
Exact Mass	435.07
Elemental Analysis	C, 57.87; H, 4.39; Cl, 8.13; F, 4.36; N, 3.21; O, 14.68; S, 7.35
CAS #	571170-77-9
Related CAS #	Laropiprant sodium; 572874-50-1
PubChem CID	9867642
Appearance	White to off-white solid powder
Density	1.5±0.1 g/cm3
Boiling Point	710.0±60.0 °C at 760 mmHg
Melting Point	175∶ºC
Flash Point	383.2±32.9 °C
Vapour Pressure	0.0±2.4 mmHg at 25°C
Index of Refraction	1.664
LogP	3.82
Hydrogen Bond Donor Count	1
Hydrogen Bond Acceptor Count	5
Rotatable Bond Count	5
Heavy Atom Count	29
Complexity	721
Defined Atom Stereocenter Count	1
SMILES	O=S(C1=CC(F)=CC2=C1N(C3=C2CC[C@@H]3CC(O)=O)CC4=CC=C(Cl)C=C4)(C)=O
InChi Key	NXFFJDQHYLNEJK-CYBMUJFWSA-N
InChi Code	InChI=1S/C21H19ClFNO4S/c1-29(27,28)18-10-15(23)9-17-16-7-4-13(8-19(25)26)20(16)24(21(17)18)11-12-2-5-14(22)6-3-12/h2-3,5-6,9-10,13H,4,7-8,11H2,1H3,(H,25,26)/t13-/m1/s1
Chemical Name	2-[(3R)-4-[(4-chlorophenyl)methyl]-7-fluoro-5-methylsulfonyl-2,3-dihydro-1H-cyclopenta[b]indol-3-yl]acetic acid
Synonyms	MK-0524; Laropiprant; MK0524; MK 0524; Trade name: Cordaptive; Tredaptive
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

Targets	DP ( Ki = 0.57 nM ); TP Receptor ( Ki = 2.95 nM )
ln Vitro	Laropiprant is a potent, selective antagonist of the DP receptor with Ki values for the TP Receptor and DP receptor of 2.95 nM and 0.57 nM, respectively.[1]. Although laropiprant (1 µM) significantly inhibits the aggregation, it still negates the strong inhibition brought on by BW245c (3 nM) and PGD2 (30 nM). Laropiprant inhibits P-selectin expression, GPIIb/IIIa activation, and in vitro thrombus formation in addition to the DP receptor-dependent increase in VASP phosphorylation. By activating the TP and EP3 receptors, laropiprant counteracts the increased platelet aggregation. Niacin and laropiprant (10 µM) both prevent thrombus formation in vitro[2].
ln Vivo	Laropiprant (100-100 mg/kg; intravenous and oral; male) Sprague-Dawley rats) show positive pharmacokinetic characteristics. [3]. An analysis of pharmacokinetics in male Sprague-Dawley rats [3] The dosage by route (mg/kg) AUC0-∞ (μM·hr) Clp (mL/min/kg) Vdss (L/kg) T1/2 (hour) PO 5 96.0 2.1 0.9 7.6 PO 1 22.7 1.9 0.7 7.4 The dosage by route (mg/kg) AUC0-∞ (μM·hr) Cmax (micrometer) Tmax in hours F(%) IV 5 15.6 1.2 52.6 /
Cell Assay	Vena8Fluoro+ Biochips are coated with collagen (200 µg/mL) at 4°C for an entire night. After that, they are blocked for 30 minutes at room temperature using bovine serum albumin (10 µg/mL), and then they are cleaned. After being collected in sodium citrate, 1 µM of 3, 3-dihexyloxacarbocyanine iodide is incubated for 10 minutes in the dark with whole blood. Ten minutes prior to the onset of perfusion, PGD2 (30 nM), BW245c (3 nM), and the DP antagonist BWA868c or Laropiprant (1 µM) are added. In an additional series of tests, whole blood is exposed to 30 minutes of treatment with either niacin (3 mM), acetylsalicylic acid (1 mM), or laropiprant (1 µM and 10 µM). A final concentration of 1 mM of CaCl2 is added two minutes prior to the perfusion over the chip coated in collagen. The shear rate at which perfusion occurs is 30 dynes cm^2. The formation of thrombus is noted. DucoCell analysis software is used for computerized image analysis, where the area covered by the thrombus is computed. Percentage of the area covered in a control sample is used to express data[2].
References	[1]. Inverse agonist and pharmacochaperone properties of MK-0524 on the prostanoid DP1 receptor. PLoS One. 2013 Jun 10;8(6):e65767. [2]. Discovery of a potent and selective prostaglandin D2 receptor antagonist, [(3R)-4-(4-chloro-benzyl)-7-fluoro-5-(methylsulfonyl)-1,2,3,4-tetrahydrocyclopenta[b]indol-3-yl]-acetic acid (MK-0524). J Med Chem. 2007 Feb 22;50(4):794-806. [3]. The pharmacokinetics and disposition of MK-0524, a Prosglandin D2 Receptor 1 antagonist, in rats, dogs and monkeys. Xenobiotica. 2007 May;37(5):514-33.
Additional Infomation	Laropiprant is an indolyl carboxylic acid. Laropiprant is an ingredient in the EMA-withdrawn product Pelzont. Laropiprant is a prostaglandin D2 receptor (DP1) antagonist with niacin-induced vasodilation inhibiting activity. Laropiprant binds to and inhibits the activity of DP1, a G-protein coupled receptor. Via competing with prostaglandin D2 (PG D2) for binding to DP1, this agent prevents PG D2-induced vasodilation and increased blood flow. As niacin induces the synthesis of PG D2, predominantly in the skin, administration of laropiprant may prevent niacin-induced vasodilation in the skin and facial flushing.

Solubility Data

Solubility (In Vitro)

DMSO: ~87 mg/mL (199.6 mM) Ethanol: ~87 mg/mL

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 2.5 mg/mL (5.74 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 (5.74 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	2.2941 mL	11.4705 mL	22.9410 mL
	5 mM	0.4588 mL	2.2941 mL	4.5882 mL
	10 mM	0.2294 mL	1.1471 mL	2.2941 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.