Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.21.6 (thromboplastin)
 13,278 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Thrombin and factor Xa (fXa) are the only serine proteases for which small, potent, selective, noncovalent inhibitors have been developed, which are ultimately intended as drug development candidates (in this case as anticoagulants). Noncovalent inhibitors may be more selective and chemically and metabolically less reactive than covalent inhibitors. In addition, noncovalent inhibitors are more likely to have fast-binding kinetics which is particularly important in the development of thrombin inhibitors. TAME derived noncovalent thrombin inhibitors argatroban, napsagatran, and UK 156,406 have entered clinical trials as anticoagulants, the latter as an orally active agent. Serine trap deletion from substrate-like peptides led to the development of inogatran and melagatran, both of which have entered clinical trials as intravenous agents. The use of 3-aminopyridinone and pyrazinone acetamide peptidomimetic templates has resulted in the development of L-375,378 which has been chosen for clinical development as an orally active anticoagulant. Recently, compounds which do not have the conventional hydrogen bonding capabilities of peptides have begun to appear in the thrombin literature. Publications on noncovalent fXa inhibitors cover this type of peptidomimetic almost exclusively.
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PMID:Small, noncovalent serine protease inhibitors. 1018 77

Chondroitin sulfates proteoglycans were isolated from human placenta. For the identification of enzymatic digestion products of isolated proteoglycan, strong anion, exchange-high performance liquid chromatography (SAX-HPLC) was performed. By the action of chondroitin ABC and chondroitin B lyase, three unsaturated disaccharides 2-acetamide-2-deoxy-3-O-(beta-D-gluco-4-enepyranosyluronic acid)-D-galactose (deltaDi-OS), 2-acetamide-2-deoxy-3-O-(beta-D-gluco-4-enepyranosyluronic acid)-6-O-sulfo-D-galactose (deltaDi-6S) and 2-acetamide-2-deoxy-3-O-(beta-D-gluco-4-enepyranosyluronic acid)-4-O-sulfo-D-galactose (deltaDi-4S) were produced from the human placenta proteoglycan. The anticoagulant activity of chondroitin sulfate proteoglycan was evaluated by activated partial thromboplastin time (aPTT) assay and thrombin time (TT) assay. The clotting times of aPTT and TT were increased from 72 to 144 sec and 19 to 27 sec, respectively. The immuno-modulating activity of chondroitin sulfate proteoglycan was examined by cell proliferation assay and these results suggest that it may play a role in suppression of the function of immune-related cells.
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PMID:Isolation and characterization of proteoglycan derived from human placenta and its biological activities. 1083 48

N-[3-[[[(1S)-4-(5-Amino-2-pyridinyl)-1-[[4-difluoromethylene)-1-piperidinyl]carbonyl]butyl]amino]sulfonyl][1,1'-biphenyl]-2-yl]acetamide hydrochloride (SSR182289A) is a novel, potent, and selective thrombin inhibitor. We have examined the antithrombotic properties of SSR182289A administered by i.v. and p.o. routes in several different animal thrombosis models in comparison with reference antithrombotic agents. Oral administration of SSR182289A produced dose-related antithrombotic effects in the following models; rat venous thrombosis (ED(50) 0.9 mg/kg p.o.), rat silk thread arterio-venous (AV) shunt (ED(50) 3.8 mg/kg p.o.), rat thromboplastin-induced AV shunt (ED(50) 3.1 mg/kg p.o.), rat carotid artery thrombosis (ED(200) 5.9 mg/kg p.o.), and rabbit venous thrombosis (ED(50) 7.5 mg/kg p.o.). Administered as an i.v. bolus, SSR182289A showed antithrombotic activity in the above models with ED(50)/ED(200) values in the range of 0.2 to 1.9 mg/kg i.v. SSR182289A increased rat tail transection bleeding time at doses > or =10 mg/kg p.o. In the rat thromboplastin-induced AV shunt model, SSR182289A 10 mg/kg p.o. produced marked antithrombotic effects at 30, 60, 120, and 240 min after administration. Hence, SSR182289A demonstrates potent oral antithrombotic properties in animal venous, AV-shunt, and arterial thrombosis models.
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PMID:Antithrombotic properties of SSR182289A, a new, orally active thrombin inhibitor. 1253 8