Prasugrel (formerly CS-747, PCR-4099; LY-640315; trade name Effient; Prasita), a piperazine derivative, is an irreversible and thienopyridine-based ADP receptor (P2Y12) antagonist approved as an antiplatelet and anticoagulant drug used for the reduction of thrombotic cardiovascular events. As a platelet aggregation inhibitor, it is used to prevent thrombosis in patients with acute coronary syndrome; unstable angina and myocardial infarction, as well as in those undergoing percutaneous coronary interventions. Prasugrel was also approved for use in Europe in February 2009 and On July 10, 2009 in the US for for the reduction of thrombotic cardiovascular events in patients with acute coronary syndrome who are to be managed with PCI.

Physicochemical Properties

Molecular Formula	C20H20FNO3S
Molecular Weight	373.44
Exact Mass	373.115
CAS #	150322-43-3
Related CAS #	389574-19-0； 389574-20-3
PubChem CID	448013
Appearance	White to light yellow solid powder
Density	1.347
Boiling Point	493.5ºC at 760 mmHg
Melting Point	122 °C
Flash Point	252.3ºC
Vapour Pressure	0mmHg at 25°C
Index of Refraction	1.619
LogP	3.828
Hydrogen Bond Donor Count	2
Hydrogen Bond Acceptor Count	8
Rotatable Bond Count	2
Heavy Atom Count	35
Complexity	816
Defined Atom Stereocenter Count	7
SMILES	C[C@H]1CCC[C@@]2([C@@H](O2)C[C@H](OC(=O)C[C@@H](C(C(=O)[C@@H]([C@H]1O)C)(C)C)O)/C(=C/C3=CSC(=N3)C)/C)C
InChi Key	DTGLZDAWLRGWQN-UHFFFAOYSA-N
InChi Code	InChI=1S/C20H20FNO3S/c1-12(23)25-18-10-14-11-22(9-8-17(14)26-18)19(20(24)13-6-7-13)15-4-2-3-5-16(15)21/h2-5,10,13,19H,6-9,11H2,1H3
Chemical Name	5-(2-cyclopropyl-1-(2-fluorophenyl)-2-oxoethyl)-4,5,6,7-tetrahydrothieno[3,2-c]pyridin-2-yl acetate
Synonyms	CS-747; LY-640315; PCR-4099; CS747; LY640315; PCR4099; CS 747; LY 640315; PCR 4099; trade name Effient; Prasita
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	The target of Prasugrel [2]
ln Vitro	In vitro activity: Prasugrel is a novel orally active thienopyridine with faster, higher and more reliable inhibition of platelet aggregation than clopidogrel reflecting its metabolism in vivo to an active metabolite with selective P2Y(12) antagonistic activity. In vitro experiments showed that Prasugrel requires metabolic activation to generate its active metabolite (R-138727), which inhibits ADP-induced platelet aggregation. The antiplatelet activity of this active metabolite is similar to that of clopidogrel's active metabolite (R-130964) [2] - Incubation experiments with human liver microsomes demonstrated that the conversion efficiency of Prasugrel to its active metabolite is significantly higher than that of clopidogrel [2]
ln Vivo	With an IC50 value of 1.8 μM, the active metabolite of prasugrel inhibits the platelet aggregation generated by adenosine ADP (10 μM) in vitro in rat platelets [2]. In comparison to clopidogrel, prasugrel operates more quickly and effectively in the body. The body must undergo metabolic processing on the inactive prodrug prasugrel in order to create the active antiplatelet metabolite. The intestines absorb prasugrel very quickly. The active metabolite's plasma concentration increases to a maximum in 1 hour, becomes effective in 1-2 hours, and maximally inhibits platelet aggregation following oral administration of a conventional loading dose of 60 mg [1]. In canine in vivo experiments, oral administration of Prasugrel (0.3, 1, 3 mg/kg) dose-dependently inhibited ADP-induced platelet aggregation. At the 3 mg/kg dose, the maximum aggregation inhibition rate reached over 80%, and the inhibitory effect lasted more than 24 hours [2] - In rat in vivo experiments, Prasugrel was rapidly absorbed and metabolized to the active metabolite after oral administration. The plasma concentration peak of its active metabolite was higher than that of clopidogrel's active metabolite, with a shorter time to peak (tmax) [2] - Comparative experiments indicated that at the same oral dose, the in vivo antiplatelet aggregation effect of Prasugrel was significantly stronger than that of clopidogrel [2]
Enzyme Assay	Platelet aggregation inhibition assay: Platelet-rich plasma (PRP) was isolated from animal or human blood. Prasugrel or its active metabolite at different concentrations was added to PRP and incubated for a certain period. ADP was then added as an inducer, and platelet aggregation rate was detected by a platelet aggregometer to calculate the inhibitory effect [2] - Hepatic metabolic conversion assay: Prasugrel was co-incubated with liver microsomes and coenzyme systems. The production of the active metabolite was separated and quantitatively detected by high-performance liquid chromatography (HPLC), and the metabolic conversion efficiency was compared with that of clopidogrel [2]
Cell Assay	Platelet isolation and aggregation assay: Venous blood was collected from animals or humans, and PRP was obtained by centrifugation. After adjusting the platelet concentration, Prasugrel was added for pretreatment, followed by ADP-induced aggregation. The platelet aggregation curve was recorded continuously, and the aggregation rate was used as the evaluation index [2]
Animal Protocol	0.03-3 mg/kg/day; p.o. Mice and rats Canine antiplatelet activity experiment: Healthy dogs were selected and randomly divided into groups. They were orally administered Prasugrel or clopidogrel at doses of 0.3, 1, or 3 mg/kg. Venous blood was collected before administration and at different time points after administration. PRP was isolated to detect ADP-induced platelet aggregation rate, so as to evaluate the drug potency and duration [2] - Rat pharmacokinetic experiment: After oral or intravenous administration of Prasugrel to rats, blood samples were collected at different time points. The concentrations of the parent drug and active metabolite in plasma were detected by liquid chromatography-tandem mass spectrometry (LC-MS/MS) to analyze the pharmacokinetic parameters [2]
ADME/Pharmacokinetics	Absorption: Prasugrel is rapidly absorbed after oral administration with high bioavailability, and the time to peak (tmax) is approximately 1-2 hours [2] - Metabolism: Prasugrel is a prodrug, mainly metabolized by the cytochrome P450 enzyme system in the liver to rapidly form the active metabolite R-138727. Its metabolic conversion efficiency is significantly higher than that of clopidogrel [2] - Distribution: The active metabolite is widely distributed in tissues throughout the body [2] - Excretion: The drug metabolites are mainly excreted through the kidneys, with a half-life (t1/2) of approximately 7-10 hours [2]
Toxicity/Toxicokinetics	The main toxicity-related risk of Prasugrel is bleeding tendency. Slight increase in bleeding was observed in the high-dose group in in vivo experiments, but no obvious hepatotoxicity or nephrotoxicity was found [2] - No definite median lethal dose (LD50) data is reported. Compared with clopidogrel, Prasugrel does not significantly increase the bleeding risk at similar antiplatelet effects [2]
References	[1]. Anti-platelet therapy: ADP receptor antagonists. Br J Clin Pharmacol. 2011 Oct;72(4):647-57. [2]. The greater in vivo antiplatelet effects of prasugrel as compared to clopidogrel reflect more efficient generation of its active metabolite with similar antiplatelet activity to that of clopidogrel's active metabolite. J Thromb Haemost. 2007 Jul;5(7):1545-51.
Additional Infomation	Epothilone B is an epithilone that is epithilone D in which the double bond in the macrocyclic ring has been oxidised to the corresponding epoxide (the S,S stereoisomer). It has a role as an apoptosis inducer, an antineoplastic agent and a microtubule-stabilising agent. It is an epothilone and an epoxide. Epothilone B is a 16-membered macrolide that mimics the biological effects of taxol. Epothilone B has been reported in Sorangium cellulosum and Apis cerana with data available. Patupilone is a compound isolated from the myxobacterium Sorangium cellulosum. Similar to paclitaxel, patupilone induces microtubule polymerization and stabilizes microtubules against depolymerization conditions. In addition to promoting tubulin polymerization and stabilization of microtubules, this agent is cytotoxic for cells overexpressing P-glycoprotein, a characteristic that distinguishes it from the taxanes. Patupilone may cause complete cell-cycle arrest. Drug Indication Investigated for use/treatment in ovarian cancer, lung cancer, brain cancer, breast cancer, and gastric cancer. Malignant neoplasm of other and unspecified genital organs - Fallopian tube (oviduct, uterine tube), Malignant neoplasm of the retroperitoneum and peritoneum - Peritoneum, unspecified Mechanism of Action The principal mechanism of the epothilone class is inhibition of microtubule function. Microtubules are essential to cell division, and epothilones therefore stop cells from properly dividing. Epothilone B possess the same biological effects as taxol both in vitro and in cultured cells. This is because they share the same binding site, as well as binding affinity to the microtubule. Like taxol, epothilone B binds to the αβ-tubulin heterodimer subunit. Once bound, the rate of αβ-tubulin dissociation decreases, thus stabilizing the microtubules. Furthermore, epothilone B has also been shown to induce tubulin polymerization into microtubules without the presence of GTP. This is caused by formation of microtubule bundles throughout the cytoplasm. Finally, epothilone B also causes cell cycle arrest at the G2-M transition phase, thus leading to cytotoxicity and eventually cell apoptosis. Prasugrel is an antiplatelet drug belonging to the ADP receptor antagonist class. It inhibits ADP-mediated platelet activation and aggregation by irreversibly binding to the platelet P2Y12 receptor, thereby preventing thrombosis [1][2] - Its mechanism of action is similar to that of clopidogrel, but due to the higher efficiency of active metabolite formation, it has stronger and faster-onset antiplatelet effects in vivo [2] - It is clinically indicated for the treatment of thrombotic diseases such as acute coronary syndrome, aiming to reduce the risk of cardiovascular events [1]

Solubility Data

Solubility (In Vitro)

DMSO: 30 mg/mL (80.3 mM) Water:<1 mg/mL Ethanol:<1 mg/mL

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 2.5 mg/mL (6.69 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 (6.69 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 25.0 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: ≥ 2.5 mg/mL (6.69 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	2.6778 mL	13.3890 mL	26.7781 mL
	5 mM	0.5356 mL	2.6778 mL	5.3556 mL
	10 mM	0.2678 mL	1.3389 mL	2.6778 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.