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项与 Alfama, Inc. 相关的药物

Macromolecular carrier-linked carbon monoxide releasing molecules (Alfama)

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0 项与 Alfama, Inc. 相关的专利（医药）

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项与 Alfama, Inc. 相关的文献（医药）

2012-08-27·Organometallics

Generation of Carbon Monoxide Releasing Molecules (CO-RMs) as Drug Candidates for the Treatment of Acute Liver Injury: Targeting of CO-RMs to the Liver

作者: Penacho, Nuno ; Marques, Ana R. ; Otterbein, Sherrie L. ; Reis, Patrícia M. ; Matos, Marta N. De ; Kromer, Lukas ; Rodrigues, Sandra S. ; Seixas, João D. ; Gallo, David J. ; Bernardes, Gonçalo J. L. ; Ruggieri, Rachel A. ; Gonçalves, Ana M. L. ; Romão, Carlos C. ; Gonçalves, Ana S. G. ; Blättler, Walter A. ; Bento, Isabel ; Otterbein, Leo E.

Molybdenum water-soluble carbonyl isocyanide complexes were prepared as liver-targeted, potential CO-releasing mols. and tested for cytotoxicity and CO release on murine acetaminophen-induced acute liver failure model.Tricarbonyl complexes [Mo(CO)₃(CNCR¹R²CO₂R³)₃] (1, R¹, R² = H, Me, ⁱPr, Et, CH₂Ph; R¹-R² = (CH₂)₅; R³ = H, Na, Li) were found to be least toxic and still active CO-releasing agents.The synthetic procedure for preparation of 1 (R³ = H) comprises ligand substitution reaction of [Mo(CO)₃(η⁶-toluene)] with isocyanides CNCR¹R²CO₂Me, saponification with NaOH and protonation with aqueous HCl.The discovery of the biol. effects of carbon monoxide (CO) in recent years strongly suggests that CO could find applications as a therapeutic agent.CO is a highly toxic gas when used at industrial doses, due in part to its binding affinity to Hb.Since Hb binds CO with the highest affinity in vivo, it also constitutes a major barrier to the delivery of CO to tissues in need of therapy.A method of delivering CO that can bypass Hb is the use of pro-drugs or CO carriers, called CO-releasing mols. (CO-RMs) that become activated and release CO in tissues in need of treatment.Organometallic carbonyl complexes are best suited to play the role of CO carriers, and indeed the natural CO carrier mols. Hb and myoglobin belong to this class of chem. compoundsThe prepared complexes 1 present favorable druglike characteristics, have low toxicity, and demonstrate specific CO delivery to the liver in the treatment of acetaminophen (APAP)-induced acute liver failure in mice.

2010-02-02·Circulation1区 · 医学

Nitric Oxide–Dependent Bone Marrow Progenitor Mobilization by Carbon Monoxide Enhances Endothelial Repair After Vascular Injury

1区 · 医学

Article

作者: Chin, Beek Y. ; Ozanich, Brett ; Ahmed, Asif ; Baty, Catherine J. ; Gallo, David J. ; Tzeng, Edith ; Ahmad, Shakil ; Raman, Kathleen G. ; Otterbein, Leo E. ; Wegiel, Barbara ; Karlsson, Jenny M.

Background— Carbon monoxide (CO) has emerged as a vascular homeostatic molecule that prevents balloon angioplasty–induced stenosis via antiproliferative effects on vascular smooth muscle cells. The effects of CO on reendothelialization have not been evaluated. Methods and Results— Exposure to CO has diametrically opposite effects on endothelial cell (EC) and vascular smooth muscle cell proliferation in rodent models of carotid injury. In contrast to its effect of blocking vascular smooth muscle cell growth, CO administered as a gas or as a CO-releasing molecule enhances proliferation and motility of ECs in vitro by >50% versus air controls, and in vivo, it accelerates reendothelialization of the denuded artery by day 4 after injury versus day 6 in air-treated animals. CO enhanced EC proliferation via rapid activation of RhoA (Ras homolog gene family, member A), followed by downstream phosphorylation of Akt, endothelial nitric oxide (NO) synthase phosphorylation, and a 60% increase in NO generation by ECs. CO drives cell cycle progression through phosphorylation of retinoblastoma, which is dependent in part on endothelial NO synthase–generated NO. Similarly, endothelial repair in vivo requires NO-dependent mobilization of bone marrow–derived EC progenitors, and CO yielded a 4-fold increase in the number of mobilized green fluorescent protein–Tie2–positive endothelial progenitor cells versus controls, with a corresponding accelerated deposition of differentiated green fluorescent protein–Tie2–positive ECs at the site of injury. CO was ineffective in augmenting EC repair and the ensuing development of intimal hyperplasia in eNOS−/− mice. Conclusions— Collectively, the present data demonstrate that CO accelerates EC proliferation and vessel repair in a manner dependent on NO generation and enhanced recruitment of bone marrow–derived endothelial progenitor cells.

100 项与 Alfama, Inc. 相关的药物交易

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100 项与 Alfama, Inc. 相关的转化医学

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