The target of Prasugrel [2]

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.

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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]

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].

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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]

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]

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]

0.03-3 mg/kg/day; p.o.
Mice and rats

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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]

Absorption: Prasugrel is rapidly absorbed after oral administration, with high bioavailability and a peak time (tmax) of approximately 1-2 hours [2]. Metabolism: Prasugrel is a prodrug, mainly metabolized in the liver by the cytochrome P450 enzyme system, rapidly generating the active metabolite R-138727. Its metabolic conversion efficiency is significantly higher than that of clopidogrel [2]. Distribution: The active metabolite is widely distributed throughout the body [2]. Excretion: The drug metabolite is mainly excreted via the kidneys, with a half-life (t1/2) of approximately 7-10 hours [2].

The main toxicity-related risk of prasugrel is bleeding tendency. In in vivo studies, a slight increase in bleeding risk was observed in the high-dose group, but no significant hepatotoxicity or nephrotoxicity was found [2]. There is currently no clear median lethal dose (LD50) data. Compared with clopidogrel, prasugrel did not significantly increase the bleeding risk under similar antiplatelet effects [2].

[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.

Epothilone B is an epothilone derivative of epothilone D, in which the double bonds on its macrocycle are oxidized to the corresponding epoxide (S,S stereoisomer). It exhibits apoptosis-inducing, antitumor, and microtubule-stabilizing effects. It is both an epothilone and an epoxide. Epothilone B is a 16-membered macrocyclic lactone with biological effects similar to paclitaxel. Epothilone B has been reported to exist in the myxobacteria Sorangium cellulosum and Apis cerana, and relevant data exist. Patupilone is a compound isolated from the myxobacteria Sorangium cellulosum. Similar to paclitaxel, patchilone induces microtubule polymerization and stabilizes microtubules, protecting them from depolymerization. In addition to promoting tubulin polymerization and stabilizing microtubules, this drug is cytotoxic to cells overexpressing P-glycoprotein, a property that distinguishes it from taxanes. Patupilone may cause complete cell cycle arrest. Drug Indications Studied for the treatment of ovarian cancer, lung cancer, brain cancer, breast cancer, and gastric cancer. Other and unspecified malignancies of reproductive organs – fallopian tubes (ovarian tubes, uterine tubes), retroperitoneal and peritoneal malignancies – unspecified peritoneum. Mechanism of Action The primary mechanism of action of epothilones is the inhibition of microtubule function. Microtubules are crucial for cell division, therefore epothilones prevent normal cell division. Epothilone B exhibits the same biological effects as paclitaxel in vitro and in cultured cells. This is because they have the same binding site and affinity for microtubules. Similar to paclitaxel, epothilone B binds to the αβ-tubulin heterodimer subunit. Once bound, the dissociation rate of αβ-tubulin decreases, thereby stabilizing microtubules. Furthermore, epothilone B has been shown to induce microtubule polymerization in the absence of GTP to form microtubules. This is due to the formation of microtubule bundles throughout the cytoplasm. Finally, epothilone B also causes cell cycle arrest in the G2/M phase, leading to cytotoxicity and ultimately inducing apoptosis. Prasugrel is an antiplatelet drug belonging to the ADP receptor antagonist class. It prevents thrombosis by irreversibly binding to the platelet P2Y12 receptor, inhibiting ADP-mediated platelet activation and aggregation [1][2]. Its mechanism of action is similar to clopidogrel, but due to its higher efficiency in generating active metabolites, it has a stronger and faster-acting antiplatelet effect in vivo [2]. Clinically, it is used to treat thrombotic diseases such as acute coronary syndrome, aiming to reduce the risk of cardiovascular events [1].

C20H20FNO3S

373.44

373.115

150322-43-3

389574-19-0； 389574-20-3

448013

White to light yellow solid powder

1.347

493.5ºC at 760 mmHg

122 °C

252.3ºC

0mmHg at 25°C

1.619

3.828

2

8

2

35

816

7

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

DTGLZDAWLRGWQN-UHFFFAOYSA-N

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

5-(2-cyclopropyl-1-(2-fluorophenyl)-2-oxoethyl)-4,5,6,7-tetrahydrothieno[3,2-c]pyridin-2-yl acetate

CS-747; LY-640315; PCR-4099; CS747; LY640315; PCR4099; CS 747; LY 640315; PCR 4099; trade name Effient; Prasita

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

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.

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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.

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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.

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 (Please use freshly prepared in vivo formulations for optimal results.)