コンテンツへスキップ
Merck

Nontoxic polyphosphate inhibitors reduce thrombosis while sparing hemostasis.

Blood (2014-09-10)
Richard J Travers, Rajesh A Shenoi, Manu Thomas Kalathottukaren, Jayachandran N Kizhakkedathu, James H Morrissey
要旨

Polyphosphate (polyP) is secreted by activated platelets and has been shown to contribute to thrombosis, suggesting that it could be a novel antithrombotic target. Previously reported polyP inhibitors based on polycationic substances, such as polyethylenimine, polyamidoamine dendrimers, and polymyxin B, although they attenuate thrombosis, all have significant toxicity in vivo, likely due to the presence of multiple primary amines responsible for their polyP binding ability. In this study, we examined a novel class of nontoxic polycationic compounds initially designed as universal heparin reversal agents (UHRAs) to determine their ability to block polyP procoagulant activity and also to determine their utility as antithrombotic treatments. Several UHRA compounds strongly inhibited polyP procoagulant activity in vitro, and 4 were selected for further examination in mouse models of thrombosis and hemostasis. Compounds UHRA-9 and UHRA-10 significantly reduced arterial thrombosis in mice. In mouse tail bleeding tests, administration of UHRA-9 or UHRA-10 was associated with significantly less bleeding compared with therapeutically equivalent doses of heparin. Thus, these compounds offer a new platform for developing novel antithrombotic agents that target procoagulant anionic polymers such as polyP with reduced toxicity and bleeding side effects.

材料
製品番号
ブランド
製品内容

Sigma-Aldrich
水酸化ナトリウム, ACS reagent, ≥97.0%, pellets
Sigma-Aldrich
水酸化ナトリウム, reagent grade, ≥98%, pellets (anhydrous)
Sigma-Aldrich
水酸化ナトリウム 溶液, 50% in H2O
Sigma-Aldrich
水酸化ナトリウム 溶液, BioUltra, for molecular biology, 10 M in H2O
Sigma-Aldrich
水酸化ナトリウム, BioXtra, ≥98% (acidimetric), pellets (anhydrous)
Sigma-Aldrich
水酸化ナトリウム 溶液, 1.0 N, BioReagent, suitable for cell culture
Sigma-Aldrich
水酸化ナトリウム, puriss., meets analytical specification of Ph. Eur., BP, NF, E524, 98-100.5%, pellets
Sigma-Aldrich
水酸化ナトリウム, reagent grade, 97%, powder
Sigma-Aldrich
水酸化ナトリウム, pellets, semiconductor grade, 99.99% trace metals basis
Sigma-Aldrich
水酸化ナトリウム, puriss. p.a., ACS reagent, reag. Ph. Eur., K ≤0.02%, ≥98%, pellets
Sigma-Aldrich
水酸化ナトリウム 溶液, 0.1 M
Sigma-Aldrich
水酸化ナトリウム 溶液, 5.0 M
Sigma-Aldrich
アジ化ナトリウム, BioUltra, ≥99.5% (T)
Sigma-Aldrich
水酸化ナトリウム, beads, 16-60 mesh, reagent grade, 97%
Sigma-Aldrich
アジ化ナトリウム, purum p.a., ≥99.0% (T)
Sigma-Aldrich
水酸化ナトリウム, puriss. p.a., ACS reagent, K ≤0.02%, ≥98.0% (T), pellets
Sigma-Aldrich
水酸化ナトリウム 溶液, 1 M
Sigma-Aldrich
水酸化ナトリウム, reagent grade, 97%, flakes
Sigma-Aldrich
水酸化ナトリウム, BioUltra, for luminescence, ≥98.0% (T), pellets
Sigma-Aldrich
アジ化ナトリウム, ReagentPlus®, ≥99.5%
Sigma-Aldrich
水酸化ナトリウム, JIS special grade, ≥96.0%
Sigma-Aldrich
水酸化ナトリウム, SAJ first grade, ≥95.0%
Sigma-Aldrich
水酸化ナトリウム, ultra dry, powder or crystals, 99.99% trace metals basis
Sigma-Aldrich
水酸化ナトリウム 溶液, 2 M
Sigma-Aldrich
水酸化ナトリウム 溶液, purum, ≥32%
Sigma-Aldrich
水酸化ナトリウム 溶液, 0.5 M
Sigma-Aldrich
水酸化ナトリウム 溶液, 6 M
Supelco
水酸化ナトリウム濃縮溶液, 0.1 M NaOH in water (0.1N), Eluent concentrate for IC
Sigma-Aldrich
水酸化ナトリウム 溶液, 20 % (w/v)
Sigma-Aldrich
水酸化ナトリウム 溶液, 0.2 M