P2Y Antagonist II, BPTU

A phenoxypyridinyl-phenylurea that acts as a highly selective P2Y₁ antagonist (K_i = 6 nM against 0.5 nM [β-³³P]-2-MeS-ADP in competitive binding assays toward human P2Y₁), while displaying much reduced or no affinity toward other P2Y family G-protein-coupled purinergic receptors (K_i = ≥2.5 µM against 0.5 nM [β-³³P]-2-MeS-ADP binding toward hP2Y₁₄; K_i >15 µM toward human P2Y₂, P2Y₆, P2Y₁₁, and P2Y₁₂). Effectively inhibits 2.5 µM ADP-induced platelet aggregation in vitro (IC₅₀ = 2.1 µM using human platelet rich plasma) and reduces FeCl₂-induced (via 10 min localized artery surface exposure to 50% FeCl₂) carotid artery internal thrombus (blood clot) formation in anesthetized rats in vivo (by 68% 50 min post 10 min FeCl₂ exposure; single 10 mg/kg i.v. 15 min prior to FeCl₂ exposure, followed by continuous i.v. infusion at 10 mg/kg/h) with only 3.3- and 3.1-fold enhanced cuticle and mesenteric bleeding time, respectively. The same antithrombosis efficacy when achieved with the P2Y₁₂ antagonist Clopidogrel (20 mg/kg p.o.) is reported to result in much prolonged cuticle and mesenteric bleeding time (4.1- and 8.2-fold of control level, respectively). Pharmacokinetic studies in rats indicate a moderate oral bioavailability (F = 10%; C_max = 5.83 µM; T_max = 2 h; T_1/2 = 1.43 h; 30 mg/kg delivered with 10% cremophor:10% EtOH:80% H₂O).

Primary Target
P2Y₁

Reversible: yes

Packaged under inert gas

Following reconstitution, aliquot and freeze (-20°C). Stock solutions are stable for up to 6 months at -20°C.

Zhang, D., et al. 2015. Nature In press.
Chao, H., et al. 2013. J. Med. Chem.56, 1704.

CALBIOCHEM is a registered trademark of Merck KGaA, Darmstadt, Germany

Toxicity: Standard Handling (A)